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Author Topic: http://natap.org/  (Read 62225 times)

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Offline red_Dragon888

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http://natap.org/
« on: January 13, 2010, 07:25:22 PM »
Chloroquine To Block Immune Activation

"Chronic immune activation is a hallmark of HIV-1 pathogenesis....Our results suggests that a safe well tolerated drug such as chloroquine can be proposed as an adjuvant therapeutic candidate along with HAART to control immune activation in HIV-1 infection.....Chloroquine is widely accessible, inexpensive and is well tolerated when administered over periods of several years making it a good candidate for adjuvant therapy along with HAART to control immune activation in HIV-1 infection. The relevance of the findings presented in this study are particularly important as it is now known that non AIDS defining illnesses such as atherosclerosis, liver disease, renal diseases that occur despite effective HAART contribute to mortality. Immune activation and inflammation are the key contributing factors linked to these co-morbidities (49). The use of chloroquine as an adjuvant with HAART could be an effective and inexpensive approach to control immune activation and reduce the risk of comorbidities in HAART treated HIV infected individuals. The use of chloroquine in HIV-1 infected individuals in resource rich and resource poor countries need to be further investigated.....HIV-1 infection hijacks the innate immune response which directly contributes to disease pathogenesis. Chronic stimulation of pDC with non-infectious and infectious virions leads to their enhanced activation, state, production of the cytokine IFNα and an up-regulation of IDO and PDL-1, all of which are known to directly contribute to decreased T cell survival, proliferation, and function. In this study, we have shown that chloroquine blocks TLR signaling in pDC, a critical step in its activation pathway. By blocking pDC activation we observed a decrease in the immunoregulatory cytokine IFNα which in turn could reduce IFNα mediated immune activation and improve T cell survival by blocking negative modulators like IDO and PDL-1."


Chloroquine Modulates HIV-1 Induced Plasmacytoid Dendritic Cell IFN{alpha}: Implication for T cell Activation



Antimicrob. Agents Chemother. doi:10.1128/AAC.01246-09

published online ahead of print on 30 November 2009



Jeffrey A. Martinson, Carlos J. Montoya, Xiomara Usuga, Rollie Ronquillo, Alan L. Landay, and Seema N. Desai*




Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL-USA; Group of Immunovirology-Biogenesis, University of Antioquia, Medellin-Colombia




* To whom correspondence should be addressed. Email: Seema_N_Desai@rush.edu.



ABSTRACT
Plasmacytoid dendritic cell (pDC) mainly contribute to antiviral immunity through recognition of microbial products and viruses via intracellular toll-like receptors (TLR) 7 or 9 that results in the production of type I interferons. Though interferons reduce viral burden in acute phase of infection their role in chronic phase is unclear. Presence of elevated plasma IFN{alpha} levels in advanced HIV disease and its association with microbial translocation in chronic HIV infection lead us to hypothesize that IFN{alpha} could contribute to immune activation. Blocking IFN{alpha} production using chloroquine an endosomal inhibitor was tested in a novel in vitro model system with the aim to characterize the effects of chloroquine on HIV-1 mediated TLR signaling, IFN{alpha} production and T cell activation. Our results indicate that chloroquine blocks TLR mediated activation of pDC and MyD88 signaling as shown by decrease in the downstream signaling molecules IRAK-4, IRF-7 and inhibition of IFN{alpha} synthesis. Chloroquine decreased CD8 T cell activation induced by AT-2 HIV-1 in PBMC cultures. In addition to blocking pDC activation, chloroquine also blocked negative modulators of T cell response like IDO (indoleamine 2, 3-dioxygenase) and PDL-1 (programmed death ligand-1). Our results indicate that TLR stimulation and production of IFN-{alpha} by pDC contribute to immune activation, and blocking these pathways using chloroquine may interfere with events contributing to HIV pathogenesis. Our results suggests that a safe well tolerated drug such as chloroquine can be proposed as an adjuvant therapeutic candidate along with HAART to control immune activation in HIV-1 infection.

NATAP http://natap.org/

« Last Edit: January 13, 2010, 07:31:09 PM by red_Dragon888 »
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Offline red_Dragon888

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Re: NATAP: Update
« Reply #1 on: January 13, 2010, 07:29:01 PM »
GS-9148 Nucleotide Active Against Resistance


 "GS-9148 retained its activity against viruses with four or more TAMs, including combinations containing the M41L and L210W mutations....Viruses carrying the K65R, K70E, L74V, or M184V mutation, as well as various combinations thereof, were fully susceptible or slightly hypersensitive to GS-9148.....GS-9148 showed a minimal loss of activity against a multidrug-resistant virus containing TAMs in combination with M184V and an insertion at T69......suggesting a less effective renal transport and possibly a lower potential for nephrotoxicity than that of acyclic nucleotide analogs. Finally, quantitative studies confirmed that despite increased cellular permeation, GS-9131 at concentrations of up to 50 µM did not cause any selective depletion of mtDNA in HepG2 cells (data not shown), an observation consistent with the low potential of GS-9148 to interfere with the replication of mtDNA."


The HIV-1 RT Mutant Q151L Shows Decreased Replication Capacity, Selective High-Level Resistance to GS-9148 and Hypersusceptibility to Tenofovir and Zidovudine - (06/15/09)
GS9148: A Novel Nucleotide Active Against HIV-1 Variants with Drug ...
Feb 6, 2006 ... Preliminary pre-clinical data shows GS9148 appears potent and safe, and did not show an effect on mitochondrial DNA; was effective against ...
www.natap.org/2006/CROI/CROI_02.htm
Inefficient Renal Transport of Nucleotide Reverse Transcriptase ...
GS-9148 is a novel nucleotide HIV RT inhibitor active against a variety of ... GS-9148 showed relatively inefficient transport by the renal uptake ...
www.natap.org/2008/CROI/croi_107.htm
Novel Nucleotide Inhibitor GS-9148 Selects for a K70E Mutation in ...
GS-9148 (Fig. 1) is a novel nucleotide HIV RT inhibitor with a favorable in vitro resistance profile against HIV-1 strains with clinically relevant ...
www.natap.org/2007/ICAAC/ICAAC_28.htm




Design and Profiling of GS-9148, a Novel Nucleotide Analog Active against Nucleoside-Resistant Variants of Human Immunodeficiency Virus Type 1, and Its Orally Bioavailable Phosphonoamidate Prodrug, GS-9131



Antimicrobial Agents and Chemotherapy, February 2008

Tomas Cihlar,1* Adrian S. Ray,1 Constantine G. Boojamra,1 Lijun Zhang,1 Hon Hui,1 Genevieve Laflamme,1 Jennifer E. Vela,1 Deborah Grant,1 James Chen,1 Florence Myrick,2 Kirsten L. White,1 Ying Gao,1 Kuei-Ying Lin,1 Janet L. Douglas,1 Neil T. Parkin,3 Anne Carey,1 Rowchanak Pakdaman,1 and Richard L. Mackman1

Gilead Sciences, Foster City, California,1 Gilead Sciences, Durham, North Carolina,2 Monogram Biosciences, South San Francisco, California3




GS-9131 is an attractive clinical development candidate for the treatment of patients infected with NRTI-resistant HIV.....The discovery of the favorable resistance profile of the previously described nucleoside phosphonate d4AP (20) was an important initial step toward the design of GS-9148.....Results from a PhenoSense analysis indicate that GS-9148 meets the target resistance profile set for the development candidate by maintaining its activity against multiple patient-derived HIV strains with the major known NRTI resistance mutations. Importantly, its profile appears to be distinct from that of the clinically approved NRTIs in that GS-9148 was the only inhibitor tested that showed no reduction in potency due to K65R, L74V, and M184V mutations, together with the minimal resistance associated with multiple TAMs

ABSTRACT


GS-9148 [(5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yloxymethyl)phosphonic acid] is a novel ribose-modified human immunodeficiency virus type 1 (HIV-1) nucleotide reverse transcriptase (RT) inhibitor (NRTI) selected from a series of nucleoside phosphonate analogs for its favorable in vitro biological properties including (i) a low potential for mitochondrial toxicity, (ii) a minimal cytotoxicity in renal proximal tubule cells and other cell types, (iii) synergy in combination with other antiretrovirals, and (iv) a unique resistance profile against multiple NRTI-resistant HIV-1 strains. Notably, antiviral resistance analysis indicated that neither the K65R, L74V, or M184V RT mutation nor their combinations had any effect on the antiretroviral activity of GS-9148. Viruses carrying four or more thymidine analog mutations showed a substantially smaller change in GS-9148 activity relative to that observed with most marketed NRTIs. GS-9131, an ethylalaninyl phosphonoamidate prodrug designed to maximize the intracellular delivery of GS-9148, is a potent inhibitor of multiple subtypes of HIV-1 clinical isolates, with a mean 50% effective concentration of 37 nM. Inside cells, GS-9131 is readily hydrolyzed to GS-9148, which is further phosphorylated to its active diphosphate metabolite (A. S. Ray, J. E. Vela, C. G. Boojamra, L. Zhang, H. Hui, C. Callebaut, K. Stray, K.-Y. Lin, Y. Gao, R. L. Mackman, and T. Cihlar, Antimicrob. Agents Chemother. 52:648-654, 2008). GS-9148 diphosphate acts as a competitive inhibitor of RT with respect to dATP (Ki = 0.8 µM) and exhibits low inhibitory potency against host polymerases including DNA polymerase {gamma}. Oral administration of GS-9131 to beagle dogs at a dose of 3 mg/kg of body weight resulted in high and persistent levels of GS-9148 diphosphate in peripheral blood mononuclear cells (with a maximum intracellular concentration of >9 µM and a half-life of >24 h). This favorable preclinical profile makes GS-9131 an attractive clinical development candidate for the treatment of patients infected with NRTI-resistant HIV.




http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #2 on: January 14, 2010, 12:38:24 PM »
NATAP: Preventing Dementia -Hypertension Meds
Thu, January 14, 2010 9:42:56 AMFrom: "nataphcvhiv@natap.org" <nataphcvhiv@natap.org>Add to Contacts

--------------------------------------------------------------------------------

NATAP http://natap.org/
_______________________________________________

"This study suggests that angiotensin receptor blockers are associated with reduced incidence and progression of Alzheimer’s disease and dementia compared with other drugs for cardiovascular disease or hypertension.....As angiotensin receptor blockers and angiotensin converting enzyme inhibitors both decrease signalling through the AT1 receptor, we hypothesised that their combined use might result in added inhibition, leading to enhanced clinical efficacy......Combined use was generally associated with lower outcome rates than use of angiotensin receptor blockers alone, angiotensin converting enzyme inhibitor alone, or lisinopril alone....The additive benefits of both drug classes is consistent with recent prospective clinical trials.24 Combination therapy therefore could be particularly beneficial for patients."......"All of the patients had heart disease and were being treated either with ARBs, such as AstraZeneca's Atacand (candesartan), sanofi-aventis and Bristol-Myers Squibb's Avapro (irbesartan), Merck & Co.'s Cozaar (losartan), and Novartis' Diovan (valsartan), AstraZeneca's ACE inhibitor Zestril (lisinopril), or other cardiovascular drugs. Data from the study showed that those patients receiving ARBs were up to 24 percent less likely to develop dementia than patients taking other drugs."



Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis


Published 12 January 2010 BMJ 2010;340:b5465



Nien-Chen Li, statistician1,2, Austin Lee, senior statistician2,3, Rachel A Whitmer, research epidemiologist4, Miia Kivipelto, associate professor5, Elizabeth Lawler, epidemiologist6, Lewis E Kazis, professor1,2, Benjamin Wolozin, professor2,7




1 Center for the Assessment of Pharmaceutical Practices and Pharmaceutical Assessment, Management and Policy Program, Department of Health Policy and Management, Boston University School of Public Health, Boston, MA, USA, 2 Center for Health Quality Outcomes and Economic Research, Veteran Affairs Medical Center, Bedford, MA, 3 Department of Surgery, Massachusetts General Hospital, Boston, MA, 4 Division of Research, Epidemiology, Etiology and Prevention, Kaiser Permanente, Oakland, CA, USA, 5 Aging Research Center, Karolinska Institute, Stockholm, Sweden, 6 MAVERIC, VA Cooperative Studies Program, Boston, MA, 7 Department of Pharmacology and Department of Neurology, Boston University School of Medicine, Boston, MA 02118-2526, USA

Correspondence to: bwolozin@bu.edu
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #3 on: January 14, 2010, 12:40:42 PM »
Chloroquine To Block Immune Activation - pdf attached - (01/13/09)

Antimicrob. Agents Chemother published online ahead of print on 30 November 2009

Chloroquine for Reducing Immune Activation in HIV- Infected Individuals
This study is currently recruiting participants.
Verified by National Institute of Allergy and Infectious Diseases (NIAID), August 2009
First Received: January 8, 2009   Last Updated: November 18, 2009   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00819390

  Purpose
HIV is characterized by frequent immune system activation. Early in the course of infection the body establishes an immune activation "set point" related to the amount of HIV in the blood stream. This set point affects the rate of CD4 cell loss. Without CD4 cells, or with very low levels of CD4 cells, the body cannot fight off illness. This is known as immunodeficiency. If left untreated HIV can lead to extreme immunodeficiency and AIDS.

Evidence suggests that by decreasing the rate of immune system activation, immune deficiency progression could be prevented. The purpose of this study is to learn how well chloroquine can reduce the level of immune activation and to test the safety and tolerance of chloroquine in people infected with HIV.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #4 on: January 15, 2010, 09:22:33 PM »
Atripla (Efavirenz/Emtricitabine/Tenofovir disoproxil fumarate) Product Label Updated - updated label pdf attached

On January 7, 2010, FDA approved an updated Atripla label including new efficacy, safety and resistance data in treatment experienced patients from a trial (Study 073: A Phase IV, Open-Label, Randomized, Multicenter Study Evaluating Efficacy and Tolerability of single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir DF Compared to Unmodified HAART in HIV-1 Infected Subjects Who Have Achieved Virological Suppression on their HAART Regimen) in which HIV-1 infected adults on a stable antiretroviral regimen were either switched to Atripla or remained on their background regimen to compare the effectiveness (efficacy, safety, and tolerability) of Atripla to that of subjects continuing unmodified HAART as measured by the proportion of subjects who maintain HIV-1 RNA <200 copies/mL on their original assigned regimen at Week 48 based on the time-to-loss of virologic response (TLOVR) analysis.



Atripla label update reflects new efficacy, safety and resistance data in treatment experienced patients
 

On January 7, 2010, FDA approved an updated Atripla label including new efficacy, safety and resistance data in treatment experienced patients from a trial (Study 073: A Phase IV, Open-Label, Randomized, Multicenter Study Evaluating Efficacy and Tolerability of single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir DF Compared to Unmodified HAART in HIV-1 Infected Subjects Who Have Achieved Virological Suppression on their HAART Regimen) in which HIV-1 infected adults on a stable antiretroviral regimen were either switched to Atripla or remained on their background regimen to compare the effectiveness (efficacy, safety, and tolerability)of Atripla to that of subjects continuing unmodified HAART as measured by the proportion of subjects who maintain HIV-1 RNA <200 copies/mL on their original assigned regimen at Week 48 based on the time-to-loss of virologic response (TLOVR) analysis.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #5 on: January 16, 2010, 10:35:13 PM »
http://www.natap.org/2008/HIV/102308_01.htm

Neurotoxic effect of HIV: HIV-1 RNA concentration and cognitive ...
"The failure to identify a relationship between viral load and severity of cognitive impairment is consistent with the notion that the neurotoxic effect of ...
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #6 on: January 22, 2010, 02:50:03 PM »
HIV infection linked to aging of the brain

The study led by researchers from Washington University School of Medicine in St. Louis and the University of California-San Diego showed that blood flow in the brains of HIV patients is reduced to levels normally seen in uninfected patients 15 to 20 years older.

"The graying of the AIDS patient community makes this infection's effects on the brain a significant source of concern," said first author Dr Beau Ances, assistant professor of neurology at Washington University.

"Patients are surviving into their senior years, and a number of them are coming forward to express concerns about problems they're having with memory and other cognitive functions.

"We believe the virus crosses into the brain using infected immune cells.”Once in the brain, HIV doesn't directly infect neurons but instead affects supporting cells that can release immune factors that harm neurons," Ances added.

During the study, researchers used magnetic resonance imaging scanners and a new technique known as arterial spin labeling that allows precise, non-invasive blood flow measurement.

They recruited 26 subjects with HIV and 25 uninfected controls. When individuals were resting in the scanner, brain blood flow values were significantly reduced in subjects with HIV compared to uninfected controls.

These reductions decreased brain blood flow to levels roughly equivalent to readings seen for uninfected individuals 15 to 20 years older.

When scientists asked participants to perform a visual task, which normally triggers an increase in blood flow to particular regions of the brain involved in the task, participants with HIV had greater blood flow increases, suggesting the brain and its support systems had to work harder to get the task done.

"Brain blood flow levels decline naturally as we age, but HIV, the medications we use to control it or some combination of the two appear to be accelerating this process independent of aging," Ances added.

The study appears online in The Journal of Infectious Diseases

>>>I would like to interject that I have felt that my meds, Atripla, has lowered my mental activity.<<<
« Last Edit: January 22, 2010, 03:05:32 PM by red_Dragon888 »
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Re: http://natap.org/
« Reply #7 on: January 23, 2010, 11:07:38 AM »
Vicriviroc in Combination Therapy with an Optimized Regimen for Treatment‐Experienced Subjects: 48‐Week Results of the VICTOR‐E1 Phase 2 Trial




The Journal of Infectious Diseases Feb 15 2010;201:590–599



Jamal Suleiman,1,a Barry S. Zingman,4,a Ricardo Sobhie Diaz,2 Jose Valdez Ramalho Madruga,3 Edwin DeJesus,5 Jihad Slim,6 Carmen Mak,7 Erin Lee,7 Michael C. McCarthy,7 Lisa M. Dunkle,7 and Sharon Walmsley8




1Brasilmed Assistência Médica e Pesquisas, 2Laboratorio de Retrovirologia, Federal University of Sao Paulo, and 3Centro de Referencia e Treinamento em DST/AIDS, Sao Paulo, Brazil; 4Montefiore Medical Center and the Einstein‐Montefiore Center for AIDS Research, Bronx, New York; 5Orlando Immunology Center, Orlando, Florida; 6St Michael’s Medical Center–Infectious Diseases, Newark, 7Schering‐Plough Research Institute, Kenilworth, New Jersey; and 8The University Health Network, Toronto, Ontario, Canada



ABSTRACT


Background. Agents that block the CCR5 coreceptor for human immunodeficiency virus (HIV) have demonstrated potent antiretroviral activity. In early clinical studies, the CCR5 antagonist vicriviroc proved to be a safe and effective component of combination antiretroviral therapy.




Methods. This double‐blind, dose‐ranging, phase 2 trial randomized subjects to receive 30 mg or 20 mg of vicriviroc or placebo once daily plus re‐optimized background therapy containing a protease inhibitor with ritonavir. Subjects were adults infected with CCR5‐tropic HIV who were experiencing failure of triple antiretroviral regimens. The primary end point was mean change in baseline log10 HIV RNA level at 48 weeks, based on an intent‐to‐treat analysis.




Results. One hundred fourteen persons received vicriviroc at 30 mg (n=39), vicriviroc at 20 mg (n=40), or placebo (n=35). The mean change in baseline HIV RNA level at week 48 was −1.77 log10 copies/mL for 30 mg of vicriviroc and −1.75 log10 copies/mL for 20 mg of vicriviroc, compared with −0.79 log10 copies/mL for placebo (=.002 and , p=,003 respectively, compared with placebo). Mean CD4 counts increased by 102, 136, and 63 cells/mm3 for 30 mg vicriviroc, 20 mg vicriviroc, and placebo, respectively ( and , respectively, compared with placebo). Rates of adverse events (mostly mild‐to‐moderate) were 111.4, 112.5, and 147.4 events per 100 subject‐years, respectively.




Conclusions. Vicriviroc administered with a protease inhibitor plus ritonavir–containing regimen shows potent antiretroviral and immunologic activity sustained over 48 weeks in treatment‐experienced patients.





The life expectancy of people with human immunodeficiency virus (HIV) infection has steadily increased since the introduction of antiretroviral therapy >2 decades ago [1]. Current guidelines recommend that patients receive >3 antiretroviral drugs of at least 2 classes [2]. Although antiretroviral therapy is effective in suppressing viral replication in many patients, treatment failure is relatively frequent. Virologic failure is commonly associated with drug resistance, which often involves cross‐resistance within classes of drugs [3, 4]. Many patients discontinue initial antiretroviral therapy because of adverse effects [5]. The need to replace drugs that are no longer effective or tolerable to maintain a fully active regimen creates an ongoing demand for agents from new classes with novel mechanisms of action and favorable adverse‐effect profiles. One new class of antiretrovirals is the CCR5 antagonists. These agents block the CCR5 chemokine receptor, which most strains of HIV use as a coreceptor for gaining entry to CD4+ cells. Blockade of CCR5 has been shown to provide potent antiretroviral activity [6].




Vicriviroc is a novel, small‐molecule CCR5 antagonist, which has demonstrated potent antiviral activity in early clinical studies. As a substrate of CYP3A4, vicriviroc may be administered in regimens containing a CYP3A4 inhibitor without dosage adjustment, and clinical development (including this protocol) has taken the strategy of vicriviroc use in regimens containing a ritonavir‐boosted protease inhibitor. This approach provides the convenience of a single dose of 30 mg once daily with no adjustment required for concomitant medications. In a phase 2 trial evaluating vicriviroc in daily doses of 5, 10, and 15 mg added to a failing ritonavir‐containing regimen, antiviral activity was observed in all 3 vicriviroc dosage groups [7]. However, because it was not clear that optimal antiviral benefit had been achieved and because no dose‐limiting toxicities had been observed, testing at higher doses was deemed advisable. This trial was designed to evaluate the efficacy and safety of 2 dose levels of vicriviroc, compared with placebo, each in combination with optimized background therapy (OBT) containing a protease inhibitor with ritonavir.




Results




The study was conducted in North and Latin America, Europe, and South Africa from June 2006 through October 2007. One hundred sixteen persons were randomized to receive vicriviroc at 30 mg (n=40), vicriviroc at 20 mg (=39), and placebo (n=37). The treatment groups were balanced with respect to demographic and baseline characteristics. Consistent with other similarly designed studies reported recently, over one‐half of subjects had <2 active drugs in their OBT (Table 1).



Subject disposition.
One hundred fourteen subjects received at least 1 dose of blinded study drug (modified intent‐to‐treat population) (Table 1). On the basis of a Kaplan‐Meier analysis, time to discontinuation for any reason was significantly longer in the vicriviroc groups than in the placebo group (p=.001 and p<.0001 for the vicriviroc 30 mg and vicriviroc 20 mg arms, respectively, compared with placebo). Treatment failure, the most common reason for discontinuation, occurred most frequently in the placebo arm. Twenty‐one (95%) of 22 treatment failures occurred by week 24 regardless of treatment assignment. No subject discontinued because of treatment‐related safety or tolerability issues.




Virologic response.
The mean change in baseline HIV RNA level at week 48 was −1.77 log10 copies/mL for the vicriviroc 30 mg recipients and −1.75 log10 copies/mL for the vicriviroc 20 mg recipients; the placebo arm exhibited a mean decrease in baseline HIV RNA of −0.79 log10 copies/mL (p=.002 and p=.003, respectively, compared with placebo) (Figure 1). The superior antiviral efficacy of vicriviroc at either 30 mg or 20 mg was apparent at week 12 (p<.001 and p=.002, respectively, compared with placebo) and was sustained thereafter (Figure 1).



Analysis of week 48 secondary end points was consistent with these results. The proportions of subjects with HIV RNA levels <50 copies/mL (modified intent‐to‐treat and noncompleter equals failure population) at week 48 were 56% (22 of 39), 53% (21 of 40), and 14% (5 of 35) in the vicriviroc 30 mg, vicriviroc 20 mg, and placebo groups, respectively (p<.001 for vicriviroc 30 mg and p<.001 for vicriviroc 20 mg, compared with placebo) (Figure 2). The modified intent‐to‐treat time to loss of virologic response virologic response rates were 59% (23 of 39), 50% (20 of 40), and 26% (9 of 35) for vicriviroc 30 mg, vicriviroc 20 mg, and placebo, respectively p=.003( and p=.027 , respectively, compared with placebo). Virologic suppression (HIV RNA level <50 copies/mL) was sustained significantly longer in the vicriviroc 30 mg or 20 mg groups, compared with placebo (p=.003 and  p=.018, respectively).



The benefit of vicriviroc in regimens regardless of the number of active drugs in the background regimen is suggested by the mean change in baseline log10 HIV RNA at week 48 (Figure 3). The magnitude of virologic suppression in subjects with fewer (<2) active drugs in the OBT appeared to favor the vicriviroc 30 mg group; the proportions of subjects with week 48 HIV RNA levels <50 copies/mL (modified intent‐to‐treat time to loss of virologic response analysis) were 57%, 29%, and 17%, respectively, for vicriviroc 30 mg, vicriviroc 20 mg, and placebo. A similar tendency to superior time to loss of virologic response with vicriviroc 30 mg appeared in subjects with baseline HIV RNA levels >100,000 copies/mL (33%, 17%, and 10%, respectively) or baseline CD4 count <200 cells/mm3 (50%, 36%, and 14%, respectively). Analyses of primary and secondary efficacy end point subgroups including age, sex, race, region, baseline HIV RNA, baseline CD4 count, overall sensitivity score, and use of enfuvirtide or darunavir yielded consistent results and supported the efficacy advantage of vicriviroc 30 mg over placebo (data not shown).



Immunologic response.
Mean CD4 counts increased by 102 cells/mm3 in the vicriviroc 30 mg group, 136 cells/mm3 in the vicriviroc 20 mg group, and by 63 cells/mm3 in the placebo group, but only the difference between the 20‐mg dose group and placebo was statistically significant (p=.039), possibly because the sample size did not provide adequate statistical power to distinguish changes in CD4 counts (Figure 4).



Coreceptor tropism.
Six subjects (5%) had CXCR4 virus (dual‐mixed or X4‐only) detected at baseline before any drug exposure (3 in the vicriviroc 30 mg group, 1 in the vicriviroc 20 mg group, and 2 in the placebo group). Subsequently, 19 additional subjects (9 in the vicriviroc 30 mg group, 7 in the vicriviroc 20 mg group, and 3 in the placebo group) had detection of DM/X4 virus after receiving treatment, with 11 detectable at or before week 8. Of the 25 subjects in whom DM/X4 virus was detected, 17 (68%) met protocol‐defined criteria for virologic failure, but only 9 discontinued the study. Four subjects who received vicriviroc and had detectable DM/X4 tropic virus experienced a >50% decrease in baseline CD4 count; 3 of these 4 subjects had detectable DM/X4 tropism at baseline (before receiving any study drug). One of these subjects discontinued the study.



Resistance.
One subject (3%) in the vicriviroc 30 mg group, 4 subjects (10%) in the 20 mg group, and no subjects in the placebo group developed vicriviroc‐resistant HIV infection at the time of study discontinuation. Among the 15 subjects receiving vicriviroc who experienced virologic failure, 2 developed resistance to the single active drug in their OBT. Among subjects with 0 or 1 fully active drugs in their OBT, the 30‐mg dose of vicriviroc appeared to confer an advantage, as resistance to vicriviroc developed less frequently (1 [4.3%] of 23 in the vicriviroc 30 mg group vs 4 [19%] of 21 in the vicriviroc 20 mg group).




Safety.
The mean duration of treatment for the 114 subjects who received study drug was 44, 45, and 33 weeks for the vicriviroc 30 mg, vicriviroc 20 mg, and placebo groups, respectively. Sixty‐eight (86%) of the 79 subjects randomized to receive vicriviroc completed 48 weeks of blinded treatment, compared with only 18 (49%) of 37 subjects in the control group.




Most subjects (>90%) experienced at least one treatment‐emergent adverse event; these occurred with similar frequencies across treatment groups (95% in vicriviroc 30 mg, 98% in vicriviroc 20 mg, and 94% in placebo group). Most adverse events were mild or moderate in severity and occurred at similar frequencies across treatment groups (74% in vicriviroc 30 mg, 78% in vicriviroc 20 mg, and 74% in placebo group). The rate of adverse events was higher among subjects in the placebo group (147.4 incidents per 100 subject‐years) than in the vicriviroc 30 mg (111.4 incidents per 100 subject‐years) and 20 mg (112.5 incidents per 100 subject‐years) groups. Table 2 lists treatment‐emergent adverse events occurring in >10% of patients, adjusted for subject‐years of exposure.



The most commonly reported adverse event was diarrhea; no trend in the rates was apparent across treatment arms. The numbers of adverse events overall were too small to draw conclusions.




The proportion of subjects with severe (grade 3/4) adverse events was similar across treatment groups (21% in vicriviroc 30 mg, 20% in vicriviroc 20 mg, and 20% in placebo group). Most grade 3/4 adverse events were isolated events in a single subject. It is notable that no seizures occurred in vicriviroc recipients.




Other events of interest included malignancies, hepatotoxicity, and ischemic cardiovascular events. No confirmed malignancies were reported in either vicriviroc group during the 48‐week treatment period of this study. The number of subjects who experienced liver‐related events was similar across treatment groups (2 in vicriviroc 30 mg, 3 in vicriviroc 20 mg, and 2 in placebo group), with the rates lower in both vicriviroc arms (6.02, 8.65, and 8.93 incidents per 100 subject‐years, respectively). Elevations in liver function test results (alanine aminotransferase or aspartate aminotransferase) were generally mild (grade 1 or 2) and were evenly distributed across treatment groups; none appeared to be dose‐related. No grade 3 or 4 elevations in alanine aminotransferase or aspartate aminotransferase were observed in the vicriviroc arms, and no subjects met the criteria for drug‐induced liver injury (Hy’s law). No ischemic cardiac events were reported.




Four deaths were reported, involving the 4 subjects who discontinued the study because of to adverse events. Two of the subjects were in the placebo group; both deaths occurred 60 days after the patient discontinued the study. One death was attributed to cardiorespiratory failure in a subject with either central nervous system toxoplasmosis or central nervous system metastases from lung cancer, and the other to hypokalemia secondary to diarrhea. Two deaths were in the vicriviroc 20 mg group; 1 occurred while participating in the study and was attributed to bilateral atypical pneumonia; the other was attributed to presumed disseminated tuberculosis complicated by multiple organ failure and occurred 15 days after the end of treatment. All deaths were deemed unlikely to be related to study drug.



http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #8 on: January 27, 2010, 03:31:42 PM »
UPDATE: Diagnosis and Management of Acute HIV Infection

http://www.hivguidelines.org/GuideLine.aspx?GuideLineID=165

Note
Note: In the medical literature, as in this chapter, the terms acute HIV infection, acute retroviral syndrome, acute HIV seroconversion, and primary HIV infection are interchangeable. For consistency, the term acute HIV infection is used in these guidelines.


I. INTRODUCTION
Studies suggest that as many as 50% of HIV transmissions occur during the acute and early stage of the illness.1-5 A number of factors contribute to the increased risk for transmission during acute infection:

•Markedly increased viral load levels during acute infection (often much greater than 10 million viral copies/mm3)
•Likelihood that risky behaviors are ongoing during this period because the individual is unaware of his/her HIV status
•The nonspecific “flu-” or “mono-like” symptoms of acute HIV infection that are frequently unrecognized as an indication of HIV infection

Detection of acute HIV infection provides an opportunity to follow patients prospectively soon after infection and thereby reduce disease progression and incidence of OIs. Because patients with a recent diagnosis of HIV are more likely to reduce risk behaviors if they are linked to primary HIV care than if they are not receiving care,6 early detection may also be a critical component of preventing further transmission.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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« Reply #9 on: February 01, 2010, 08:23:43 AM »
Follow the Money: AIDS Funding and AIDS Deaths in the Bloomberg Years




A Study by Health People: Community Preventive Health Institute written by Chris Norwood



http://www.healthpeople.org/




"Summary: The massive redistribution of the city?s federal AIDS care and support funds, started by the Bloomberg Administration in early 2006, favored Manhattan to the extent that the city Department of Health allocated almost 60% of federal funds for AIDS medical care and support services to Manhattan-based agencies. As Manhattan AIDS deaths then began decreasing at twice the rate of deaths in the Bronx and Brooklyn, the other major AIDS-impacted boroughs; the significant progress that these two “outer” boroughs---which have the poorest, most minority and highest percentage of women?s AIDS cases---had shown in bringing down their AIDS deaths during the years before this funding redistribution collapsed. Overall, black and Hispanic women suffered the worst consequences of the funding and service redistribution and were clearly denied the full chance at life which is possible today with proper AIDS care.....



.....It is past time for the federal government, including investigative agencies, to completely probe the  contracting of New York City Ryan White funds......he city tried to block FOIL (Freedom of Information Law) requests for the most  basic information with responses that defied credulity.....



.....The available public record shows that the New York City Department Health and Mental Hygiene,  under Dr. Thomas Frieden, Commissioner during most of  the Bloomberg Administration, made little  effort to disguise its disdain for outer borough AIDS populations.  At one key stage after another, the  Administration would only involve Manhattan agencies and leaders in determining AIDS policy and  funding.....In 2005, when Mayor Bloomberg, on the advice of Commissioner Frieden, appointed a New York  City Commission on AIDS---to provide the Administration with “guidance” on improving NY AIDS  care and prevention---all 20 members came from Manhattan agencies or represented government.....in its clear intent to maximize AIDS funding in Manhattan, the city violated that  requirement of the City Charter.......



.......Brooklyn as a borough lost the most funding and overall now has the greatest disparity between the  number of residents who have HIV/AIDS (24.5% of the NYC total) and the number of their deaths (30.8% of the city total)......Bronx women lost the most funding and services; indeed, key Ryan White services were  so completely withdrawn from Bronx women with HIV/AIDS that by, the end of 2006, only 3% of all  Ryan White clients in the city receiving Supportive Counseling/Family Stabilization services---services specifically intended to help stabilize women with AIDS raising children---lived in the Bronx.  The result was to derail the significant progress the Bronx had been making in keeping women---and  mothers---alive......As a group, Manhattan men received the most funding and medical/support services from the funding  switch; they then had the largest decrease in deaths of any male or female group in the major AIDS  boroughs.....Treatment adherence support---namely teaching people to use their AIDS medications  correctly---was almost entirely confined to Manhattan, with 73.5% of clients  receiving this help being Manhattan residents......




.......Thousands of AIDS clients were just left without  services as de-funded programs shut down before new ones were in place. In an unprecedented act,  this disarray and disruption occurred as a direct result of an order from the New York City Health  Commissioner.  (The “carefully crafted” response, also given to the press, was that the delay occurred because the city  was developing better ways to evaluate the programs; not one piece of paper appeared in response to  FOILs to support this public claim.).....



..........Although the federal government largely allocates this money to AIDS-impacted cities  and states based on their caseload, the New York City Department of Health blatantly favored  Manhattan hospitals, clinics, social service and support agencies in contracting the AIDS services  provided with federal funds.  The city?s distribution of federal Ryan White AIDS funds directly  impacted death rates in the boroughs---and the prospects of life."........."
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #10 on: February 06, 2010, 08:03:17 AM »
TAT2, New HIV Treatment May Also Slow Aging Process\


"Across multiple assays on cells from nine individual HIV-1-infected donors, TAT2 significantly enhanced the CD8+ T lymphocyte suppression of HIV-1 replication"



"our studies indicate that telomerase activators, such as TAT2, may constitute a novel class of therapeutic agents which improve immune function at a fundamental, cellular aging level, thus complementing existing drugs for the treatment of HIV/AIDS and a variety of age-related diseases associated with immune deficiency....could be useful in treating HIV disease as well as immunodeficiency and increased susceptibility to other viral infections associated with chronic diseases or aging"



"We evaluated the effect of short-term exposure to TAT2 on PHA-activated PBMC from 21 individual adult donors, including healthy persons and HIV-infected individuals. In all cases, short-term exposure to TAT2 resulted in enhancement of telomerase activity.....Indeed, the most dramatic telomerase enhancement by TAT2 was observed in the PBMC that had the lowest levels of endogenous telomerase activity, i.e., from chronically HIV-1-infected and AIDS donors."



"Previous studies have found that people with HIV who go years without developing AIDS have killer T-cells with high telomerase activity and longer telomeres......Effros’ study found that TAT2 reduced telomere shortening, increased the ability of cells to divide, and supercharged their antiviral activity......Effros hopes that TAT2 might be used as a supplement to existing anti-retroviral drugs to boost the immune systems of those with HIV....."It is beginning to look like telomerase is doing more than just keeping telomeres from getting too short," Effros"




Antiaging Therapy with TAT2: Telomerase-Based Pharmacologic Enhancement of Antiviral Function of Human CD8+ T Lymphocytes - (06/02/09) Jnl of Immunology




http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #11 on: February 09, 2010, 08:24:36 AM »
NATAP: Neurologic Disease-Undetectable Viral Load
Mon, February 8, 2010 4:30:41 PMFrom: "nataphcvhiv@natap.org" <nataphcvhiv@natap.org>Add to

--------------------------------------------------------------------------------

NATAP http://natap.org/
_______________________________________________



Neurologic Disease Despite Undetectable Viral Load & The Use of Drugs That Penetrate Well the CSF - pdf of full article attached - (02/08/10)
Clinical Infectious Diseases March 1 2010



"We describe here 11 patients presenting with neurological symptoms in an unusual clinical and virological context, given that all had a good immune status with suppressed HIV viremia. We hypothesised that HIV RNA in the CSF was the cause of neurological symptoms for the following reasons"

"The highest drug levels in the CSF were found for indinavir, nevirapine, abacavir, maraviroc, and lamivudine"
"In conclusion, physicians should be aware of the possibility of acute HIV-associated CNS disorders even in the presence of minor neurological complaints that should prompt a CSF evaluation with the determination of viral replication and genotypic resistance testing. There is a specific need for a better understanding of the dynamics of viral replication in the CNS compartment and its consequences on potential neurological dysfunctions."
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #12 on: February 11, 2010, 06:19:07 AM »
Debio-025 Activity/Safety in 3 Studies Over 3 Years


In naives, genotype 1 and 2:


1000 mg once daily produced slightly greater than 2 log reduction in HCV RNA after 29 days in genotype 1/4 and 4 logs in genotype 2/3 but at this dose 8/18 patients receiving monotherapy had hyperbilirubinemia but not at lower dose of 600 mg:


EASL 2008: Efficacy and safety of increasing doses of the cyclophilin ...
Debio 025 at daily doses of 1000 or 60 mg demonstrates an additive anti-HCV ... Debio 025in daily doses of 200 or 600 mg in combination with PegIFNa-2 was ...
www.natap.org/2008/EASL/EASL_20.htm


In this study 400 mg monotherapy did not produce antivial activity in null-responders, using a loading dose however showed better results suggested better antiviral activity, at these doses there did not appear to be hyperbilirubinemia:


EASL 2009: EFFICACY AND SAFETY OF THE CYCLOPHILIN INHIBITOR DEBIO 025 IN ...
EFFICACY AND SAFETY OF THE CYCLOPHILIN INHIBITOR DEBIO 025 IN COMBINATION WITH PEGYLATED INTERFERON ALPHA-2A AND RIBAVIRIN IN PREVIOUSLY NULL-RESPONDER ...
www.natap.org/2009/EASL/EASL_40.htm


The cyclophilin inhibitor DEBIO-025 has a potent dual anti-HIV and anti-HCV activity in treatment-naive HIV/HCV co-infected subjects




AASLD 2006: The cyclophilin inhibitor DEBIO-025 has a potent dual anti-HIV and ...
DEBIO-025, a cyclophilin inhibitor, demonstrated strong antiviral activity in vitro against HCV1 and HIV-1. In a previous phase I study, DEBIO-025 showed ...
www.natap.org/2006/AASLD/AASLD_30.htm
In a previous phase I study, DEBIO-025 showed antiviral effect (< 1 Log10 reduction) in HIV-1-positive asymptomatic subjects treated with DEBIO-025 400 and 1200 mg daily for 10 days2. In this early study presented at AASLD 2006, Treatment-naive HIV-1 mono or HIV/HCV co-infected subjects received 1200 mg DEBIO-025 or placebo twice daily for 15 days. HCV genotypes in the 16 HIV-1/HCV co-infected subjects on active treatment were evenly distributed between genotype 1 (n=5), genotype 3 (n=6), and genotype 4 (n=5). HIV-1/HCV co-infected DEBIO-025-treated subjects experienced a significantly greater maximum HCV viral load reduction compared to placebo subjects, achieving a least squares mean of 3.6 vs. 0.7. The 3 HCV genotypes identified in the study responded well to the dose administered (Figure 2). one null-responder (genotype 4) achieved at least a 2 Log10 drop in HCV viral load during treatment. Three subjects (one of each genotype) decreased viral loads below detectable levels at treatment Day 15 (2 subjects) and Day 8 (1 subject). Total bilirubin increased by a median of 22 _mol/L (range -1 to +88) during treatment, leading to hyperbilirubinaemia in 10 subjects. A total of 4/19 (21%) subjects discontinued DEBIO-025 treatment prematurely for this reason. No increase in ALT/AST or _-GT was observed, and there were no signs of haemolysis. Bilirubin returned rapidly to baseline levels after treatment cessation. This phenomenon was not observed in previous DEBIO-025 studies at doses up to 1200 mg OD for 10 days
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #13 on: February 11, 2010, 06:31:45 AM »
NATAP HIV Highlights This Past Week


http://www.natap.org


National AIDS Treatment Advocacy Project - NATAP - HIV - AIDS ...HCV..HBV
Natap's web site is a leader in up-to-the minute HIV treatment information, covering the latest in drug development and research, comprehensive conference ...
www.natap.org/


Recent articles on HIV. Check out articles on HIV related Bone Issues and HIV and Aging.
 
 
 
 
 
 
 
  Neurologic Disease Despite Undetectable Viral Load & The Use of Drugs That Penetrate Well the CSF - pdf of full article attached - (02/08/10)
 

Effects of Tesamorelin, a Growth Hormone-Releasing Factor, in HIV-Infected Patients With Abdominal Fat Accumulation: A Randomized Placebo-Controlled Trial With a Safety Extension - pdf attached - (02/08/10)
 

HIV Brain Impairment - (02/08/10)
 

C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis - (02/08/10)
 

C-reactive protein and cardiovascular risk: more fuel to the fire - Comment - (02/08/10)
 

Addition of extended zidovudine to extended nevirapine prophylaxis reduces nevirapine resistance in infants who were HIV-infected in utero - (02/08/10)
 

Immunosupportive therapies in aging - pdf attached - (02/05/10)
 

The rate of mother-to-child HIV transmission among infants is 23 times higher for blacks than whites, the CDC reported. - (02/05/10)
 

Bone Loss in HIV+ Premenopausal Women & Fracture Risk - (02/04/10)
 

Protein in Urine Presages More Severe Problems - free full text link below - (02/04/10)
 

Hepatitis C and the Risk of Kidney Disease and Mortality in Veterans With HIV: "veterans coinfected with HCV have significantly higher rates of CKD and mortality" - (02/04/10)
 

Impairments in memory and hippocampal function in HIV-positive vs HIV-negative women (and men) - (01/29/10)
 
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #14 on: February 17, 2010, 01:20:11 PM »
NATAP: Early Immune Senescence in HIV

Current HIV/AIDS Reports
Published online: 2 February 2010
Seema Desai1 and Alan Landay1


"Activation and inflammation due to persistent infection such as HIV also provide a milieu for accelerated replicative senescence of T cells that progressively accumulate during the normal course of aging.....aging in the post-HAART era with suppressed viral replication is an outcome of activation and inflammation, and is most accurately defined as "inflamm-aging"....Whether HIV alone drives immunosenescence or if there are alternative pathways that contribute to early aging in HIV-infected individuals also remains to be examined.....more than 99% of HIV-1 particles detected in the circulation are not productively infectious virions. These noninfectious particles contribute to HIV-induced immunopathogenesis, as they activate the innate and adaptive immune system to release mediators of inflammation that are known to be associated with age-associated co-morbidities. The proof of this concept comes from data from the Strategies for Management of Antiretroviral Therapy (SMART) study, which shows elevated levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 to be associated with non-AIDS-defining co-morbidities in HAART-suppressed patients. The persistence of HIV virions, infectious or noninfectious, in the circulation results in the constant stimulation of the immune system and likely drives early senescence in HIV infection.....alterations in immune homeostatic mechanisms may lead to progressive loss of the naïve and memory T-cell pool, resulting in an imbalance in T-cell phenotypes. Altered T-cell homeostasis impairs regulatory cell function. HIV may deplete regulatory CD4+ T cells, which are normally responsible for suppressing T-cell activation and limiting the amount of inflammatory damage to tissues. Excessive production and/or accumulation of proinflammatory mediators such as TNF-α, IL-1ß, and IL-6 in HIV infection and in the elderly suggests that immune activation coupled with lack of anti-inflammatory responses likely results in accelerated aging in HIV disease....direct activation of innate immune cells by HIV and by disruption of the gastrointestinal barrier due to HIV-mediated depletion of Th-17 cells, leading to microbial translocation, could be contributing factors to activation and inflammation in the accelerated aging process."

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #15 on: February 17, 2010, 01:22:37 PM »
Certain Syringes More Likely To Spread Hepatitis C Virus Among Drug Users

Published: February 15, 2010

http://opa.yale.edu

New Haven, Conn. — A Yale School of Medicine study reveals that the high prevalence of the hepatitis C virus (HCV) among injection drug users may be partly due to the resilience of the virus in certain types of syringes. The study, which could open new avenues in preventing the spread of HCV, will be the focus of a presentation and press conference at the 17th Conference of Retroviruses and Opportunistic Infections on Friday, February 19, 2010 at the Moscone Center West in San Francisco.

This is believed to be the first study establishing the survival of HCV in contaminated syringes and the duration of potential infectiousness. HCV is transmitted through blood-to-blood contact. There is currently no vaccine against HCV, and treatments are problematic because of limited efficacy, high cost and side effects. Untreated, HCV can cause severe liver disease and even death. HCV infection from people sharing contaminated syringes is one of the most common and predictable consequences of injection drug use.

The Yale team simulated the most common scenarios of injection drug use in order to measure the longevity of the residual virus-blood mixture left in syringes after injection. After loading blood spiked with HCV into various syringes and depressing their plungers, researchers tested the residual blood for the presence of infective HCV immediately and after storage for up nine weeks.


They observed a prolonged survival of HCV infection at all storage temperatures, with viable amounts measured even at nine weeks in tuberculin syringes that have detachable needles. They observed far less viable HCV in insulin syringes with attached needles.
“This tells us that syringes with detachable needles are the most dangerous in terms of potential HCV infection, because they are far more likely to transmit a surviving virus,” said lead author Elijah Paintsil, M.D., assistant professor of pediatrics and pharmacology at Yale School of Medicine.




The finding of prolonged HCV survival in detachable-needle syringes has greatest implication outside of the Untied States, where use of these syringes is more common. But it also has major health implications for cities and towns everywhere, including the U.S., that offer needle-exchange programs. “These programs often stress the importance of providing injection drug users with syringes that meet their needs,” Paintsil said. “Our findings suggest that if the goal is to reduce HCV transmission, these programs should discourage use of detachable-needle syringes.”




Other authors are Huijie He, Christopher Peters, Brett D. Lindenbach and Robert Heimer of Yale School of Medicine. This study was funded by grants from the National Institutes of Health, including a Clinical Translational Science Award (CTSA) Grant from the National Center for Research Resources
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #16 on: February 17, 2010, 01:26:05 PM »
ICE CREAM COMPOUND MAY PREVENT HIV/AIDS

University of Minnesota researchers have identified a devalue that, practical vaginally, can forestall delivery of a monkey chronicle of HIV. While a not a heal as well as a devalue still contingency go by tellurian clinical trials prior to it used to forestall HIV a investigate is a outrageous step toward impediment of a harmful mildew which impacts 33 million people around a globe. For more, see: www.ahc.umn.edu/gml

http://heathpage.com/ice-cream-compound-may-prevent-hivaids/
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #17 on: February 17, 2010, 01:34:21 PM »
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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« Reply #18 on: February 17, 2010, 02:58:18 PM »
Stem cells to stem HIV
February 16, 2010 , Posted by Vignesh at 6:14 PM


http://medicalmicro.blogspot.com/2010/02/stem-cells-to-stem-hiv.html

In a study published in PLoS One, scientists from the UCLA AIDS Institute and colleagues have demonstrated that human blood stem cells can be engineered into cells that can target and kill HIV-infected cells. The good news is that, this process could potentially be used to combat other chronic viral diseases as well.


In this proof-of-principle study, it has been demonstrated that this type of approach can be used to engineer the human immune system, particularly the T-cell response, to specifically target HIV-infected cells. The researchers have identified the T-cell receptor molecules from the CD8 cytotoxic T lymphocytes, which guide the T cell in recognizing and killing HIV-infected cells. Since not enough of these cells exist to clear the virus from the body, the researchers cloned the receptor and genetically engineered human blood stem cells, then placed the stem cells into human thymus tissue that had been implanted in mice. The engineered stem cells developed into a large population of mature, multifunctional HIV-specific CD8 cells that could specifically target cells containing HIV proteins.


Based on the encouraging results, the scientists are optimistic that this approach could be a breakthrough in combating HIV and other chronic viral infections and further studies based on this approach are in pipeline.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline MBK

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Re: http://natap.org/
« Reply #19 on: February 17, 2010, 02:59:10 PM »
(in response to your youtube video) It's not a cure. It iis a drug replacement. It does not deal with archived viruses/reservoir. It might be less toxic than ARV (we'll have to see) and we might be able to ward off the possibility of having a mutant strain (we'll have to see too). But it is not a cure... :-)

Offline red_Dragon888

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« Reply #20 on: February 17, 2010, 03:02:02 PM »
http://aids.4h5.net/scientists-employ-mango-mushroom-to-beat-cancer/

Scientists employ mango, mushroom to beat cancer

CAN meals rich in mangoes and edible mushroom help to prevent or/and stop the spread of cancers? Mangoes and mushrooms have been discovered to contain ingredients that could be used for the production of new drugs for the treatment of cancers.

Scientists have discovered how a promising cancer drug, first discovered in a wild mushroom, works. The University of Nottingham, United Kingdom, team believe their work could help make the drug more effective, and useful for treating a wider range of cancers.

Cordycepin, commonly used in Chinese medicine, was originally extracted from a rare kind of parasitic mushroom that grows on caterpillars. The study appeared in the Journal of Biological Chemistry.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #21 on: February 17, 2010, 03:07:03 PM »
(in response to your youtube video) It's not a cure. It iis a drug replacement. It does not deal with archived viruses/reservoir. It might be less toxic than ARV (we'll have to see) and we might be able to ward off the possibility of having a mutant strain (we'll have to see too). But it is not a cure... :-)

I am just putting it out there, also it is last years info.  thanks for the reply.  ;)
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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« Reply #22 on: February 18, 2010, 01:16:19 PM »
QUAD Four-in-One Pill as Strong as Atripla, But a Kidney Concern Arises

17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco

Mark Mascolini

A once-daily antiretroviral combining the integrase inhibitor elvitegravir with a non-ritonavir booster (GS-9350), tenofovir (TDF), and emtricitabine (FTC) proved as potent at Atripla (efavirenz plus TDF/FTC) after 24 weeks in previously untreated people [1].

This small double-blind, double-dummy phase 2 trial found substantially fewer overall side effects with the four-in-one pill (called Quad) than with Atripla. But presenter Calvin Cohen devoted a goodly number of slides to addressing potential concerns about nephrotoxicity with GS-9350. Kidney trouble with GS-9350 would be a blow to Quad development because of TDF's well-known effect on creatinine clearance. But Cohen maintained the impact of GS-9350 on creatinine approximates that of an over-the-counter ulcer drug....

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« Reply #23 on: February 19, 2010, 10:24:05 AM »
Raltegravir Metabolics Study 96 Weeks - see attached full poster report

Conclusions

• At Week 96, both the RAL and EFV regimens demonstrated modest effects on serum lipids and glucose.

– The mean changes from baseline in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride concentrations were significantly smaller for RAL than for EFV recipients.

– The change in the total cholesterol/HDL-cholesterol ratio was not significantly different between the treatment groups.

• At week 96, DEXA showed small gains in body fat in both treatment groups.

• Longer-term experience with RAL suggests a favorable metabolic profile associated with minimal changes in body composition in treatment-naïve patients.
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« Reply #24 on: February 19, 2010, 10:26:32 AM »
HIV Load Tied to Fibrosis Signal in Women Without Hepatitis or Alcohol Abuse
17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco

Mark Mascolini

Higher HIV load correlated with a higher FIB-4 fibrosis index in HIV-infected nonalcoholic women without hepatitis virus infection or antiretroviral experience, according to results of a 1227-woman analysis of the HIV Epidemiologic Research Study (HERS) [1].

HERS is a natural history study of HIV infection in US women that ran from 1993 through 2000. This fibrosis analysis involved four groups of women--196 infected only with hepatitis C virus (HCV), 320 infected only with HIV, 498 infected with both viruses, and 213 with neither infection. The investigators also assessed another 72 women infected only with HIV who were negative for hepatitis B surface antigen and HCV, never took antiretrovirals, and reported no alcohol use in the past 6 months.

The study relied on the FIB-4 scale, a composite fibrosis indicator including age, alanine aminotransferase, aspartate aminotransferase, and platelet count. Earlier research determined that a FIB-4 below 1.45 generally means a person does not have advanced fibrosis, while a FIB-4 above 3.5 suggests advanced fibrosis [2].

In HERS women, median FIB-4 was lowest in those not infected with HIV or HCV (0.60), higher and similar in HCV-monoinfected women (0.83) and HIV-monoinfected women (0.86), and highest in HIV/HCV-coinfected women (1.30). The 72 antiretroviral-naive women with HIV but without HCV or HBV had a median FIB-4 of 0.93, similar to the larger HIV-monoinfected group. A small minority of women had a FIB-4 above the suggested fibrosis cutoff of 3.5, with the highest prevalence in coinfected women (8.6%), followed by HCV-monoinfected women (4.6%), and HIV-monoinfected women (1.3%).

Multivariate analysis determined that albumin and CD4 count had a significant negative association with FIB-4 score in HIV-monoinfected women and HIV/HCV-coinfected women, but not in HCV-monoinfected women or uninfected women.

HIV-monoinfected women

·      Albumin: r = -0.188, P = 0.0007

·      CD4 count: r = -0.401, P < 0.0001

HIV/HCV-coinfected women

·      Albumin: r = -0.235, P < 0.0001

·      CD4 count: r = -0.332, P < 0.0001

In univariate analyses, higher viral load correlated positively with higher FIB-4 score in HIV/HCV-coinfected women (r = 0.177, P < 0.001), HIV-monoinfected women (r = 0.207, P = 0.0002), and alcohol-abstaining, antiretroviral-naive, HIV-monoinfected women without HBV or HCV (r = 0.202, P = 0.03).

Although the viral load associations with FIB-4 score did not hold up in multivariate analysis, the investigators propose that the correlations suggest "a potential relationship between HIV and hepatic fibrosis in vivo." That suggestion is especially compelling in the monoinfected women with no antiretroviral experience, no exposure to HBV or HCV, and no recent alcohol use. Although higher viral load may not independently correlate with higher FIB-4 in those women, the viral load risk is not confounded by alcohol, hepatitis, or antiretroviral hepatotoxicity.

References
1. Blackard J, Welge J, Taylor L, et al.  HIV mono-infection is associated with a non-invasive index of liver fibrosis in women. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 681.
2. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317-1325.
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« Reply #25 on: February 20, 2010, 10:30:20 AM »
Gene Therapy Shows Promise Against HIV

Early findings suggest it could work, but application remains years away

By Randy Dotinga

FRIDAY, Feb. 19 (HealthDay News) -- A new study is among the first to hint that gene therapy could become a weapon against the virus that causes AIDS.

However, any treatment remains far from being ready for use by patients, and would likely be expensive, experts said.

Still, the research is "a step in the direction of using gene therapy" to treat HIV patients, said Dr. Pablo Tebas, co-author of a new study and associate professor of medicine at the University of Pennsylvania.

Existing AIDS drugs allow many patients to live fairly normal lives despite being infected with HIV. But they can cause a variety of side effects, and some patients become immune to them over time.

"The next big challenge is going to be: Can you cure the infection or control it to a level that allows patients to not take these expensive and complex medications that can be toxic?" Tebas said.

One possible solution is to help the body fight off HIV without the use of drugs. That's where gene therapy comes in, Tebas said. "Can you make the patient resistant so they can control HIV on their own?"

In the new study, the Pennsylvania team tested a gene therapy approach in which scientists first remove immune cells from patients, tinker with their genes and then put them back into the bodies of the patients.

Eight HIV-infected people took part in the study. After the genetically modified cells were placed back into the patients, "we stopped HIV treatment and tried to see what happened," Tebas said.

The findings are scheduled to be reported this week at the Conference on Retroviruses and Opportunistic Infections in San Francisco.

The levels of HIV fell below the expected levels in seven of the eight patients, the team found. Signs of the virus disappeared altogether in one patient, although that happens sometimes -- it's not an indication that the disease is cured -- and the researchers aren't sure why it happened in this case.

"We need to understand why it happened and see if we can reproduce that in the general population," Tebas said.

It's still early in the development of the treatment: the current research is in phase 2 of the customary three phases of research that new medical treatments go through.

If gene therapy does become a treatment for HIV patients, it may be best for those who aren't doing well on existing antiretroviral drugs, said John Rossi, chairman of the molecular and cellular biology department at the Beckman Research Institute of City of Hope Medical Center near Los Angeles.

"There are thousands of people who are completely resistant to all the drugs that are out there, and this is one more option they could have," Rossi said.

But the cost of the treatment would probably be high, he added, perhaps reaching around $20,000. And it's not clear how long the treatment would last, he said, since the immune cells aren't permanent.

More information

There's more on gene therapy for another condition, cancer, at the U.S. National Cancer Institute.

SOURCES: Pablo Tebas, M.D., associate professor, medicine, University of Pennsylvania, Philadelphia; John Rossi, Ph.D., chairman, department of molecular and cellular biology, Beckman Research Institute of City of Hope National Medical Center, Duarte, Calif.; presentation, Feb. 18, 2010, Conference on Retroviruses and Opportunistic Infections, San Francisco
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« Reply #26 on: February 22, 2010, 10:30:20 AM »
Discovery of Potent HIV-1 Capsid Assembly Inhibitors - see attached slide presentation

Reported by Jules Levin, 17th CROI, Feb 16-19 2010 SF

from Jules: there was very little in the way of new drug discovery presented at CROI regarding new targets. The GSK integrase & the Gilead integrase programs are moving ahead, Tobira updated on their CCR5. Tibotec has TMC278 development ongoing.
Steve Titolo1, Jean-François Mercier1, Elizabeth Wardrop1, Utavon Schwedler3, Nathalie Goudreau2, Chris Lemke2, Anne-Marie Faucher2, ChristianeYoakim2, Bruno Simoneau2, Wesley I. Sundquist3, Stephen Mason1

Boehringer Ingelheim (Canada) Ltd. Research & Development, Laval, Québec, Canada: 1Departments of Biological Sciences and 2Chemistry; 3Biochemistry Department, University of Utah, Salt Lake City, Utah, U.S.A.

Mason said “Assembly & stability of the capsid core is absolutely essential for HIV infectivity….in the presence of inhibitors the formation of the complexes is prevented….several hits were obtained….two chemotypes of advanced leads were identified that potently inhibit capsid assembly, with 2 different modes of action….mode of action is consistent with inhibition of capsid assembly….inhibitors are active in very late phase of viral replication which is also consistent with an effect on capsid assembly and viral replication….resistance mutations may indicate high genetic barrier to resistance….lead optimization was terminated, inihibition of capsid assembly is a potential viable approach for antiretroviral intervention”

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« Reply #27 on: February 22, 2010, 10:32:13 AM »
Safety and Efficacy of TBR-652, a Chemokine Receptor 5 (CCR5) Antagonist, in HIV-1-Infected, Antiretroviral (ARV) Treatment-Experienced, CCR5 Antagonist-Naïve Patients - see attached full slide presentation

 Reported by Jules Levin

17thCROI, San Francisco, February 16-19, 2010

Calvin Cohen, MD*

Research DirectorCommunity Research Initiative of New EnglandHarvard Medical School

*On behalf of TBR-652-2-201 Study Team

from Jules: this CCR5 drug has a potentially unique characteristic in that it also binds CCR2 which appears to have potentially a clinically anti-inflammatory effect. The company will explore this in future studies. In the last attachedslide you can see the binding inhibition of  drug to MCP-1 which is a reflection of its anti-inflammatory affect.

CONCLUSIONS
TBR-652 is a potent inhibitor of CCR5-tropic, HIV-1 replication
- Median nadir response up to -1.8 log10
TBR-652 demonstrated potent CCR2 activity
Generally safe and well tolerated during short-term use
- No study drug–related discontinuations, SAEs or deaths
- No clinically significant trends in AEs, laboratory, vital signs, or ECGs
- Favorable and predictable pharmacokinetic profile*
TBR-652 warrants further investigation as an unboosted, once-daily, oral CCR5 antagonist with potentially important anti-inflammatory effects
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« Reply #28 on: February 22, 2010, 10:34:47 AM »
T-cell Senescence and T-cel Activation Predict Carotid Atherosclerosis in HIV-infected Women
*******NATAP CROI POSTER OF THE YEAR 2010******


Reported by Jules Levin, CROI 2010 Feb 16-19 SF

Robert C Kaplan1, PhD, Elizabeth Sinclair2, PhD, Alan L Landay3, PhD, Nell Lurain3, PhD, Stephen J Gange4, PhD, Richey Sharrett4, MD, DrPH, Xiaonan Xue1, PhD, Peter Hunt2, MD, Howard N Hodis5, MD, Steven g Deeks,2, MD

Affiliations: 1Albert Einstein College of medicine, 2Univ of California-SF, 3Rush University Medical Center, 4Johns Hopkins Bloomberg School og Public Health, 5Univ of Southern California

Conclusions

Collectively, these observations are consistent with a model in which untreated HIV infection results in immune activation, accelerated immunologic aging and the emergence of a population of potentially dysfunctional immunosenescent T cells. Antiretroviral therapy-mediated suppression of HIV replication may only partially reverse or prevent this process. The presence of a large population of activated and/or senescent T cells may be causally associated with the premature onset of CVD.

SUMMARY OF RESULTS/DISCUSSION

- Consistent with prior data, HIV infection was associated with markedly elevated levels of activated (CD38+HLA-DR+) peripheral T-cells. Viremic suppression through effective antiretroviral therapy appeared to reduce but not completely reverse this process.

- Among HIV-infected women, T-cell activation was associated with markers of subclinical carotid artery disease after adjustment for multiple confounders.

- Among HIV-infected women, CD8+ T-cell senescence, and to a lesser extent CD4+ T-cell senescence (phenotypically defined by absence of CD28 and presence of CD57), were also associated with HIV disease and with the presence subclinical carotid artery disease.

- These associations of T-cell activation and senescence with carotid artery parameters were not observed in a population of HIV-uninfected controls who were studied using identical methods and who had comparable cardiovascular risk factor profiles. Relatively small sample size of the HIV-uninfected group is a limitation.
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« Reply #29 on: February 22, 2010, 10:41:53 AM »
Maraviroc Levels in Cerebrospinal Fluid (CSF) and Seminal Plasma from HIV-Infected Patients
Reported by Jules Levin
CROI 2010 Feb 16-20 SF

Juan Manuel Tiraboschi, J Curto, J Niubo, and D Podzamczer
Hosp Univ de Bellvitge, Barcelona, Spain

Background:  Several studies have shown that penetration of ARV drugs into reservoirs may be associated with a decreased viral replication and clinical benefit. The aim of our study was determine Maraviroc levels in CSF and semen of a group of  HIV-infected patients

Methods:  Twelve CCR5+ HIV-1 adult antiretroviral-experienced patients receiving MVC-containing regimens for at least 1 month were  enrolled. Both CSF and semen plus a blood sample were taken around 12 hours after the last MVC dose. Liquid chromatography tandem mass spectrometry (Tandem Labs, NJ, US) was used to determine MVC levels. HIV-1 viral load  was determined by real time PCR, Abbott (detection limit 40 copies/mL).

Results:  A total of 12 plasma samples, 12 CSF samples, and 9 semen samples were collected. Median CD4 count was 281 cells/uL (120 to 759) and the median HIV-1 viral load at the screening was <40 copies/mL. The median time on Maraviroc was 13.5 (4 to 60) weeks. Raltegravir was part of the background regimen in 92%, darunavir in 62% and etravirine in 42% of the patients. Nucleoside analogues were given in only one case.

Conclusions:  MVC achieves levels in CSF within the range of IC50 or higher. Thus, MVC may be of benefit in patients with HIV neurological disorders. In semen, MVC exceeds several times the IC50. However, viral replication in semen may be observed despite virological suppression in plasma, suggesting semen may act as a dinstinct compartment. Most patients with undetectable plasma viral load while receiving nucleoside-sparing regimens, including new drugs, had viral suppression in reservoirs.
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« Reply #30 on: February 22, 2010, 10:43:33 AM »
Vitamin D Deficiency and Bacterial Vaginosis among HIV-infected and -uninfected Women in the United States

Audrey French1,2, O Adeyemi1,2, D Agniel2, M Yin3, K Anastos4, and M Cohen1,2
1Rush Univ Med Ctr, Chicago, IL, US; 2CORE Ctr, Stroger Hosp of Cook County, Chicago, IL, US; 3Columbia Univ Med Ctr, New York, NY, US; and4Montefiore Med Ctr, Bronx, NY, US

Background:  Bacterial vaginosis (BV), the most frequent cause of vaginitis, is associated with morbidities such as premature labor and increased susceptibility to HIV. Recently an association between vitamin D deficiency (VDD) and BV was identified in pregnant women. We sought to replicate this finding in the Women’s Interagency HIV Study (WIHS).

Method:  A cross-sectional study of women participating in the WIHS, a longitudinal study of women with and at risk for HIV. Women in this substudy were from Chicago or New York. BV was defined by the Amsel criteria. VDD was defined as 25 (OH) D ≤20 ng/mL and insufficiency as >20 and ≤30 ng/mL.

Results:  Among 609 women studied (6 of whom were pregnant), BV was found in 19% (table). VDD was found in 60% and insufficiency in 23.5%. VDD was associated with black race, 268 of 397 vs 59 of 92 for whites, OR 3.16 (95%CI, 2.06 to 4.89), but not with HIV status, CD4, or age. Vitamin D level strongly correlated with BV (r= –0.14, P <0.001) and there was a dose response relationship; BV was most likely in women with VDD (OR 3.55), then women with insufficient levels (OR 2.12) compared with sufficient vitamin D. In multivariate analysis black race, AOR 6.03, VDD, AOR 2.46, and number of sex partners, AOR 1.54, were independently associated with BV.

Conclusions:  In this study of 609 HIV-infected and -uninfected women, BV and VDD were common and significantly correlated. VDD may partially explain the relationship between black race and BV and may be a modifiable risk factor for the disorder. Further study is needed to determine whether repletion of vitamin D will decrease the occurrence of BV.

Vitamin D and HIV-related Complications and HIV Disease Progression in Women in Tanzania



Saurabh Mehta1, D Spiegelman1, F Mugusi2, E Giovannucci1, G Msamanga2, and W Fawzi1

1Harvard Sch of Publ Hlth, Boston, MA, US and 2Muhimbili Univ of Hlth and Allied Sci, Dar es Salaam, Tanzania

Background:  Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune function. However, this relationship has not been examined in large studies or in resource-limited settings.
Methods:  Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV disease progression and related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes.


Results:  Women with low vitamin D status (serum 25-hydroxyvitamin D <32 ng/mL) had 45% higher risk of reaching a body mass index <18 kg/m2 during the first 2 years of follow-up, compared to women with adequate vitamin D levels (incidence rate ratio, RR:  1.45; 95%CI 1.04 to 2.01). The relationship between continuous vitamin D levels and risk of body mass index <18 kg/m2 during follow-up was inverse and linear (P=0.03; Figure 1). Low vitamin D status was associated with a 25% higher risk of progression to WHO HIV disease stage III or IV during follow-up (RR:  1.25; 1.05 to 1.50), compared to adequate vitamin D status. This risk decreased with increasing vitamin D levels linearly (P =0.05; Figure 2). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (RR: 1.28, 1.05 to 1.55) and thrush (RR:  2.92, 1.43 to 5.96) diagnosed during the first 2 years of follow-up. Women in the lowest vitamin D quintiles had higher incidence of mouth and throat ulcers, painful tongue or mouth, difficult or painful swallowing, diarrhea, and fatigue during the first 2 years of follow-up.


Connclusions:  Vitamin D status has a protective association with HIV disease progression and HIV-related complications during follow-up in HIV-infected women. If confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to prolong the time to ART initiation in HIV-infected patients and improve health and quality of life, particularly in resource-limited settings.
« Last Edit: February 22, 2010, 10:47:09 AM by red_Dragon888 »
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« Reply #31 on: February 22, 2010, 10:49:03 AM »
T-Cell Activation and Senescence Linked to Carotid Lesions in HIV+ Women

from Jules: this appears to me to be THE POSTER of CROI because it's the first connection between a clinical comorbidity outcome & senescence. The findings were in a relatively more advanced patient population so a key question is if you look at patients with high CD4s of say 650 and treat them with HAART will you see similar correlation with senescence; my guess is yes, senescence occurs as a result of activation & inflammation which is ongoing at some level regardless of CD4 count & undetectable viral load due to the presence of virus, HIV, regardless of whether its low or high virus levels. Perhaps the degree of senescence is less if CD4 is high & viral load low but thisT is one of many studies that need to be conducted but I think yes you will still find senescence, maybe not as often or as much but it appears HIV causes senescence.
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« Reply #32 on: February 22, 2010, 04:09:29 PM »
Man Appears To Be Cured Of HIV After Stem Cell Transplant
http://www.queeried.com/potential-hiv-cure/

Following a stem transplant from a donor carring a gene mutuation that provides natural resistance to HIV  a 42 year old man who has leukaemia now appears to have no detectable HIV in his blood.

A report on the stem cell  transplant in the New England Journal of Medicine says that since  it has occurred the patient has not tested positive for HIV, with the Dr. Gero Hutter of Charite Universitatsmedizin Berlin in Germany confirming:

“Today, two years after his transplantation, he is still without any signs of HIV disease and without antiretroviral medication.”

Performed in Germany on an American, the transplant was performed not to treat the HIV, but the man’s leukemia, however they did deliberately chose the donor with the naturally occurring gene mutation that confers resistance to HIV. Causing the resistance via a mutation (CCR5 delta32) which cripples the CCR5 receptor on the surface of T cells, that is normally attacked by HIV, this is a mutuation found only in 1 percent to 3 percent of white populations of European descent. Some people only have one copy of CCR5 delta32 which results in them taking longer to get sick or develop AIDS if infected with HIV.  If they however have two ( a copy from each parent) then they may not become infected at all.

The patient in this case was given a transplatn with two copies of  CCR5 delta32 and whilst his findings are very promising, the reality according to  Dr. Jay Levy, a professor at the University of California San Francisco, is that it won’t help the majority as the treatment is too extreme to be used as a routine treatment. He also believes that the transplant won’t have completely cured the patient as it is likely the HIV may infect other cells and resurface at a later time. Whilst this may be true, it is important to note  that the patient was also found to be infected with low levels of a type of HIV known as X4 that does not require the CCR5 receptor before the surgery , but these have shown no sign of developing.

Admitting they had no real explanation for what has happened, Hutter said the “… finding is very surprising.”, however he has agreed with other researchers that it shouldn’t be used to treat HIV alone, with Levy suggesting  “A more logical — and potentially safer — approach would be to develop some type of CCR5-disabling gene therapy or treatment that could be directly injected into the body”.
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« Reply #33 on: February 26, 2010, 10:30:56 AM »
Positive HBV Vaccine Response Halves HIV Progression and Death Risk in US Military

17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco

Mark Mascolini

A positive response to hepatitis B virus (HBV) vaccination approximately halved the risk of HIV disease progression or death in members of the US Military HIV Natural History Study, regardless of antiretroviral exposure or CD4 count [1]. The results underline the critical importance of HBV vaccination among people infected with HIV.

In addition, Michael Landrum and colleagues suggested, "HBV vaccine response may serve as a useful indicator for studying immunological correlates of HIV-related disease progression that are independent of the HIV RNA load or level of immune deficiency reflected by the CD4 count."
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« Reply #34 on: February 26, 2010, 10:33:04 AM »
Cell Studies Point to Antiinflammatory Activity of Maraviroc

17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco

Mark Mascolini

Data from clinical trials presented at the Conference on Retroviruses suggested that the CCR5 antagonists maraviroc [1] and vicriviroc [2] hold no special advantage over other antiretrovirals in pumping up CD4 counts--results deflating expectation based on earlier research, although previous studies have reported higher CD4 increases associated with maraviroc. Poor results in two phase 3 vicriviroc trials [2] led Merck to suspend development of that drug for antiretroviral-experienced people, (from Jules: as they were unable to find in the overall study a benefit with vicriviroc in patients receiving 3 or more active ARTs in the background regimen but for patients with 2 active drugs or less vicriviroc does provide benefit and this is an issue in trying to design studies for new drugs in highly treatment-experienced patients).
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« Reply #35 on: February 26, 2010, 10:33:55 AM »
Elvucitabine Versus 3TC in First-Line Regimens for 96 Weeks – see slides from poster in attached report



17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco

Mark Mascolini

Elvucitabine, a cytosine nucleoside analog, proved virologically equivalent to lamivudine (3TC) when combined with efavirenz and tenofovir as a first-line regimen taken for 96 weeks [1]. However, because of the small size of this phase 2 trial and the high dropout rate, elvucitabine lagged 3TC in a noncompleter-equals-failure virologic analysis, so further study will be needed to get a better fix on where elvucitabine may fit in treatment planning.

Elvucitabine has a half-life of about 100 hours and an in vitro 50% effective concentration of 1.1 ng/mL, suggesting 3 to 4 times greater antiviral activity than 3TC, according to Edwin DeJesus and collaborators. This double-blind trial at 16 US sites and three in India recruited 77 antiretroviral-naive people and randomized them take 10 mg of elvucitabine once daily or standard-dose 3TC plus efavirenz and tenofovir. All study participants had a CD4 count between 200 and 500, so the trial did not include people with relatively advanced HIV infection.
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« Reply #36 on: February 26, 2010, 10:36:10 AM »
FDA: Invirase, Norvir combination may increase risk for heart abnormalities

by Lianne Dane

February 23, 2010

The FDA on Tuesday announced that a review of preliminary data suggests that the combination of Roche's Invirase (saquinavir) and Abbott's Norvir (ritonavir) for the treatment of patients with HIV could cause abnormal heart rhythms in some patients.


Data submitted by Roche suggest that when the two drugs are used in combination, they can produce dose-dependent changes in the QT and PR intervals on an electrocardiogram, the FDA stated. These changes may lead to heart abnormalities that can cause patients to experience lightheadedness, fainting or irregular heart rhythms, that could, in some cases, progress to ventricular fibrillation.


The agency also noted that the risk of heart abnormalities could be higher in patients who are using other medications known to cause QT interval prolongation, and in those patients who have a history of this disturbance.


The drugmaker provided the findings in response to a prior request from the agency for all manufacturers of protease inhibitors to study the effect of these drugs on heart rhythms. Tara Cooper, a spokeswoman for Roche's Genentech unit, said "we continue to monitor and report to FDA adverse event reports from patients and physicians." She added that the FDA is currently reviewing new labelling for the drug.
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« Reply #37 on: February 26, 2010, 10:37:12 AM »
Low CD4 Nadir Predicts Neurocognitive Problems Despite Good CD4 Gains

17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco

Mark Mascolini

Neurocognitive problems persisted in many HIV-infected US residents despite good CD4 gains after starting antiretroviral therapy [1]. People whose lowest-ever (nadir) CD4 count never slipped below 350 had the best chance of averting neurocognitive problems. Those conclusions emerged from a 1525-person analysis of the prospective US CHARTER cohort, inspiring the investigators to "emphasize the importance of identifying HIV-seropositive subjects early in the course of their illness to prevent later complications."
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« Reply #38 on: February 28, 2010, 10:28:32 AM »
House of Rep Resolution on HIV Aging




HRES 1100 IH

111th CONGRESS

2d Session

H. RES. 1100

Expressing the sense of the House of Representatives that the National Institutes of Health and the Centers for Disease Control and Prevention should expand and intensify programs of research and related activities regarding the population of older individuals living with or at risk for HIV.

IN THE HOUSE OF REPRESENTATIVES

February 23, 2010

Mr. CARSON of Indiana submitted the following resolution; which was referred to the Committee on Energy and Commerce

______________________________
__

RESOLUTION

Expressing the sense of the House of Representatives that the National Institutes of Health and the Centers for Disease Control and Prevention should expand and intensify programs of research and related activities regarding the population of older individuals living with or at risk for HIV.

Whereas from 2006 through 2007, newly diagnosed cases of HIV increased 25 percent among individuals over the age of 50;

Whereas since 2003, the number of women 50 years of age and older who have been newly diagnosed with HIV has increased 40 percent;

Whereas individuals over the age of 50 made up 15 percent of newly diagnosed cases of HIV in 2007 and almost 17 percent in the first half of 2008;

Whereas the number of older individuals with HIV is expected to increase substantially by 2015, with half of all individuals with HIV in the United States being over the age of 50;

Whereas few physicians are taught to start conversations with their elderly patients about sex or HIV education and are less likely to offer testing to older individuals;

Whereas the number of newly diagnosed HIV infections in older adults was 12 times higher among Blacks and 5 times higher among Latinos than Whites;

Whereas data collection should include an emphasis on breaking down age groups, tracking risk factors for infection for older adults, and behavioral data so the National Institutes of Health can better grasp what intervention is necessary or effective; and

Whereas more clinical research is needed for people over 50 living with or at risk for HIV, as it is imperative to gain a greater understanding about how treatments interact with aging bodies: Now, therefore, be it

Resolved, That it is the sense of the House of Representatives that the National Institutes of Health and the Centers for Disease Control and Prevention should expand and intensify programs of research and related activities regarding the population of older individuals living with or at risk for HIV.

Carl Schmid

Deputy Executive Director

The AIDS Institute

Washington DC

202/462-3042-office
202/669-8267-cell
202/328-0467-fax
cschmid@theaidsinstitute.org
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« Reply #39 on: February 28, 2010, 10:31:10 AM »
Prevalence of hypovitaminosis D among HIV+ patients enrolled in a large italian cohort - see attached full poster report, interesting study

 

Reported by Jules Levin, 17th CROI Feb 16-19 2010 SF

Marco Borderi, Fabio Vescini, Alessandro Cozzi-Lepri, Antonio Di Caro, Maria Carla Re, Antonella d’Arminio Monfortefor the Icona Foundation Study Group

From Jules: although vitamin D insufficiency prevalence might be similar to that seen in the general population, the concerns in HIV are several: patients have so many risk factors for bone loss and fractures that vitamin D deficieny adds to the risk; if ARTs contribute to bone loss that increases a patients’ risk. S vitamin D loss among HIV+ individuals takes on a unique concern.

 

“Vitamin D insufficiency was defined as 25(OH)-vitD <75 nmol/l,while values <30 nmol/l were considered as vitamin Ddeficiency….VitD insufficiency and deficiency were found in 804 (54%) and 98 (7%) of the tests, respectively.”

 

AUTHOR CONCLUSIONS

This is the first large observational study confirming a very high prevalence of hypovitaminosis D in HIV positive patients living in western countries. Traditional risk factors for vit D deficiency are confirmed also in this setting: age, BMI, nationality, seasonality. Moreover, both immunodepression and high HIV viral load are associated with hypovitaminosis D.

Regarding the association with exposure to cART, we found that previous use of NNRTI-including regimens were associated with higher risk of vitD deficiency than previous exposure to PI. The analysis of the longitudinal changes in vitD according to the type of regimen started was largely unpowered and therefore the results are inconclusive.

Our data also seems to confirm that, in HIV positive individuals, vitamin D insufficiency is predictive of the risk of subsequent development of a number of severe events such as cardiovascular, renal disease and diabetes.

Overall, these data should be carefully considered in the management of HIV positive patients. Due to both the high prevalence of hypovitaminosis D and the safety of cholecalciferol administration, vitamin D supplements might be taken into account in our therapeutic choices.
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« Reply #40 on: February 28, 2010, 10:32:04 AM »
Engineering Adult Stem Cells Against HIV
by David Prentice
February 26, 2010

UCLA scientists have shown that they can engineer adult blood stem cells so that they lack a molecule necessary for HIV infection. The CCR5 receptor is a protein molecule on the surface of cells that is bound by HIV when the virus infects certain immune cells, acting as a receptor for the virus. The scientists used “short hairpin RNA” to knock down the expression of the CCR5 molecule in the human adult stem cells, effectively preventing the protein from being produced. These cells could reconstitute the immune system in a mouse model, indicating that the function of the immune cells was not inhibited. But the human cells, now without the CCR5 protein receptor, resisted HIV infection. The study, published in the journal Blood, provides a potential method for controlling HIV infection in patients.

The study follows a previous report of successful adult stem cell treatment for leukemia that also appears to have controlled HIV infection in the patient. The doctors specifically used an adult stem cell donor whose cells lacked the CCR5 molecule.
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« Reply #41 on: February 28, 2010, 10:35:05 AM »
http://singularityhub.com/2010/02/26/stem-cell-transplant-defeats-hiv/

Stem Cell Transplant Defeats HIV? Patient Still HIV Free After 2 Years

Add one more name to the ever growing list of diseases that have been defeated by stem cell treatments: HIV. That’s right, according to a recent report in the New England Journal of Medicine, a stem cell transplant performed in Germany has unexpectedly removed all signs of HIV from a 42 year old American patient. The unnamed white male was treated two years ago for Leukemia with a dose of donor stem cells and his HIV RNA count has dropped to zero and remained there since. While the treatment was for Leukemia, Dr. Gero Hutter and colleagues at the Charite Universitatsmedizen in Berlin had selected the stem cell donor for his HIV resistant genes. While there are still many questions unanswered, this is the first such case of stem cells treating HIV that has been reported in a NEJM-caliber publication. Ladies and gentlemen, this is not a “cure” for HIV/AIDS, but it is certainly a remarkable and promising find. There’s more you need to know about the situation, so read on.
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« Reply #42 on: February 28, 2010, 10:37:40 AM »
Assessment of Vitamin D Levels Among HIV-infected Persons in the Study To Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) - see attached full poster report

 

Reported by Jules Levin 17th CROI Feb 16-19 2010 SF

Christian Dao (CDC) et al. Pragna Patel (CDC), Sherri Pals (CDC), Timothy Bush (CDC), Frank Rahme (Abbott-Northwestern Hospital, Minneapolis, MN), E Turner Overton (Wash U, St Louis School of Med), Erna Kojic (miriam Hosp, Rhode Island), Kathy Wood (Cerner Corp, Vienna, VA).



AUTHOR DISCUSSION


Efavirenz, like antiepileptic drugs, induces cytochrome p450 enzymes to accelerate turnover of 25(OH)D and 1,25(OH)2D to inactive compounds (calcitronic acid) leading to lower levels of 25(OH)D.


Ritonavir is a potent inhibitor of 1-alpha-hydroxylase activity to convert 25(OH)D to 1,25(OH)2D, leading to an accumulation of 25(O)D.


Renal insufficiency possibly caused by damage to the renal proximal tubule, where 25(OH)D is converted to 1,25(OH)2D, would lead to an accumulation of 25)OH)D


AUTHOR RECOMMENDATIONS


Given reported associations between low levels of 25(OH)D and an array of chronic conditions, which are prevalent among HIV-infected persons, screening for 25(OH)D insufficiency is warranted.


Although one study has shown increases in 25(OH)D with vitamin D supplementation, other larger studies are necessary to assess the impact of viramin D supplementation on risk reduction of chronic conditions, such as osteoporosis/osteopenia and cardiovascular disease, among HIV-infected adults.
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« Reply #43 on: February 28, 2010, 10:39:26 AM »
Chronic Inflammation in HIV:  CROI 2010

 

David H Shepp, MD

Associate Professor of Medicine, Hofstra University School of Medicine

Division of Infectious Diseases, North Shore University Hospital-Manhasset

 

Cardiovascular Disease (CVD). 



Pathogenesis research has firmly established a link between chronic inflammation and atherosclerotic CVD in the general population.  Untreated HIV infection causes a state of intense chronic inflammation, which accounts it least in part for the higher rates and younger age of onset of cardiovascular disease in HIV infected patients.  ART reduces immune activation caused by HIV and many of the markers of chronic inflammation linked to CVD also improve.  However, many studies have shown that levels of immune activation and inflammatory markers remain elevated in HIV-infected individuals when compared to the HIV-uninfected, even when ART has produced years of durable viral suppression.  This raises the specter of ongoing increased CVD risk even in successfully treated patients.   Strategies to further reduce immune activation to normal levels are not established and represent an important unmeet need in HIV treatment research. 
In a symposium on Wednesday afternoon, Dr Priscilla Hsue, a cardiologist and associate professor of medicine at the UCSF gave an excellent review of HIV, inflammation and cardiovascular disease.  She cited new research presented at this conference exploring the relationship between immune activation/inflammatory markers and markers of CVD risk, the pathogenesis of residual chronic inflammation in patients treated with ART and of potential interventions that might be used in conjunction with traditional ART to further reduce inflammation.
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Offline red_Dragon888

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« Reply #44 on: February 28, 2010, 10:40:25 AM »
Vitamin D Deficiency and Bacterial Vaginosis among HIV-infected and -uninfected Women in the United States

Reported by Jules Levin
17th CROI, Feb 16-19 2010 SF

Audrey French1,2, O Adeyemi1,2, D Agniel2, M Yin3, K Anastos4, and M Cohen1,2
1Rush Univ Med Ctr, Chicago, IL, US; 2CORE Ctr, Stroger Hosp of Cook County, Chicago, IL, US; 3Columbia Univ Med Ctr, New York, NY, US; and 4Montefiore Med Ctr, Bronx, NY, US

Background:  Bacterial vaginosis (BV), the most frequent cause of vaginitis, is associated with morbidities such as premature labor and increased susceptibility to HIV. Recently an association between vitamin D deficiency (VDD) and BV was identified in pregnant women. We sought to replicate this finding in the Women’s Interagency HIV Study (WIHS).

Method:  A cross-sectional study of women participating in the WIHS, a longitudinal study of women with and at risk for HIV. Women in this substudy were from Chicago or New York. BV was defined by the Amsel criteria. VDD was defined as 25 (OH) D ≤20 ng/mL and insufficiency as >20 and ≤30 ng/mL.

Results:  Among 609 women studied (6 of whom were pregnant), BV was found in 19% (table). VDD was found in 60% and insufficiency in 23.5%. VDD was associated with black race, 268 of 397 vs 59 of 92 for whites, OR 3.16 (95%CI, 2.06 to 4.89), but not with HIV status, CD4, or age. Vitamin D level strongly correlated with BV (r= –0.14, P <0.001) and there was a dose response relationship; BV was most likely in women with VDD (OR 3.55), then women with insufficient levels (OR 2.12) compared with sufficient vitamin D. In multivariate analysis black race, AOR 6.03, VDD, AOR 2.46, and number of sex partners, AOR 1.54, were independently associated with BV.

Conclusions:  In this study of 609 HIV-infected and -uninfected women, BV and VDD were common and significantly correlated. VDD may partially explain the relationship between black race and BV and may be a modifiable risk factor for the disorder. Further study is needed to determine whether repletion of vitamin D will decrease the occurrence of BV.
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« Reply #45 on: February 28, 2010, 10:41:31 AM »
High Prevalence of Severe Vitamin D Deficiency in cART Naïve and Successfully Treated Swiss HIV Patients - see attached full poster report

 

Reported by Jules Levin, 17th CROI Feb 16-19 2010 SF

N Muller1*, CA Fux2*, B Ledergerber1, L Elzi3, P Schmid4, T Dang5, L Magenta6, A Calmy7, A Vergopoulos8, H Bischoff-Ferrari9 and the Swiss HIV Cohort Study. 1 University Hospital Zürich; 2 University Clinic for Infectious Diseases and University of Berne; 3 University Hospital Basel; 4 Kantonsspital St Gallen; 5 Centre Universitaire Hospitalier Vaudois, Lausanne; 6 Ospedale Civico Lugano; 7 Geneva University Hospital; 8 Institute of Clinical Chemistry, University Hospital Zurich; 9 Centre on Aging and Mobility, University of Zurich; 10 Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich Switzerland. * contributed equally

 

CONCLUSIONs

- With 42-52% in spring and 14-18% in fall vitamin D deficiency was highly prevalent

- Black ethnicity was a significant risk factor for vitamin D deficiency

- NNRTI-use was associated with significantly lower 25(OH)D levels

- TDF-use correlated with higher serum 1,25(OH)2D and serum alkaline phosphatase levels

- we suggest systematic screening for vitamin D deficiency in all HIV-positive patients

 

BACKGROUND

Recent studies have increased the awareness of beneficial effects of vitamin D. Besides being essential for bone growth and preservation, antineoplastic and immunmodulatory effects have been described.

Considering the high prevalence of osteopenia (up to 60%) and osteoporosis (up to 15%) as well as the increasing number of neoplasias, adequate vitamin D levels seem particularly important in the HIV-population.

AIMS

To determine vitamin D levels in HIV-positive patients comparing measurements by season as well as before and after the initiation of cART. To look for predictors for vitamin D deficiency
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« Reply #46 on: March 01, 2010, 10:13:23 AM »
Valganciclovir Reduces CD8+ T Cell Activation among HIV-infected Patients with Suboptimal CD4+ T cell Recovery During Antiretroviral Therapy - see attached full poster report

 

Reported by Jules Levin, CROI 2010 SF

Peter Hunt1, Jeffrey Martin1, Elizabeth Sinclair1, Lorrie Epling1, Juli Teague1, Mark Jacobson1, Russell Tracy2, Lawrence Corey3, and Steven Deeks1. 1University of California, San Francisco; 2University of Vermont; 3University of Washington



from Jules: there is a paper at CROI finding in HCV coinfected inflammation and non-AIDS death rates in the SMART Study (I send out report on this earlier today) is higher so I think that any major coinfection increases activation can cause what was found in this study regarding CMV. I'm not convinced its unique to CMV. But for CMV-positive individuals valgancyclovir appears to be helpful in reducing activation, just like my guess is curing HCV with peg/rbv.




AUTHOR CONCLUSIONS/IMPLICATIONS


Valganciclovir durably suppresses CMV replication (in CMV-positive, HIV+ individuals) and CD8+ T cell activation in HIV-infected patients with poor CD4 recovery during ART.



This reduction in CD8 activation does not appear to be mediated by a direct effect on HIV replication, but appears to be the result of reductions in CMV (or other herpesvirus) replication.



Thus, CMV (and possibly other herpesviruses) appears to be a major determinant of CD8+ T cell activation during antiretroviral therapy.



Given the potential impact of inflammation and immune activation on clinical outcomes (see poster 306), and the potential role of CMV in cardiovascular disease, T cell senescence, and aging, strategies to reduce CMV replication in HIV-infected individuals are worth pursuing in larger trials.
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« Reply #47 on: March 01, 2010, 10:15:01 AM »
Impact of CD8+ T Cell Activation on CD4+ T Cell Recovery and Mortality in HIV-infected Ugandans Initiating Antiretroviral Therapy - see attached full poster report



 ****NATAP Major CROI Poster*****

Reported by Jules Levin, CROI 2010 Feb SF

 

Peter W. Hunt1, Jeffrey N. Martin1, Isaac Ssewanyana2, John Bennett,1 Nneka Emenyonu3,4, Annet Kembabazi3, Torsten Neilands1, David R. Bangsberg4, Huyen Cao5, and Steven G. Deeks1. 1University of California, San Francisco; 2Joint Clinical Research Center, Kampala, Uganda; 3Mbarara University of Science and Technology, Uganda; 4Harvard School of Medicine; 5CA Department of Health Services



AUTHOR CONCLUSIONS/Implications
HIV+ Ugandans have higher CD8 activation than HIV+ San Franciscans both before and during suppressive ART.

- Unclear if these differences are explained by host genetics, viral factors, or prevalent co-infections.

High pre-therapy CD8 activation predicts poor CD4 recovery during suppressive ART in HIV+ Ugandans.

- Immune activation is an important determinant of CD4 recovery even in resource- limited settings with prevalent co-infections.

Persistently high CD8 activation during ART-mediated viral suppression predicts earlier mortality, independent of CD4 count.

- To our knowledge, this is the first demonstration that CD8 activation predicts mortality in the setting of suppressive ART.

- Interventions to decrease immune activation in this setting should be explored.
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« Reply #48 on: March 01, 2010, 10:15:48 AM »
T cell Senescence and Proliferation Defects Persist in Treated HIV-infected Individuals Maintaining Viral Suppression and Are Associated with Poor CD4+ T Cell Recovery - see attached full poster report

****NATAP Major CROI Poster****



Reported by Jules Levin, 17th CROI Feb 16-18 2010 SF

Peter Hunt, Elizabeth Sinclair, Lorrie Epling, Juli Teague, Qi Xuan Tan, Jeffrey Martin, Paula Lum, and Steven Deeks, University of California, San Francisco





Author Conclusions / Implications



• Despite having abnormally high T cell “activation” and entry of T cells into cell cycle, HIV-infected individuals also have significant T cell proliferative defects, which fail to normalize during ART.



• These proliferative defects may be the result of decreased T cell responsiveness, failure of cells to complete cell cycle, or apoptosis of proliferating cells.



• CD4+ T cell proliferative defects may contribute to poor CD4+ T cell recovery during antiretroviral therapy, independent of the extent of T cell activation and the extent of naïve CD4+ T cell depletion.



• Persistent proliferative defects may also explain why many CD28-CD8+ T cells fail to terminally differentiate and express CD57 in the setting of HIV infection.



• Elucidating the mechanisms responsible for T cell proliferative defects (i.e., IDO induction, lymphoid fibrosis, IL-7 responsiveness, etc.) may help identify targets for interventions to improve CD4 recovery and immune function during ART.

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« Reply #49 on: March 08, 2010, 10:32:31 AM »
HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs - pdf of full article attached



Nature Medicine

Published online: 7 March 2010 | doi:10.1038/nm.2109




Christoph C Carter1,2,7, Adewunmi Onafuwa-Nuga3,7, Lucy A McNamara4,5, James Riddell IV3, Dale Bixby3, Michael R Savona3,6 & Kathleen L Collins1,2,3,4





Abstract




HIV causes a chronic infection characterized by depletion of CD4+ T lymphocytes and the development of opportunistic infections. Despite drugs that inhibit viral spread, HIV infection has been difficult to cure because of uncharacterized reservoirs of infected cells that are resistant to highly active antiretroviral therapy (HAART) and the immune response. Here we used CD34+ cells from infected people as well as in vitro studies of wild-type HIV to show infection and killing of CD34+ multipotent hematopoietic progenitor cells (HPCs). In some HPCs, we detected latent infection that stably persisted in cell culture until viral gene expression was activated by differentiation factors. A unique reporter HIV that directly detects latently infected cells in vitro confirmed the presence of distinct populations of active and latently infected HPCs. These findings have major implications for understanding HIV bone marrow pathology and the mechanisms by which HIV causes persistent infection.






Despite the host immune response and treatment with HAART, HIV causes a persistent infection. Viral persistence is due in part to latent HIV reservoirs in resting CD4+ T cells1 that do not express viral proteins but can be induced to active infection by a variety of stimuli. However, recent studies of viral genetics have revealed that additional reservoirs probably exist2.





HPCs have been considered as a possible reservoir, but it has been difficult to establish that these cells are infected by HIV3, 4, 5, 6 because they are difficult to maintain in culture, and indirect measurements of infection may be confounded by contamination with other cell types. Here we used flow cytometry and recently developed culture conditions7 that have allowed us to conclude that a proportion of HPCs become infected after exposure to HIV both in vivo and in vitro.



Results



HIV infects and is cytotoxic to HPCs




To assess the susceptibility of HPCs to HIV, we examined intracellular expression of the HIV capsid protein Gag in purified bone marrow CD34+ cells treated with an HIV molecular clone derived from peripheral blood (89.6)8. 89.6 is a dual tropic virus that can use either CCR5 or CXCR4 as a co-receptor to enter cells. In this case, we used an envelope-deleted molecular clone (89.6ΔE) complemented with 89.6 envelope (89.6ΔEenv89.6) (Fig. 1). Three days after infection, 6% of CD34+ HPCs expressed intracellular HIV Gag (Fig. 2a). Antiretroviral treatment blocked Gag expression (Fig. 2a), and experiments with five other HIVs yielded similar results (Supplementary Fig. 1a). As previously reported for HIV-infected T cells9, 10, infected CD34+ cells downmodulated major histocompatibility complex class I (Fig. 2b).



HPCs are a heterogeneous collection of cells that include multipotent HPCs and stem cells (HSCs). Multipotent HPCs have a Lin−CD34+CD133+CD38− surface phenotype, where 'Lin' represents markers of specific hematopoietic lineages. After treatment with wild-type HIV 89.6 (Fig. 1b), both Lin+ and Lin− cells expressed intracellular Gag (Fig. 2c).




A time-course analysis revealed that Gag+ cells were lost rapidly in culture (Fig. 2d and Supplementary Fig. 1b). Moreover, infected cells showed high annexin V reactivity (Fig. 2e), and a high fraction of Gag+ cells had light scatter properties of dead cells (Supplementary Fig. 1c). Cell death required active viral gene expression, as transduction of the cells with a reporter virus (Fig. 1c) pseudotyped with an HIV envelope did not result in cell loss unless the HIV long terminal repeat (LTR) actively expressed HIV genes (Supplementary Fig. 1d).



Multipotent HPCs are susceptible to HIV infection




To assess the developmental capacity of infected HPCs, we used a minimal HIV genome (HIV-7SF-GFP, Fig. 1d) pseudotyped with 89.6 Env, which 'tagged' infected cells without causing cell death. We found that a proportion of CD34+ cells were infected (GFP+) (1–6% in replicate experiments (for example, Fig. 3a; initial sort purity shown in Supplementary Fig. 2a)), and a more primitive subset of these cells (CD34+CD38−CD133+) had a similar infection rate (Fig. 3b). Infection of CD133+ HPCs purified from bone marrow yielded similar results (Supplementary Fig. 2f,g). These infection rates were comparable to those of the fraction of CD34+ cells expressing both HIV co-receptors (Supplementary Fig. 3a,b).



CD133+ HPCs from umbilical cord blood (UCB) infected with HIV-7SF-GFPenv89.6 generated GFP+ colonies of erythroid (CFU-E), myeloid (CFU-M and CFU-GM) and multilineage (CFU-GEMM) origin, indicating that HIV can infect multipotent HPCs (Fig. 3c). Quantification revealed similar numbers of total colonies from uninfected and infected cells (Fig. 3d). We obtained similar results with a full-length HIV reporter (89.6-SIΔE-SF-GFP, Fig. 1e) that did not express HIV genes because of an LTR mutation (Fig. 3e,f).



Induction of latent HIV from infected HPCs




To assess latent infection, we asked whether induction of differentiation with phorbol 2-myristate 13-acetate (PMA) induced viral gene expression. In these experiments, we used bone marrow–derived HPCs (99.5% CD34+, Supplementary Fig. 2b) infected with a replication-defective HIV (HXB-ePLAP (Fig. 1f)) pseudotyped with the VSV-G envelope (HIV HXB-ePLAPenvVSV−G). This virus expresses a marker protein, placental alkaline phosphatase (PLAP). We found that PMA treatment increased the number of cells expressing PLAP 12-fold (Fig. 4a) and resulted in more viral particle production (Supplementary Fig. 4a) than treatment of cells with DMSO alone. Bone marrow immunodepleted for CD34+ cells was not viable under these conditions (Supplementary Fig. 4b).



We found similar numbers of integrated genomes in the presence or absence of PMA (Fig. 4b), indicating that PMA-induced gene expression was not due to effects on integration. Consistent with these results, the integrase inhibitor raltegravir blocked initial infection but not PMA-induced gene expression (Supplementary Fig. 5). We obtained similar results when the replication-defective PLAP-expressing HIV was pseudotyped with a bona fide HIV envelope (HXB-ePLAPenv89.6), albeit with lower infection rates (Fig. 4c).




We infected purified bone marrow–derived HPCs (98% CD34+, Supplementary Fig. 2d) with wild-type HIV 89.6 (Fig. 1b) and cultured them with or without granulocyte-macrophage colony–stimulating factor (GM-CSF) and tumor necrosis factor-α (TNF-α) to induce myeloid differentiation11. Treatment of infected HPCs with GM-CSF and TNF-α resulted in rapid release of HIV into the culture supernatant (Fig. 4d). In contrast, bone marrow mononuclear cells (BMMCs) immunodepleted for CD34+ cells did not release HIV (Fig. 4d) and rapidly died (Supplementary Fig. 4b–d,f). Flow cytometric analysis of the cells confirmed that treatment with GM-CSF and TNF-α stimulated intracellular HIV Gag expression (Fig. 4e) and that cells cultured with GM-CSF and TNF-α acquired myeloid markers (CD83) (Fig. 4f).




To assess the stability of latent HIV in HPCs, we infected CD34+ bone marrow–derived HPCs (99% pure, Supplementary Fig. 2e) with wild-type HIV 89.6. After 7 d, when the culture was uniformly Gag negative, we added GM-CSF and TNF-α to half of the cells. Addition of GM-CSF and TNF-α resulted in a resurgence of HIV gene expression compared with the untreated culture (Fig. 4g,h). We obtained similar results with a wild-type virus that uses only CXCR4, although, as expected, there was less viral spread in the differentiated myeloid cells (Supplementary Fig. 6b). The spread of infection in the culture was inhibited by treatment with the antiretroviral drug raltegravir, and supernatant from infected cells could be used to infect T cell lines (Supplementary Fig. 6).



Direct detection of latency




To detect latent infection in situ without inducing changes in the infected cells, we developed a new latency reporter virus (HIV 89.6-ΔE-SF-GFP (Fig. 1c)) that expresses GFP independently of the HIV LTR. Infection of T cells with HIV 89.6-ΔE-SF-GFPenv89.6 yields some cells expressing Gag and others expressing only GFP (Fig. 5a). Confirming that GFP+Gag− cells were latently infected, we found that CD4 downmodulation, which occurs only when HIV Nef, Vpu or Env is expressed12, occurred in Gag+ but not GFP+Gag− cells (Fig. 5a). In contrast, when we infected cells with a virus that expresses GFP from the HIV LTR (89.6-ΔE–IRES-GFP, Fig. 1g), the GFP-expressing cells downmodulated CD4 (Fig. 5a). We obtained similar results with peripheral blood mononuclear cells infected with 89.6ΔE-SF-GFPenv89.6 (Fig. 5b). Moreover, PMA and ionomycin treatment of Jurkat cells infected with the reporter virus increased Gag+ cell frequency and lowered GFP+Gag− cell frequency (Fig. 5c).



We observed separate populations of Gag+ and GFP+ cells in UCB-derived CD34+ HPCs infected with the latency reporter virus, indicating that active and latent infection occurred in this cell type (Fig. 5d). In culture, the Gag+ cells were rapidly lost, whereas the GFP+Gag− \cells persisted for at least 20 d (Fig. 5e and Supplementary Fig. 1d). Analysis of these cells revealed that many had a cell surface phenotype consistent with primitive HPCs (CD34+Lin− or CD34+CD38−) (Fig. 5f).



Evidence that CD34+ bone marrow cells are infected in vivo




We obtained samples from HIV-infected people with high viral loads (donors 1–6, Supplementary Table 1) and found that we could detect Gag+CD34+ cells in three of six freshly isolated samples (Fig. 6a and Supplementary Table 1). When we cultured the cells in GM-CSF and TNF-α, we could detect Gag expression in samples from all six donors (Fig. 6b,c). In contrast, donor BMMCs specifically depleted of CD34+ cells did not express Gag after culturing (Fig. 6c,d). The addition of the anti-HIV drug raltegravir, which inhibits new in vitro infection in T cells (Supplementary Fig. 7), partially suppressed the induction of Gag expression (Fig. 6c,d), confirming that a component of the infection we observed was the result of viral spread. We obtained similar results from a donor (number seven) who had undetectable viral loads for 2 years (Fig. 6e and Supplementary Table1).



Using a real-time PCR assay for integrated HIV DNA, we detected viral genomes in freshly isolated CD34+ cells from four of nine donors on HAART with undetectable viral loads for longer than 6 months (44%) (Fig. 6f,g). In these donors, we detected 40 (donor 7), 3.1 (donor 12), 39 (donor 14) and 2.5 (donor 15) HIV genomes per 10,000 CD34+ cells. We detected HIV genomes in BMMCs immunodepleted of CD34+ cells only for donor 12, for whom we detected1.2 HIV genomes per 10,000 CD34− cells. The limit of detection for this assay varied by donor but was approximately 1 genome per 10,000 cells, owing to the limited number of CD34+ cells obtained from each donor. Thus, it is likely that the proportion of donors in which we detected HIV genomes underestimates the percentage of HIV+, HAART-treated individuals harboring integrated HIV genomes in CD34+ cells.



Discussion




Long-lived cellular reservoirs of latent HIV genomes are a major obstacle to viral eradication. Here we demonstrate that HIV can infect hematopoietic progenitor cells in vivo and in vitro to cause an active, cytotoxic infection as well as a latent infection that can be induced to active infection by cytokine treatment.




Our finding that HIV infects HPCs with an immature phenotype has clear ramifications for HIV disease, because some of these cells may be long lived and could carry latent HIV for extended periods of time. Although further studies are needed to show that CD34+ stem cells are infected, our detection of HIV genomes in HPCs isolated from people effectively treated with HAART for more than 6 months confirms that HIV targets some long-lived HPCs. One might expect these results to predict the presence of identifiable proviral records in differentiated lineages that are known not to be susceptible. However, we show that actively infected HPCs are rapidly killed. Therefore, we expect latently infected HPCs will be killed by viral activation shortly after differentiation is induced.




Further studies are now needed to show that residual circulating virus in individuals on HAART is derived in part from HPCs, as previously demonstrated for resting memory T cells2. Additionally, studies examining the factors influencing HIV infection and latency in CD34+ cells, as well as limiting-dilution experiments to determine the fraction of proviral genomes in these cells that can be reactivated, would further understanding of this viral reservoir.



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Offline red_Dragon888

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« Reply #50 on: March 08, 2010, 10:36:40 AM »
Researchers: AIDS virus can hide in bone marrow



Kathleen Collins, an Associate Professor of Internal Medicine at the University of Michigan, and the Lead Author of a Study published in the journal, Nature Medicine said, “We found there was evidence that HIV in fact, does infect the bone marrow progenitor cells or parent cells that are the source of all of the different blood lineages in the body and moreover that HIV can take on a latent form and so we were able to detect the presence of virus ending cells even after patients had been on therapy for years”.


WASHINGTON — The virus that causes AIDS can hide in the bone marrow, avoiding drugs and later awakening to cause illness, according to new research that could point the way toward better treatments for the disease.

Finding that hide-out is a first step, but years of research lie ahead.

Dr. Kathleen Collins of the University of Michigan and her colleagues report in this week's edition of the journal Nature Medicine that the HIV virus can infect long-lived bone marrow cells that eventually convert into blood cells.

The virus is dormant in the bone marrow cells, she said, but when those progenitor cells develop into blood cells, it can be reactivated and cause renewed infection. The virus kills the new blood cells and then moves on to infect other cells, said.

"If we're ever going to be able to find a way to get rid of the cells, the first step is to understand" where a latent infection can continue, Collins said.

In recent years, drugs have reduced AIDS deaths sharply, but patients need to keep taking the medicines for life or the infection comes back, she said. That's an indication that while the drugs battle the active virus, some of the disease remains hidden away to flare up once the therapy is stopped.

One hide-out was found earlier in blood cells called macrophages. Another pool was discovered in memory T-cells, and research began on attacking those.

But those couldn't account for all the HIV virus still circulating, Collins said, showing there were more locations to check out and leading her to study the blood cell progenitors.

Finding these sources of infection is important because eliminating them would allow AIDS patients to stop taking drugs after their infection was over. That's critical in countries where the treatment is hard to afford and deliver.

"I don't know how many people realize that although the drugs have reduced mortality we still have a long way to go," Collins said in a telephone interview. "That is mainly because we can't stop the drugs, people have to take it for a lifetime."

The research was funded by the National Institutes of Health, Burroughs Wellcome Foundation, University of Michigan, Rackham Predoctoral Fellowship, National Science Foundation and a Bernard Maas Fellowship.

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« Reply #51 on: March 08, 2010, 02:53:40 PM »
News: http://www.the-scientist.com/blog/display/57203/
Stem cells: home of HIV?Posted by Jef Akst
[Entry posted at 7th March 2010 06:00 PM GMT]
Comment on this news story   
 
Human immunodeficiency virus (HIV) can infect bone marrow cells -- including, possibly, hematopoietic stem cells, according to a study published online today (March 7) in Nature.

 
Human Immunodeficiency Virus
Image: Wikimedia commons,
NIAID
The findings suggest the virus can hide in an inactive state for long periods of time, evading treatment, even in individuals without detectable viral loads.

"It's a little bit surprising to see that [HIV infects] progenitor cells, and [possibly] stem cells as well," said virologist Michael Bukrinsky of The George Washington University in Washington, DC, who was not involved in the research. It's a "novel and important" discovery that "will have big implications for pathogenesis of the disease and potential treatment of these patients."

Even patients who respond to highly active antiretroviral therapy (HAART) can harbor undetectably low viral loads, which can be reactivated later in life to cause a resurgence of the disease. Resting T cells can conceal such latent infections, and are the only well established and characterized HIV reservoirs. But a recent study found circulating viral genomes that differ from those found in T cells, suggesting that additional reservoirs may also exist.

When virologist Kathleen Collins of the University of Michigan in Ann Arbor and her colleagues exposed hematopoietic progenitor cells (HPCs) from bone marrow to HIV, some of the cells were quickly infected and killed by the virus. The team then pushed the progenitors to differentiate -- mostly into an antigen-presenting type of white blood cell -- and saw "a dramatic increase in viral gene expression," Collins said. These results suggested that HPCs likely harbored a latent form of the virus that could be activated by cellular differentiation. In short, HPCs represented another HIV reservoir.

"To my knowledge, we are the first to find another real reservoir beyond the resting T cell," Collins said.

"It reveals another obstacle" for viral eradication, said virologist Mario Stevenson of the University of Massachusetts Medical School, who did not participate in the study. "It shows us another area that we have to target in order to achieve a cure."

The researchers further confirmed the ability of HPCs to carry a latent infection by identifying HIV in the bone marrow in about 40 percent of patients who had undetectable viral loads for at least 6 months.

In order for cells to be able to maintain the latent virus for long periods of time, Collins said, they must live long enough to survive years of HAART. The discovery of latent infection in HPCs is "suggestive" that the new reservoir may be hematopoietic stem cells, which "we carry for our entire lives," she said. Furthermore, as stem cells have the capacity to self renew, the virus could spread through cell division, Collins added.

However, because of the type of HIV that persisted in HPCs, "I have my doubts of the functionality of these cells as reservoirs," Bukrinsky said. The HPCs infected by HIV predominately expressed chemokine receptor CXCR4, meaning they could only be infected by viruses that bind specifically to that receptor. These forms of the virus generally appear much later in infection than the major CCR5-binding viruses, which are primarily involved in transmission from one person to another, meaning the HPC reservoirs would not likely contribute to the spread of the virus through the population.

On the other hand, he added, because "CXCR4 viruses are more pathogenic than CCR5 [viruses], and HPCs are rapidly killed by the [activated] virus, patients will have some problems, even on HAART treatment, generating new T cells and macrophages."

"It all depends on the numbers," Bukrinsky said -- specifically, "the real percentage of these cells" that maintain a latent infection. With only nine patients in this study, it is unclear how frequently these cells harbor the infection. "This needs to be expanded to a bigger population to generate information about the importance of these reservoirs."

Furthermore, there may be additional reservoirs not yet identified, Stevenson said. "I think this study is going to generate a lot of interest," he said. "Whether it's the end of the story, I very much doubt it." 


Read more: Stem cells: home of HIV? - The Scientist - Magazine of the Life Sciences http://www.the-scientist.com/blog/display/57203/#ixzz0hcKRufh4
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« Reply #52 on: March 15, 2010, 10:53:02 AM »
HIV-Infected Postmenopausal Women at High Risk for Bone Fractures - pdf publication attached- (01/11/09)
JCEM
Conclusion: The lower BMD, higher prevalence of l ow BMD, and higher levels of bone turnover markers detected in HIV+ postmenopausal minority women could place them at high risk for future fractures.


"HIV infection was independently associated with lower bone mineral density after adjusting for body mass index (BMI) and traditional osteoporosis risk factors," said Yin. "While the reason for HIV-associated bone loss remains unclear, it may be related to increased levels of cytokines (proteins produced by cells that aid communication between cells), direct effects of antiretrovirals on bone cells or hormonal/nutritional de ficiencies that are common in HIV."
 
"Estrogen protects against the effect of cytokines on bone resorption," said Yin. "Therefore, as HIV-positive women become estrogen deficient during menopause, they may be at higher risk for accelerated bone loss and fracture."
 

--------------------------------------------------------------------------------
"In conclusion, low BMD was more common in postmenopausal HIV+ than HIV- minority women. HIV infection was independently associated with lower BMD after adjusting for BMI and traditional osteoporosis risk factors. BTMs (bone turnover markers) and TNFa were higher in HIV+ ART+ women, and multivariate modeling suggested that they may mediate the effect of HIV on BMD. Completion of the ongoing longitudinal study should permit assessment of whether increased bone turnover associated with ART translates into accelerated bone loss and increased fracture rates in aging postmenopausal women."
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« Reply #53 on: March 16, 2010, 02:16:45 AM »
http://www.boston.com/business/healthcare/articles/2010/03/15/genetix_raises_35m_for_gene_therapy_work/

Genetix gets $35m infusion for gene therapy work

From Xconomy.Com / March 15, 2010
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Sending your articleYour article has been sent. E-mail| Print| Reprints| Yahoo! Buzz| ShareThisText size – + Venture capitalists are giving the risky field of gene therapy a new dose of confidence — and cash. Genetix Pharmaceuticals, a 17-year-old developer of gene therapies, has replenished its coffers with a $35 million Series B round of venture capital.

The Cambridge-based company attracted the fresh capital after a study in France showed that one of the firm’s gene therapies blocked the progression of a debilitating brain disorder called adrenoleukodystrophy, or ALD, in two children. This is the disease that was featured in the acclaimed 1992 film “Lorenzo’s Oil,’’ the true story of a husband and wife who searched for a cure for their son with the crippling illness. While much testing will be required to bring the gene therapy to market, Boston’s Third Rock Ventures and Cambridge-based biotech giant Genzyme were convinced that there was enough promise in the data to make big bets on the company.

Third Rock and Genzyme Ventures, the venture unit of Genzyme, are the new investors in Genetix’s second-round financing, according to the company. The round includes investments from the firm’s previous VC backers Easton Capital, Forbion Capital Partners, and TVM Capital. The new funding came with major management changes at Genetix: Third Rock partner Nick Leschly is leading the firm as interim president; Phil Reilly, a venture partner at Third Rock, has become chief medical officer; and Mitchell Finer, a veteran biotech executive, is the new chief scientist. Genetix’s chief executive, Alfred Slanetz, is leaving the firm.

Gene therapies, which typically use viruses to deliver healthy genes into cells to treat diseases, have never been approved for the market nor lived up to the hype they initially generated about two decades ago. Genetix is one example of renewed faith in the science in some scientific and investor circles. The company, one of hundreds like it that formed in the 1990s to develop gene therapies, was recapitalized in 2004 and licensed technology from the French National Institute for Health and Medical Research. The French scientists who developed that technology have generated headlines around the world for its use to cure ALD in two high-profile cases.

“We’re at that same point that we were with monoclonal antibodies 12 to 15 years ago,’’ Finer, Genetix’s new chief scientific officer, says. “You look and see the resurgence of gene therapy data. We are poised to capitalize on those advancements.’’

Genetix, which has now closed $75 million in funding since its inception, adds its own twist to gene therapy. Rather than injecting its therapies directly into patients, the company treats patients’ own bone marrow after it has been extracted from them. Once the firm’s treatments have corrected the genes in patients’ bone marrow stem cells, the cells are infused back into the patients to cure their illness. To deliver healthy genes to cells, the company uses viruses derived from deactivated HIV that are designed to die off after their job is done.

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Offline red_Dragon888

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« Reply #54 on: March 16, 2010, 02:21:12 AM »
http://www.zacks.com/stock/news/31655/Optimistic+on+Cytori+Therapeutics

Analyst Blog   Optimistic on Cytori TherapeuticsBy: Jason Napodano, CFA

March 15, 2010 | Comments: 0
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CYTX Print    Share Last week, Cytori Therapeutics (CYTX - Analyst Report) was notified by the U.S. FDA that they will be required to conduct a clinical program prior to final approval of its Celution System. This was in-line with our expectations. Management plans to meet with the FDA in the next few months to discuss the requirements necessary for the Pre-Market Approval (PMA) program.

Assuming the meeting takes place this second quarter, Cytori should be in position to file the investigation device exemption (IDE) and initiate the program by the end of the year. Our best guess is that the FDA will require Cytori to conduct a 12-month study in approximately 100 patients looking at endpoints similar to the RESTORE-2 program conducted in Europe, including graft retention, patient and physician satisfaction and safety. If all goes smoothly, data should be available during the first half of 2012.

The filing could take place mid-2012. Therefore, we could be looking at a U.S. launch of the Celution System in 2013, with an indication for soft tissue filling and aesthetic body contouring in cosmetic and reconstructive surgery.

In the meantime, Cytori plans to ramp sales of its PureGraft product in the U.S. as a gateway product into the plastic surgery market. PureGraft is a low entry price, but high margin, useful tool that helps drive awareness and Cytori’s presence as a major player in aesthetic body contouring. The product compliments the Celase (Cytori’s proprietary enzyme product) and Celbursh (Cytori’s graft delivery instrument) products available for cosmetic and reconstructive procedures.

Ex-U.S. Market Key

The cosmetic surgery market outside the U.S. remains the key driver of revenues given the lack of reimbursement issues and growing movement toward the use of fat tissue procedures. We note that a direct sales model is the best strategy to target physicians and customers in the area of aesthetic body contouring, so management has become more active in the marketing and distribution of Celution around Europe and Asia.

Support for fat grafting procedures using Cytori’s Celution System has been growing nicely since the release of the interim data from the RESTORE-2 program in San Antonio in December 2009. Data at the San Antonio Breast Cancer Symposium, along with recent data at the Miami Breast Cancer Symposium in March 2010, demonstrated high patient and physician satisfaction, along with objective endpoints in both breast defect and overall breast shape post reconstruction.

In the above investigator-initiated studies for reconstruction, cell-enriched fat grafting with Cytori’s Celution System was safe and generally improved breast deformities and quality of life. Plus, the technique can be used alone or with other forms of breast reconstruction, including in reconstruction with implants.

We think these results bode very well for the future of cell-enriched breast reconstruction and Cytori’s Celution CRS System. We expect this to ramp significantly in the next few quarters as awareness, familiarity and reimbursement improve.

Expanding Cytori's Use?

Beside the progress being made in cosmetic and reconstructive surgery, Cytori is looking to expand the development of new applications for Celution System. In 2009, enrollment was completed in two cardiovascular disease trials, both of which met key end-points of safety and feasibility. The APOLLO trial (n=14) treated patients with acute myocardial infarction or heart attack. The PRECISE trial (n=27) included patients suffering from chronic myocardial ischemia.

Importantly, the trials demonstrated that physicians were able to safely extract a meaningful volume of adipose tissue, separate and concentrate the stem and regenerative cells using the Celution System and deliver these cells into the heart during the same interventional procedure.

Management noted that investigators in APOLLO saw an average 45% reduction in perfusion defect size at six month in the first five of the 13 patients testing, and although the data is still blinded, and 4 of the 13 patients are on placebo, this significant reduction in defect size is clearly far beyond what should normally be expected in this post-major heart attack population.

Our guess is that a pivotal program in approximately 250 patients will be necessary for a marketing claim with Celution for use in an acute MI population. This could begin in 2011. Outcomes from both of these studies will be reported on May 7, 2010 at the Seventh International Symposium on Stem Cell Therapy and Cardiovascular Innovations in Madrid, Spain. Additional studies are planned or underway including peripheral vascular disease, heart failure, liver insufficiency, kidney ischemia, burn scar adhesions, HIV facial wasting, wrinkle therapy, GvHD, and others.
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« Reply #55 on: March 16, 2010, 06:18:34 AM »

Red,

This looks promising for those with wasting from lipoatrophy.

v

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« Reply #56 on: March 16, 2010, 03:54:49 PM »
A miracle salve or another stem cell fraud?

‘Stem cell cosmetics’ don’t actually contain any human stem cells. Still, the potential but unproven benefits, many doctors say, don’t outweigh the risks.
March 17, 2010
 
 
In Korea, the term “stem cell” conjures up unhappy memories of Dr. Hwang Woo-suk, the cloning scientist who was crowned as a national hero back in 2004 only to be disgraced when it was revealed that much of his work had been fraudulent.

Yet even that national trauma didn’t damage the reputation of those two magic words, which now are being used to sell cosmetics. Makeup and skin products using stem cell-derived ingredients are already on the market, in fact.

Korean authorities have long harbored doubts about the safety of these products - but they haven’t decided just what to do about it yet.

In March last year, the Korea Food and Drug Administration was ready to propose a prohibition on the use of any material originating from human stem cells in cosmetics. The list of materials to be banned included stem cell culture fluid, as the agency said materials extracted from human cells could spread HIV or hepatitis viruses.

The measure would have removed from store shelves all cosmetics made from stem cells. Although stem-cell culture fluid is in the “International Cosmetic Ingredient Dictionary and Handbook,” which lists labeling names for the United States, the European Union and other countries, the KFDA was certain the fluid had safety issues.

In November, however, the agency softened its stringent stance, removing culture fluid from the banned list along with new regulations on cosmetics ingredients. Industry insiders said the government’s reversal came after harsh protests from cosmetics developers and manufacturers, who consider the ingredients a “new growth engine.”

Yet it wasn’t a blank check. The KFDA told cosmetics firms and consumers it would develop new regulations for stem cell cosmetics by June 2010. “Rather than entirely prohibiting [stem cell-related cosmetics], laying out safety rules seems like a better idea, given the attention [they attract] in the cosmetics communities at home and abroad,” read a KFDA statement released at the time.

That deadline won’t be met. A high-ranking official with the KFDA, part of the Health Ministry, said regulators are now “trying our best to make it by the year’s end.”

The official, who asked not to be named, said, “We don’t know for sure what’s in the stem cell culture fluid, and the culturing process leaves room for viral infection. It’s impossible that there are no problems with the material.”

Asked why the regulations are being delayed, the official only said, “We are now working on measuring sticks to guarantee [the cosmetics’] safety. It takes a sizable amount of time to review the technical feasibility of these measuring sticks.”

Despite Hwang’s fall from grace, products with the words “stem cell” on them still enjoy a halo effect on the Korean market, and “stem cell cosmetics” has emerged as a buzz phrase in the local beauty industry, particularly in the past two years. Promising to help fight the aging process and even revive youthful skin, the controversial beauty products are quickly gaining traction in the world’s seventh-largest cosmetics market.

RNL Bio, a Seoul-based biotech firm, launched what they call the country’s first stem cell cosmetics early last year. The company, which gained fame in 2008 for cloning a pit bull terrier at the request of an American woman whose dog had died, named the product “Dr. Jucre,” short for “Juvenescence Creation with Cell Regeneration.” Consisting of serum, cream and a sheet mask, Dr. Jucre started making house calls in the United States last August, and an RNL spokeswoman, Kim Yoon, said the line will hit shelves at major department stores in Seoul in the coming weeks.

Other local biotech ventures such as Histostem, Prostemics and BioSpectrum have followed in RNL’s footsteps, marketing stem cell-derived products that range in price from 100,000 won ($88) to millions of won. A flurry of smaller, low-profile enterprises and private hospitals are also involved in the burgeoning business. But the industry remains a statistical blind spot - no private or government figures on the size of the market, the number of companies or the consumer demographics are currently available.

 
 
Despite the name, no “stem cell cosmetics” actually contain human cells. Using actual human stem cells in cosmetics has never been allowed in Korea due to the potential risk of infection. The same is true in the United States and the EU.

In the majority of cases, the new cosmetics are comprised of conventional anti-aging agents derived from marine and botanical products, along with stem cell culture fluid - liquid that has been used to culture stem cells but does not actually contain any human tissue.

Actual stem cells are quite potent. As the only human cell capable of differentiating into many different types - into part of the liver or kidney, say - they could help repair the body by repairing otherwise irreversible damage to internal organs caused by disease or injury.

Adult stem cells, as opposed to the variety derived from embryos, which is not used for cosmetics, are usually extracted from fat tissue removed in liposuction surgery at hospitals. Some cosmetics producers take them from human umbilical cords. The companies say they have patients sign release forms to use the cells.

But where stem cells themselves may have a seemingly miraculous medical potential, stem cell culture fluid is still unproven. The companies say that stem cells discharge “cell growth chemicals” as they grow in the culture fluid, which gives their products the ability to slow the aging process and improve elasticity. The firms claim the substances are innovative enough to replace even such well-established treatments as retinol, a type of vitamin A, and the exfoliating agent glycolic acid.

Most stem cell cosmetics manufacturers cite clinical tests of up to 25 weeks that they say prove their products are highly effective in reducing wrinkles and boosting skin moisture and elasticity. They also cite documentation guaranteeing no health risks, though the validity of all these claims are often unverifiable.

But some others provide little more than flowery words. One company’s Web page depicts stem cells extracted from human umbilical cord blood as “a noncontroversial source of stem cells derived from nature’s own river of eternal youth.” When asked about stem cell cosmetics over the phone, a worker at the company said, “Since it’s not a chemical product, there should hardly be any side effects. If you discover red spots and rashes after testing it on the back of your hand, stop using it.”

Medical experts are suspicious of both the health risks and effectiveness of these wonder products. “Whether it’s cosmetics or medicine, any clinical test period is supposed to be lengthy. It’s too early for stem cell cosmetics producers to say their products have no health risks after testing them for less than a year. Infection through topical application is highly possible, even if problems have yet to arise since these products have been out for only two years,” said Dr. Oh Il-hoan, a professor at the Catholic University of Korea’s medical school. For example, Oh said, one medicine used to treat degenerative arthritis underwent clinical testing for four years, and when problems arose in the fourth year the entire project was scrapped.

“I can see that the state health watchdog is in a very hard place. On one side, it needs to encourage stem cell businesses, but on the other side it has lingering doubts about their safety. [The KFDA] has no choice but to be politically affected by the commercial sector,” Oh added.

Perhaps even worse for such potentially risky materials, no stem cell cosmetic product has yet been officially recognized for its anti-aging function, according to the KFDA. Another KFDA official, who also requested anonymity, said, “None of the so-called stem cell cosmetics out on the market have scientifically proven to us their effectiveness.”

Dr. Oh mused, “I’m afraid consumers are paying extra costs for effects that don’t exist. Even if the products show visible effects in the short term, nobody can guarantee if they will cause side effects later.”

Lee Ju-hong, a spokesman with the nonprofit Green Consumers Network in Korea, pointed out a more fundamental issue. “Basically, the KFDA is saying it wants to give more autonomy to those stem cell cosmetics producers and punish them if any issue erupts later. That is what the United States is doing,” he said.

But under the Korean legal structure, which is based on European law and emphasizes preliminary regulation, the KFDA loses its chance to penalize companies heavily once their products go to market. Korean law does not allow harsh punitive measures for companies causing consumer damage like U.S. law does, according to Lee.

The network spokesman continued, “The most desirable scenario would be for the government and cosmetics producers to quickly join together and come up with guidelines on stem cells in cosmetics. The government should not repeat its practice of issuing a prescription after the patient’s death.”
 
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #57 on: March 16, 2010, 03:57:03 PM »
CROI: Inflammation/activation linked to diseases of organ systems (heart, kidney, liver) & death in USA and now reported as well in Africa - HIV accelerated aging will be bigger problem in undeveloped countries


"New data presented at CROI 2010 further confirm the importance of chronic inflammation in the pathogenesis of non-AIDS complications of HIV infection, even in those successfully treated with ART. Despite some intriguing hints into the pathogenesis and treatment of chronic inflammation provided at this conference, the cause remains unclear and is likely multifactorial."
Chronic Inflammation in HIV: CROI 2010 - written by David H Shepp, MD Associate Professor of Medicine, Hofstra University School of Medicine Division of Infectious Diseases, North Shore University Hospital-Manhasset - (03/03/10)

"In aggregate, these studies provide evidence that ongoing HIV replication is unlikely to explain chronic inflammation but leave the door open to a possible benefit from intensification therapy via reduced immune activation. the link between chronic inflammation and CVD has been more thoroughly investigated, chronic inflammation appears to have an association with disease in other organ systems with overall mortality in HIV-infected persons. CRP and fibrinogen levels at baseline were strongly correlated with subsequent mortality. Baseline levels of either marker in the highest tertile were associated with about a 2.6-fold increased risk of death. The effect of elevated CRP or fibrinogen on mortality was significant across all levels of CD4, from <200 to >500. An analysis of non-AIDS mortality data from the SMART study suggested co-infection with HCV or HBV creates and especially dangerous proinflammatory state that strongly predisposes to death in the absence of continuous ART. For patients in SMART with elevated HA plus an increased level of any of the 3 biomarkers, the adjusted hazard ratio for death increased 4.4-6.1-fold compared to those with normal levels of HA and the biomarker. Gupta et al.8 reported a small pilot study to define urinary markers of kidney inflammation in patients with HIV and proteinuria but without other known conditions predisposing to proteinuria. Compared to HIV+ but non-proteinuric controls, urinary levels of two inflammatory cytokines, MCP-1 and RANTES (assessed by cytokine/creatinine ratio) were elevated. Another hypothesized cause of chronic immune activation is persistent viral coinfection, VGCV treatment suppressed CMV infection and reduced CD8+ activation markers significantly when compared to placebo. Patients who initiated ART during acute or early HIV infection in the OPTIONS study were compared to patients in the SCOPE cohort who initiated in the chronic phase when CD4 was less than 350. Arterial stiffness associated with traditional CVD risk factors and after adjustment, with a nadir CD4 <350."

CROI:Inflammation and Mortality in HIV-infected Adults: Analysis of the FRAM Study Cohort(02/25/10)
elevated levels of CRP & fibrogen (inflammation markers) were independently associated with predicting 5-year mortality regardless of degree of immunosuppression.

CROI: Rapid Progression of Atherosclerosis at the Carotid Bifurcation Is Linked to Inflammation in HIV-infected Patients - "These data strongly suggest that inflammation contributes to the higher risk of atherosclerosis noted in HIV-infected persons." - (02/22/10)
Elite controllers, without ART or viremia, have more rapid IMT progression compared to controls




CROI:Inflammation Is Associated with Endothelial Dysfunction Among Individuals with Treated and Suppressed HIV Infection - (02/26/10)

improvements in TNF-alpha, sTNFr, IL-2, IL-6, IL-8, and IL-17 in the first 12 weeks predicted better 24- and 48-week CD4 and virologic outcomes. The ACTG team concluded that assignment to immediate versus deferred antiretroviral therapy did not affect CD4 or viral load response at week 24 or 48. But they proposed that inflammation in the first 12 weeks of treatment for opportunistic diseases and bacterial infection affects 24- and 48-week CD4 and viral load--regardless of treatment assignment.


CROI: T-cell Senescence and T-cell Activation Predict Carotid Atherosclerosis in HIV-infected Women - (02/22/10)


CROI:Early Antiretrovirals in People Diagnosed With AIDS May Quell Inflammation Faster -- (02/25/10)


CROI:Risk of Non-AIDS Death in HIV/HCV-Coinfected People in SMART - - (03/01/10)
The SMART investigators proposed that, among people coinfected with HIV and a hepatitis virus, "those with impaired liver function are particularly in a pro-inflammatory state associated with excess risk of death from causes other than AIDS--and interruption of ART further exacerbates this pro-inflammatory state."


Activation of CD8 T Cells Predicts Progression of HIV Infection in Women Coinfected with Hepatitis C Virus - (02/24/10)


CROI: Non-AIDS-defining Events among HAART-treated Adults in an Urban US vs an Urban Sub-Saharan African Setting: 'high non-AIDS events rate in Africa' - (03/09/10)


CROI: In vitro Effect of CCR5 Antagonists on Innate Immune System: Maraviroc Inhibits the Migration of Neutrophils, Macrophages and Dendritic Cells - (03/05/10)

 These findings suggest that MVC might have a potential role in the down-regulation of HIV-associated chronic inflammation by blocking the recirculation and trafficking of macrophages and DC.



CROI: Cell Studies Point to Antiinflammatory Activity of Maraviroc -- (02/25/10)


CROI: Plasma Levels of Soluble CD14 (activation marker) Predict Mortality in HIV Infection - (03/05/10)
we investigated the relationship of baseline biomarkers of microbial translocation with all-cause mortality. Among patients with HIV infection, greater monocyte responsiveness to LPS, exhibited by high sCD14 levels, is associated with all-cause mortality, but other biomarkers of microbial translocation are not related to all-cause mortality. Patients in the highest quartile of LPS bioactivity, with sCD14 levels >2.71x106 pg/mL, had an OR of death of 6.0 versus the lowest quartile with levels <2.01x106 pg/mL (see table).


CROI: Effect of the Intensification with a CCR5 Antagonist Maraviroc on the Decay of the HIV-1 Latent Reservoir and Residual Viremia - reduced activation - (03/04/10)
In this preliminary analysis, intensification with MVC seems to accelerate the decay of the HIV latent reservoir. Unexpectedly, an increase in RV measured by SCA and episomal 2-LTRs DNA detection has been observed. A decrease in the activation of CD4 and CD8 cells was observed at wk12 of intensification.


CROI:Correlation of Inflammatory Biomarkers with the Framingham Coronary Risk Score in Antiretroviral-naïve HIV-1 Infected Patients - (03/03/10)
Framingham coronary risk scores and biomarker concentrations correlated well in this ART-naïve, virologically suppressed ARIES study population.


CROI: Impact of CD8+ T Cell Activation on CD4+ T Cell Recovery and Mortality in HIV-infected Ugandans Initiating Antiretroviral Therapy - (03/01/10)


CROI: Valganciclovir Reduces CD8+ T Cell Activation among HIV-infected Patients with Suboptimal CD4+ T cell Recovery During Antiretroviral Therapy - (03/01/10)
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #58 on: March 16, 2010, 03:57:48 PM »
CDC Analysis Provides New Look at Disproportionate Impact of HIV and Syphilis Among U.S. Gay and Bisexual Men




CDC Press Release March 10 2010


A data analysis released today by the Centers for Disease Control and Prevention underscores the disproportionate impact of HIV and syphilis among gay and bisexual men in the United States.




The data, presented at CDC's 2010 National STD Prevention Conference, finds that the rate of new HIV diagnoses among men who have sex with men (MSM) is more than 44 times that of other men and more than 40 times that of women.




The range was 522-989 cases of new HIV diagnoses per 100,000 MSM vs. 12 per 100,000 other men and 13 per 100,000 women.




The rate of primary and secondary syphilis among MSM is more than 46 times that of other men and more than 71 times that of women, the analysis says. The range was 91-173 cases per 100,000 MSM vs. 2 per 100,000 other men and 1 per 100,000 women.




While CDC data have shown for several years that gay and bisexual men make up the majority of new HIV and new syphilis infections, CDC has estimated the rates of these diseases for the first time based on new estimates of the size of the U.S. population of MSM. Because disease rates account for differences in the size of populations being compared, rates provide a reliable method for assessing health disparities between populations.




"While the heavy toll of HIV and syphilis among gay and bisexual men has been long recognized, this analysis shows just how stark the health disparities are between this and other populations," said Kevin Fenton, M.D., director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. "It is clear that we will not be able to stop the U.S. HIV epidemic until every affected community, along with health officials nationwide, prioritize the needs of gay and bisexual men with HIV prevention efforts."




For the purposes of determining rates of disease for MSM, CDC researchers first estimated the size of the gay and bisexual male population in the United States – defined as the proportion of men who reported engaging in same-sex behavior within the past five years. Based on an analysis of nationally representative surveys, CDC estimated that MSM comprise 2.0 percent (range: 1.4-2.7 percent) of the overall U.S. population aged 13 and older, or 4 percent of the U.S. male population (range: 2.8-5.3 percent). Disease rates per 100,000 population were then calculated using 2007 surveillance data on HIV and primary/secondary syphilis diagnoses and U.S. Census data for the total U.S. population.




The new analysis is the first step in more fully assessing the impact of HIV among MSM and other populations significantly affected by the disease. CDC is developing more detailed estimates of infection rates among MSM by race and age, as well as among injection drug users. CDC is also in the early stages of planning for estimates among heterosexuals. Ultimately, these data can be used to better inform national and local approaches to HIV and STD prevention to ensure that efforts are reaching the populations in greatest need.




Research shows that a range of complex factors contribute to the high rates of HIV and syphilis among gay and bisexual men. These factors include high prevalence of HIV and other STDs among MSM, which increases the risk of disease exposure, and limited access to prevention services. Other factors are complacency about HIV risk, particularly among young gay and bisexual men; difficulty of consistently maintaining safe behaviors with every sexual encounter over the course of a lifetime; and lack of awareness of syphilis symptoms and how it can be transmitted (e.g., oral sex). Additionally, factors such as homophobia and stigma can prevent MSM from seeking prevention, testing, and treatment services.




Also, the risk of HIV transmission through receptive anal sex is much greater than the risk of transmission via other sexual activities, and some gay and bisexual men are relying on prevention strategies that may be less effective than consistent condom use.




"There is no single or simple solution for reducing HIV and syphilis rates among gay and bisexual men," said Fenton. "We need intensified prevention efforts that are as diverse as the gay community itself. Solutions for young gay and bisexual men are especially critical, so that HIV does not inadvertently become a rite of passage for each new generation of gay men."




Preventing HIV and STDs among gay and bisexual men is a top CDC priority. CDC provides funding to health departments and community-based organizations throughout the nation to implement proven behavior-change programs for MSM and will soon expand a successful HIV testing initiative to reach more gay and bisexual men. Additionally, CDC is implementing an updated National Syphilis Elimination Plan in cities where MSM have been hardest hit by the disease, and will release an updated HIV prevention strategic plan within the next year to support the President's upcoming National HIV/AIDS Strategy. CDC officials note that the new analysis released today underscores the importance of the HIV and STD prevention efforts targeting gay and bisexual men recently announced as part of the President's fiscal year 2011 budget proposal.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #59 on: March 16, 2010, 03:59:32 PM »
http://www.natap.org/2010/CROI/croi_35.htm

T-cell Senescence and T-cell Activation Predict Carotid Atherosclerosis in HIV-infected Women
 
 
 
  *******NATAP CROI POSTER OF THE YEAR 2010******
 
Reported by Jules Levin
CROI 2010 Feb 16-19 SF
 
Robert C Kaplan1, PhD, Elizabeth Sinclair2, PhD, Alan L Landay3, PhD, Nell Lurain3, PhD, Stephen J Gange4, PhD, Richey Sharrett4, MD, DrPH, Xiaonan Xue1, PhD, Peter Hunt2, MD, Howard N Hodis5, MD, Steven g Deeks,2, MD
 
Affiliations: 1Albert Einstein College of medicine, 2Univ of California-SF, 3Rush University Medical Center, 4Johns Hopkins Bloomberg School og Public Health, 5Univ of Southern California
 
Conclusions
 
Collectively, these observations are consistent with a model in which untreated HIV infection results in immune activation, accelerated immunologic aging and the emergence of a population of potentially dysfunctional immunosenescent T cells. Antiretroviral therapy-mediated suppression of HIV replication may only partially reverse or prevent this process. The presence of a large population of activated and/or senescent T cells may be causally associated with the premature onset of CVD.
 
SUMMARY OF RESULTS/DISCUSSION
 
Consistent with prior data, HIV infection was associated with markedly elevated levels of activated (CD38+HLA-DR+) peripheral T-cells. Viremic suppression through effective antiretroviral therapy appeared to reduce but not completely reverse this process.
 
Among HIV-infected women, T-cell activation was associated with markers of subclinical carotid artery disease after adjustment for multiple confounders. Among HIV-infected women, CD8+ T-cell senescence, and to a lesser extent CD4+ T-cell senescence (phenotypically defined by absence of CD28 and presence of CD57), were also associated with HIV disease and with the presence subclinical carotid artery disease.
 
These associations of T-cell activation and senescence with carotid artery parameters were not observed in a population of HIV-uninfected controls who were studied using identical methods and who had comparable cardiovascular risk factor profiles. Relatively small sample size of the HIV-uninfected group is a limitation.
 
ABSTRACT
 
HIV infection results in chronic elevated T cell activation and inflammation. This inflammatory state is reduced but not normalized by antiretrovirial therapy. Among treated patients, inflammatory markers are associated with risk of death and cardiovascular events. In HIV seronegative individuals, inflammation may be associated with accelerated immunologic aging (immunosenescence). The degree to which immunosenescence exists during treated HIV infection, and the impact of this process on cardiovascular disease has not been defined.
 
METHODS
 
HIV infected (n=115) and matched HIV uninfected (n=43) participants in the Women’s Interagency HIV Study underwent B-mode carotid ultrasound. Measurements included carotid artery distensibility and carotid intima-media thickness (IMT), with carotid lesions defined as IMT >1,5mm. T-cell activation (CD38+HLA-DR+) and T-cell senescence (CD57+CD28-) were measured using flow cytometry.
 
(from Jules: Carotid distensibility (CD) is a measure of carotid artery elasticity that has been introduced as a risk factor for cardiovascular disease. Morphological studies have indicated that arterial distensibility depends on different factors such as blood pressure and age. Aging is the main variable responsible for functional changes in the arterial wall leading to an increase in arterial stiffness)
.
 
RESULTS
 
The mean age of the HIV-infected and unifected women were 46.6 and 47.2 years, respectively. Most subjects were on HAART (n=66) and many had undetectable viral loads (n=28).
 
As compared to the HIV uninfected subjects, the treated women with undetectable viral loads had higher levels of CD4 T-cell activation (p<.01) and CD8 T-cell activation (p<.02); CD8+ T cell senescence (p=0.07) but not CD4+ T cell senescence (p=0.53) also tended to be increased in the treated aviremic women.
 
Carotid artery distensibility was decreased among the HIV-infected group (p=0.01). Among HIV-infected women, higher CD4+ activation (p<0.01) and CD8+ activation (p=0.02) were significantly associated with reduced carotid artery distensibility, independent of age, CD4 count, and viral load.
 
CD4+ senescence (p=0.01) and CD8+ senescence (P=0.01) were also associated with reduced carotid artery distensibility among HIV-infected women.
 
Similarly, carotid lesions were significantly increased among HIV-infected women with CD4+ T-cell count<200 as compared with controls, and among the HIV-infected subjects there was an association of T-cell activation and senescence with the presence of carotid lesions.
 
1. RATIONALE
 
R-cell CD38+ expression, a marker of immune activation, predicts early and late HIV disease course (Giorgi JID 1999).
 
Immune activation predicts HIV prognosis independent of viral load and may be one mechanism contributing to CD4+ T-cell loss during untreated HIV, or inability to reconstitute peripheral CD4+ T cells during treated HIV.
 
Activated T-cells are present in artherosclerotic plaque and may contribute to CVD (CD4+, possibly CD8+) (Hansson Am J Path 1989).
 
Aging is associated with emergence of senescent cells, typically defined as long-lived, apoptosis-resistant cells that have limited proliferative capacity and often have a secretory phenotype (Campisi Nature 2009). Senescence is stimulated by environmental stress, inflammation, and genetic instability (mutations, epigenetic changes).
 
Senescent R-cells (defined by the loss of CD28 and/or presence of CD57) may relate to HIV disease stage, inflammatory response, and CVD (Liuzzo JACC 2007).
 
Given the evidence that HIV infection may be associated with premature onset of age-related diseases, we investigated the effect of untreated and treated HIV on T-cell immunosenescence. We also investigated the impact of T-cell activation and senescence on subclinical carotid artery disease measured by B-mode ultrasound.
 
2. SUBJECTS
 
The study was conducted among participants in the Women’s Interagency HIV Study (WIHS), prospective multicenter study conducted at 6 US centers.
 
Characteristics of HIV-infected and HIV-uninfected women.


*over duration of study enrollment. For subjects who entered the study on HAART, peak plasma HIV RNA and nadir CD4 counts were also obtained by chart review.
 
3a. Results: T-cell activation and senescence in relation to HIV disease stage
 
Senescence
 



Activation
 





3b. Results: CD4+ and CD8+ T-cell activation in relation to subclinical carotid artery disease
 
Among HIV+ women, higher expression of activation markers on CD4+ (left panel) and CD8+ (right panel) T-cells was associated with carotid lesions.
 
Interaction terms suggested that higher T-cell activation was associated with carotid lesions in HIV+, but not in HIV- (p = 0.061 for CD4+, p = 0.023 for CD8+).


Among HIV-infected women, higher CD4+ (left panel) and CD8+ (right panel) senescence were associated with reduced carotid artery distensibility.


3c. Results: Multivariate analyses of T-cell activation and senescence in relation to subclinical carotid artery disease
 
Among HIV-infected women, associations between T-cell activation and senescence and subclinical carotid artery disease persisted after adjustment for HIV-related and CVD-related covariates.
 
Shown at left are models adjusted for age and use of classes of antiretroviral medications. Results were unaffected by further adjustment for CVD risk factors, VL, and socioeconomics.
 
Associations are shown as PR or ß per SD change in activation/senescence. cIMT, carotid intima-media thickness of the right common carotid artery


6. Detailed Methods
 
Carotid ultrasound: High resolution B-mode carotid artery ultrasound was used to image the far wall of the right common carotid artery (CCA), the internal carotid artery, and the carotid bifurcation according to the procedure of Hodis and colleagues. Right distal CCA intima-media thickness was measured (cIMT). The presence of carotid lesions was defined as a focal intima-media thickness >1.5 mm in any of the imaged segments. To estimate arterial distensibility we obtained right CCA diameters at systole (DS) and diastole (DD) and brachial artery pulse pressure (PP); lower distensibility values reflect a stiffer artery. Standardized carotid artery ultrasound images were centrally measured by automated computerized edge detection using an in-house developed software package (Prowin, Patent, 2005, 2006). Laboratory assays: HIV infection was determined via serologic testing using enzyme-linked immunosorbent assay (ELISA) and confirmed using Western blot assays. Plasma HIV viral load was quantified using nucleic acid sequence based amplification commercial assays with a lower limit of quantification of 80 copies/mL (bioMérieux, Boxtel, NC), and total peripheral CD4+ T-cell counts were measured with standard flow cytometric methods, at laboratories participating in the National Institutes of Health/National Institute of Allergy and Infectious Disease Flow Cytometry Quality Assessment Program. T-cell activation and senescence were measured by immunophenotyping performed at the UCSF Core Immunology Laboratory, using methods that have been optimized and validated for frozen peripheral blood mononuclear cells (PBMCs). Cryopreserved PBMCs were rapidly thawed in warm media, washed, stained with Viacount (Millipore, Billerica, MA) and run on a Guava PCA (Millipore) to determine cell number and viability. Samples with viability of less than 40% were not analyzed. The mean PBMC viability was 75.0% in HIV-infected and 77.5% in HIV-uninfected women. PBMCs were stained for Aqua Amine Reactive Dye (Invitrogen, Carlsbad, CA) to exclude non-viable cells, and for surface expression of CD3, CD28 (BD Pharmingen, San Diego CA), CD4, CD38, HLA-DR (BD Biosciences, San Jose, CA), CD8 (Invitrogen) and CD57 (Biolegend, San Diego, CA). Stained cells were run on a customized BD LSR II and data analyzed using Flow Jo (Tree Star, Ashland, OR) to quantitate CD4+ and CD8+ T-cells expressing activation (CD38, HLA-DR) and senescence (CD28-, CD57+) markers.
 
Funding: Funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632), and co-funded by the National Cancer Institute, the National Institute on Drug Abuse, the National Institute on Deafness and Other Communication Disorders, the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131), the National Heart, Lung and Blood Institute (1R01HL095140, 1R01HL083760 to Albert Einstein), NIH/NIAID funding to the UCSF-GIVI Center for AIDS Research (P30AI027763) and NCR funding to the UCSF Clinical and Translational Science Institute (UL1RR024131). 
 
 
 
 
 
 
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #60 on: March 16, 2010, 04:04:41 PM »
http://www.natap.org/2010/CROI/croi_88.htm

Activation of CD8 T Cells Predicts Progression of HIV Infection in Women Coinfected with Hepatitis C Virus
 
 
 
  The Journal of Infectious Diseases March 15 2010
 
from Jules: it appears HCV causes immune activation in addition to the activation caused by HIV leading to higher AIDS risk & HIV disease progression & death. HCV viral load in this study is associated with developing AIDS & death!
 
"HCV coinfection was associated with increased CD8 activation. Finally, our most important finding was the statistically significant association between the level of activated CD8 T cells and incident AIDS among HCV-positive viremic women. HCV-positive viremic women with >43% activated CD8 T cells had an almost 3-fold increased risk of AIDS-defining conditions and/or AIDS-related deaths compared with HCV-positive viremic women with <26% activated CD8 T cells. This was not found for HCV-negative women"........Ongoing antigen-driven activation of CD8 T cells ultimately leads to CD8 T cell exhaustion and replicative senescence, which lead to inability to fight opportunistic pathogens....... factors that drive immune activation may increase the available targets for further viral replication. Finally, HCV infection may impair T cell maturation more globally to a more immature primed activated phenotype and also may impair responses to Toll-like receptors, suggesting that both the innate and adaptive arms are affected [24, 39].....Animal studies have suggested that immune activation, rather than viral load, is linked to HIV disease progression [8].....The 592 women with immune activation data were slightly older (mean age, 37.4 vs 35.5 years); were more likely African American or Hispanic (82.5% vs 77.5%), injection drug users (53% vs 27%), and smokers (58% vs 49%); and had higher CD4 cell counts (mean, 439 vs 403 cells/µL) and CD8 cell counts (mean, 964 vs 867 cells/µL) than women without these data (data not shown)."
 
"...HCV-positive viremic women had a statistically significantly higher percentage of activated CD8 T cells (p<.001)...
 
...HCV-positive viremic women with HIV coinfection who have high levels of T cell activation may have increased risk of AIDS...
 
....In adjusted generalized estimating equation models, percentage of CD8+CD38+DR+ T cells was statistically significantly positively associated with HCV status (p=.04). Other independent correlates of CD8 activation included HIV RNA level and ART.......HCV-positive viremic women were more likely to have bacterial pneumonia (20% vs 13%; p=.002 ), dementia and/or encephalopathy (11% vs 7%; p=.02), and wasting syndrome (12% vs 8%; p=.03) than were HCV-negative women.....HCV-positive viremic women were more likely to develop AIDS with an HCV RNA level of >2.3 million IU/mL.....and were more likely to die an AIDS-related death with an HCV RNA level of >3.98 million IU/mL...
 
....Immune activation has been closely linked to HIV disease progression [1, 4, 5, 34-36], but to our knowledge this association has not previously been reported in the setting of HCV coinfection....
 
.....our findings from this large cohort study, which included 1307 women, are notable: HCV coinfection was associated with increased CD8 activation. Finally, our most important finding was the statistically significant association between the level of activated CD8 T cells and incident AIDS among HCV-positive viremic women. HCV-positive viremic women with >43% activated CD8 T cells had an almost 3-fold increased risk of AIDS-defining conditions and/or AIDS-related deaths compared with HCV-positive viremic women with <26% activated CD8 T cells. This was not found for HCV-negative women.....data suggest that the increased risk of HIV disease progression among HCV-coinfected women with high levels of CD8 activation may be due to immune dysfunction....
 
....We determined that (1) HCV viremia is associated with AIDS outcome, independent of injection drug use, HIV RNA level, CD4 cell count, and ART (Table 2); (2) HCV viremia is associated with CD4 and CD8 activation, independent of HIV RNA level (Table 3); and (3) high levels of CD8 activation are associated with AIDS in HCV-positive viremic women but not in HCV-negative women.....
 
.....In conclusion, our study demonstrates that HIV-coinfected HCV-positive viremic women are at increased risk for AIDS-defining conditions compared with HCV-negative women, possibly because of high levels of activation of T cells, especially CD8 T cells, which indicates increased immune dysregulation in this population of women. Lower levels of activation of both CD8 and CD4 T cells and activation of CD8 T cells expressing only HLA-DR is protective against AIDS. Further study is needed to understand better the pathogenesis of T cell activation, especially of CD8 T cells in relation to HIV disease. HCV-positive viremic women may benefit from treatment of HIV and HCV infection to prevent significant immunologic changes and improve long-term outcome. Assessing CD4 and CD8 T cell activation could help clinicians evaluate their patients' risk of developing AIDS

 
  
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #61 on: March 17, 2010, 01:15:55 PM »
Regulus Announces U.S. Allowance of Stanford Patent Application Covering miR-181a Function in Immune Cells
- miR-181a Patent Exclusively Licensed to Regulus Strengthens Regulus Patent Estate in Immuno-Inflammatory Diseases -


CARLSBAD, Calif., Mar 17, 2010 (BUSINESS WIRE) -- Regulus Therapeutics Inc. announced today that the United States Patent and Trademark Office (USPTO) has allowed claims in U.S. Application Serial No. 11/977,506 covering methods of antagonizing miR-181a to regulate immune response. This patent is owned by Stanford University and licensed exclusively to Regulus. miR-181a has been shown to regulate the response of immune cells, such as T lymphocytes, to specific stimuli and modulation of miR-181a could lead to a novel treatment of inflammatory disease.


"We are pleased with the decision of the USPTO to allow this first application based on the Li et al. patent filing. We are applying our expertise in microRNA biology and nucleic acid chemistry to develop novel medicines for treating inflammatory disease, and this new allowance will expand the scope of our exclusivity surrounding the anti-miR approach to miR-181a," said Garry E. Menzel, Ph.D., Executive Vice President of Corporate Development and Finance of Regulus Therapeutics. "More broadly, we continue to build a robust patent portfolio that supports our strategy of developing and commercializing high-impact microRNA-based therapeutics in multiple disease areas."


Data published in 2007 by scientists at Stanford University and Alnylam Pharmaceuticals in the journal Cell [li QJ et al. 2007 Apr. 6;129(1):147-61] demonstrated that modulation of miR-181a levels in an immune cell modified the sensitivity of the cell to specific stimuli. Increased expression of miR-181a led to an increase in immune cell response to an inflammatory stimulus. Conversely, decreasing levels of miR-181a in immune cells de-sensitized the cell to the stimulus. Consistent with this observation, using an anti-miR to antagonize miR-181a function reduced immune cell response to a stimulus.


The newly allowed claims cover methods of modulating miR-181a in T cells, to raise the T cell receptor signaling threshold, and decrease the sensitivity of T cells to antigen stimulation. The claims cover the use of a broad class of anti-miRs targeting miR-181a, including anti-miRs having varying lengths and chemical modifications.


About microRNAs
The discovery of microRNA in humans is one of the most exciting scientific breakthroughs in the last decade. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, that do not encode proteins but instead regulate gene expression. Nearly 700 microRNAs have been identified in the human genome, and more than one-third of all human genes are believed to be regulated by microRNAs. As a single microRNA can regulate entire networks of genes, these new molecules are considered the master regulators of the genome. microRNAs have been shown to play an integral role in numerous biological processes including the immune response, cell-cycle control, metabolism, viral replication, stem cell differentiation and human development. Many microRNAs are conserved across multiple species indicating the evolutionary importance of these molecules as modulators of critical biological pathways. Indeed, microRNA expression or function has been shown to be significantly altered in many disease states, including cancer, heart failure and viral infections. Targeting microRNAs opens the possibility of a novel class of therapeutics and a unique approach to treating disease by modulating entire biological pathways.


About Regulus Therapeutics Inc.
Regulus Therapeutics is a biopharmaceutical company leading the discovery and development of innovative new medicines based on microRNAs. Regulus is targeting microRNAs as a new class of therapeutics by working with a broad network of academic collaborators and leveraging oligonucleotide drug discovery and development expertise from its founding companies Alnylam Pharmaceuticals /quotes/comstock/15*!alny/quotes/nls/alny (ALNY 18.16, +0.01, +0.06%) and Isis Pharmaceuticals /quotes/comstock/15*!isis/quotes/nls/isis (ISIS 9.80, -0.07, -0.71%) . Regulus is advancing microRNA therapeutics towards the clinic in several areas including hepatitis C infection, cardiovascular disease, fibrosis, oncology, immuno-inflammatory diseases, and metabolic diseases. Regulus' intellectual property estate contains both the fundamental and core patents in the field as well as over 600 patents and more than 300 pending patent applications pertaining primarily to chemical modifications of oligonucleotides targeting microRNAs for therapeutic applications. In 2008, Regulus entered into a major alliance with GlaxoSmithKline to discover and develop microRNA therapeutics for immuno-inflammatory diseases. In 2010, Regulus entered into a new collaboration with GlaxoSmithKline to develop and commercialize microRNA therapeutics targeting microRNA-122 for the treatment of Hepatitis C Viral infection. For more information, visit www.regulusrx.com.


Forward-Looking Statements
This press release includes forward-looking statements regarding the future therapeutic and commercial potential of Isis', Alnylam's and Regulus' business plans, technologies and intellectual property related to microRNA therapeutics being discovered and developed by Regulus, including statements regarding the therapeutic potential of targeting miR-181a. Any statement describing Isis', Alnylam's or Regulus' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such products. Such parties' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause their results to differ materially from those expressed or implied by such forward-looking statements. Although these forward-looking statements reflect the good faith judgment of the management of each such party, these statements are based only on facts and factors currently known by Isis, Alnylam or Regulus, as the case may be. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Regulus', Alnylam's, and Isis' programs are described in additional detail in Alnylam's and Isis' annual reports on Form 10-K for the year ended December 31, 2009. Copies of these and other documents are available from Alnylam or Isis.
SOURCE: Regulus Therapeutics Inc.
Regulus Therapeutics
  Zachary Zimmerman, Ph.D., 760-268-6811
  or
  Media:
  Russo Partners
  Heidi Chokeir, Ph.D., 619-528-2217

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« Reply #62 on: March 18, 2010, 06:56:45 AM »
Gene-based stem cell therapy specifically removes cell receptor that attracts HIV
Science Centric | 17 March 2010 13:41 GMT
   
http://www.google.com/url?sa=X&q=http://www.sciencecentric.com/news/article.php%3Fq%3D10031772-gene-based-stem-cell-therapy-specifically-removes-cell-receptor-that-attracts-hiv&ct=ga&cad=7:2:0&cd=y1msiFn7Oa0&usg=AFQjCNFTIQb1OYAYxg1Nn0iWdRu8xKpJdA

Discovery of cellular 'switch' may provide new means of triggering cell death, treating disease — [16 Mar 2010] — A research team led by the University of Colorado at Boulder has discovered a previously unknown cellular 'switch' that may...


A new type of stem cells found in prostate may be involved in cancer — [9 Sep 2009] — A new type of stem cell found in the prostate of adult mice can be a source of prostate cancer, according to a new study...


Study reveals new genetic culprit in deadly skin cancer — [30 Aug 2009] — Drawing on the power of DNA sequencing, National Institutes of Health researchers have identified a new group of genetic...


New technique could eliminate inherited mitochondrial disease — [26 Aug 2009] — Researchers have developed an experimental technique with the potential to prevent a class of hereditary disorders passed...

More Health...
UCLA AIDS Institute researchers successfully removed CCR5 - a cell receptor to which HIV-1 binds for infection but which the human body does not need - from human cells. Individuals who naturally lack the CCR5 receptor have been found to be essentially resistant to HIV.

Using a humanised mouse model, the researchers transplanted a small RNA molecule known as short hairpin RNA (shRNA), which induced RNA interference into human blood stem cells to inhibit the expression of CCR5 in human immune cells.

The findings provide evidence that this strategy can be an effective way to treat HIV-infected individuals, by prompting long-term and stable reduction of CCR5.

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« Reply #63 on: March 19, 2010, 10:49:26 AM »
ViiV Healthcare Responds to Growing ADAP Patient Waiting Lists



ViiV Healthcare would like to inform people that the company has a patient assistance program that can assist many patients in accessing the HIV medicines of ViiV Healthcare while they are on waiting lists for AIDS Drug Assistance Programs (ADAPs). Patients who are accepted to ADAPs are uninsured, underserved, and often learn of their HIV diagnosis at a late stage of their disease. For patients who are diagnosed with late stage disease and recommended for treatment, timely access to medicines is critical, and delays can lead to the development of life-threatening opportunistic infections.



The current economy and rising HIV infection rates have resulted in growing waiting lists for state ADAPs. As a result, patients with an HIV or AIDS diagnosis are waiting for access to life-saving medicines that may also reduce medical costs associated with uncontrolled HIV disease. According to the National Alliance of State and Territorial AIDS Directors (NASTAD), as of March 5, 2010, there were 662 individuals on ADAP waiting lists in ten states.



ViiV Healthcare believes that access to healthcare among economically disadvantaged populations, both at home and abroad, is one of the world's most pressing social challenges. Along with the HIV community, state and local government, and others, we are committed to increasing access to care.



Through Bridges to Access, ViiV Healthcare offers assistance to patients with a monthly household income below 250 percent of the federal poverty level who do not have prescription drug benefits through any insurer, payer, or program. Patients on ADAP waiting lists are considered uninsured for purposes of determining eligibility for the patient assistance program. ViiV Healthcare expects that the majority of ADAP clients on waiting lists will have incomes that will allow them to qualify for help through Bridges to Access. Individuals can find out if they qualify by visiting www.bridgestoaccess.com or by contacting ViiV Healthcare at 877-844-8872.



ViiV Healthcare believes it is critical to inform people about access to HIV medicines through patient assistance programs like Bridges to Access. We will work alongside NASTAD and other groups to ensure patients, case workers, and others involved in assisting those on ADAP waiting lists are aware that our program is available. Information about the eligibility requirements for other patient assistance programs can be found by contacting the Partnership for Prescription Assistance at 1-877-477-2669 or by visiting www.PPARx.com.
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« Reply #64 on: March 19, 2010, 10:50:37 AM »
Insurer targeted HIV patients to drop coverage


* HIV positive at 17, college freshman lost insurance
* Fortis used algorithms to target HIV patients
* Fortis, now Assurant, ordered to pay $10 million
By Murray Waas
WASHINGTON, March 17 (Reuters) - In May, 2002, Jerome Mitchell, a 17-year old college freshman from rural South Carolina, learned he had contracted HIV. The news, of course, was devastating, but Mitchell believed that he had one thing going for him: On his own initiative, in anticipation of his first year in college, he had purchased his own health insurance.
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« Reply #65 on: March 19, 2010, 10:51:40 AM »
CROI: Clinical Pharmacology at CROI 2010: Advances in Antiretroviral Discovery, Drug Interactions, Compartmental Penetration, and Adverse Reactions - written by Courtney V. Fletcher, Pharm.D. Dean and Professor Colle ge of Pharmacy University of Nebraska Medical Center- (03/14/10)


17th CROI
Conference on Retroviruses and
Opportunistic Infections
San Francisco, CA
Feb 16-19, 2010


Lack of Interaction between Etravirine and Raltegravir plus ...
A pharmacokinetic study was conducted in a subgroup of patients included in the TRIO study to evaluate these parameters. Raltegravir, darunavir, ritonavir ...
www.natap.org/2010/CROI/croi_83.htm


CROI:Darunavir Penetrates Semen Well With High Levels Through 24 Hours -- (02/28/10)


CROI: Darunavir Concentrations in Seminal Pl asma in patients receiving Darunavir/ritonavir(DRV/r) monotherapy: a MONOI-ANRS 136 substudy - (02/28/10)


CROI: Maraviroc Levels in Cerebrospinal Fluid (CSF) and Seminal Plasma from HIV-Infected Patients - (02/28/10)


CROI: Raltegravir Concentrations in the Cervicovaginal Compartment Exceed the Median Inhibitory Concentration in HIV-1-infected Women Treated with a Raltegravir-containing Regimen: DIVA 01 Study - (02/22/10)



CROI:Antiretrovirals for Prevention: Maraviroc Exposure in the Semen and Rectal Tissue of Healthy Male Volunteers after Single and Multiple Dosing - (03/01/10)




CROI: Antiretrovirals For Prevention: tenofovir, FTC, maraviroc; rectal, vaginal, semen. - (03/01/10)
< /span>




CROI: HIV Prevention at CROI 2010 - written by Jared Baeten, MD PhD Connie Celum, MD MPH University of Washington - (03/07/10)
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« Reply #66 on: March 19, 2010, 10:55:04 AM »
CytoDyn, Inc. (Pink Sheets:CYDY) has begun full humanization of Cytolin®, the Company’s unique immune therapy for treating HIV/AIDS.
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« Reply #67 on: March 20, 2010, 11:17:16 AM »
Zocor (simvastatin): increased risk of muscle injury with high doses
Simvastatin is sold as a single-ingredient generic medication and as the brand-name, Zocor. It is also sold in combination with ezetimibe as Vytorin; and niacin as Simcor.
Audience: Primary care providers, patients

FDA notified healthcare professionals and patients that, based on review of data from a large clinical trial and other sources, there is an increased risk of muscle injury in patients taking the highest approved dose of the cholesterol-lowering medication, Zocor (simvastatin ) 80 mg, compared to patients taking lower doses of simvastatin and possibly other drugs in the "statin" class. FDA is also reviewing data from other clinical trials, observational studies, adverse event reports, and data on prescription use of simvastatin to better understand the relationship between high-dose simvastatin use and muscle injury.

Recommendations for healthcare professionals, recommendations for patients and a data summary of information used in this ongoing review are provided in the Drug Safety Communication.

Read the complete MedWatch 2010 Safety summary, including a link to the Safety Communication and current Prescribing Information, at:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAler tsforHumanMedicalProducts/ucm205404.htm



Zocor (simvastatin): increased risk of muscle injury with high doses
Simvastatin is sold as a single-ingredient generic medication and as the brand-name, Zocor. It is also sold in combination with ezetimibe as Vytorin; and niacin as Simcor.
Audience: Primary care providers, patients

[Posted 03/19/2010] FDA notified healthcare professionals and patients that, based on review of data from a large clinical trial and other sources, there is an increased risk of muscle injury in patients taking the highest approved dose of the cholesterol-lowering medication, Zocor (simvastatin) 80 mg, compared to patients taking lower doses of simvastatin and possibly other drugs in the "statin" class. FDA is also reviewing data from other clinical trials, observational studies, adverse event reports, and data on prescription use of simvastatin to better understand the relationship between high-dose simvastatin use and muscle injury.

Recommendations for healthcare professionals, recommendations for patients and a data summary of information used in this ongoing review are provided in the Drug Safety Communication.

[03/19/2010 - Drug Safety Communication - FDA]
[03/2010 - Prescribing Information: Zocor - Merck]
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« Reply #68 on: March 22, 2010, 10:21:38 AM »
Short‐Course Raltegravir Intensification Does Not Reduce Persistent Low‐Level Viremia in Patients with HIV‐1 Suppression during Receipt of Combination Antiretroviral Therapy



Clinical Infectious Diseases March 15 2010;50:912–919



D. McMahon,1 J. Jones,1 A. Wiegand,2 S. J. Gange,3 M. Kearney,2 S. Palmer,2,a S. McNulty,1 J. A. Metcalf,4 E. Acosta,5 C. Rehm,4 J. M. Coffin,2 J. W. Mellors,1 and F. Maldarelli2




1Department of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania; 2HIV Drug Resistance Program, National Cancer Institute–Frederick, National Institutes of Health (NIH), Frederick, 3Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, and 4Clinical Research Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland; and 5Department of Pharmacology, University of Alabama at Birmingham, Birmingham









Background. Combination antiretroviral therapy suppresses but does not eradicate human immunodeficiency virus type 1 (HIV‐1) in infected persons, and low‐level viremia can be detected despite years of suppressive antiretroviral therapy. Short‐course (28‐day) intensification of standard antiretroviral combination therapy is a useful approach to determine whether complete rounds of HIV‐1 replication in rapidly cycling cells contribute to persistent viremia. We investigated whether intensification with the integrase inhibitor raltegravir decreases plasma HIV‐1 RNA levels in patients receiving suppressive antiretroviral therapy.




Methods. Subjects (n=10) with long‐term HIV‐1 suppression receiving combination antiretroviral regimens had their regimens intensified for 4 weeks with raltegravir. Plasma HIV‐1 RNA level was determined before, during, and after the 4‐week intensification period, using a sensitive assay (limit of detection, 0.2 copies of HIV‐1 RNA/mL of plasma). A 4‐week intensification course was chosen to investigate potential HIV‐1 replication in cells with relatively short (about 1–14‐day) half‐lives.




Results. There was no evidence in any subject of a decline in HIV‐1 RNA level during the period of raltegravir intensification or of rebound after discontinuation. Median levels of HIV‐1 RNA before (0.17 log10 copies/mL), during (0.04 log10 copies/mL), and after (0.04 log10 copies/mL) raltegravir intensification were not significantly different (p>.01 for all comparisons in parametric analyses). High‐performance liquid chromatography and mass spectroscopy experiments confirmed that therapeutic levels of raltegravir were achieved in plasma during intensification.




Conclusions. Intensification of antiretroviral therapy with a potent HIV‐1 integrase inhibitor did not decrease persistent viremia in subjects receiving suppressive regimens, indicating that rapidly cycling cells infected with HIV‐1 were not present. Eradication of HIV‐1 from infected persons will require new therapeutic approaches.
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« Reply #69 on: March 22, 2010, 10:22:27 AM »
HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects - pdf attached




   


Nature Medicine | Letter

Nature Medicine  (2010) Received 19 May 2009 Accepted 08 February 2010
Published online 14 March 2010


Maria J Buzón,Marta Massanella,Josep M Llibre,Anna Esteve,Viktor Dahl,Maria C Puertas, Josep M Gatell, Pere Domingo, Roger Paredes,Mark Sharkey,Sarah Palmer,Mario Stevenson, Bonaventura Clotet, Julià Blanco & Javier Martinez-Picado



"In this study, raltegravir intensification revealed the presence of active replication in a large percentage (29%) of subjects on suppressive HAART......Our study also reveals a causal relationship between active replication and immune activation in CD8+ T cells......Longitudinal analysis showed a significant reduction in CD8+ T cell activation markers in the 2-LTR+ subgroup that was particularly evident in CD8+CD45RO+CD38+ T cells (P = 0.047, Fig. 3a). Additionally, the numbers of CD8+HLA-DR+CD45RO+ and CD8+HLA-DR+CD38+ activated cells in the 2-LTR+ subgroup were reduced over time compared to those in the 2-LTR− subgroup...there was also a trend toward a greater increase in absolute CD4+ T cell counts in the 2-LTR+ subgroup at week 24 (P = 0.085; signed rank test), with a larger increase in the percentage of CD4+CD45RA− T cells. These results strengthen the statistical conclusions drawn from the main analysis and indicate that raltegravir is more likely to affect immune activation in people showing altered 2-LTR circle dynamics. This supports the conclusion that residual viral replication, as revealed by 2-LTR circle levels, drives immune activation and that raltegravir intensification can reduce the extent of immune activation by suppressing residual viral replication


"Our study leads us to ask to what extent active replication contributes to viral persistence in HAART. For example, the longevity of the latent reservoir may be partly attributable to continual replenishment by virus produced by active replication. It could be argued that, in the presence of HAART, there is not a complete life cycle within individual infected cells (that is, a cell gets infected but does not make particles) and that the infectious particles are being made by a chronically infected cell that is simply manufacturing virions. However, even in this scenario, conditions would exist for sequence evolution and for viral reservoir replenishment. Therefore, intensification"


ABSTRACT


Highly active antiretroviral therapy (HAART) results in potent and durable suppression of HIV-1 viremia. However, HIV-1 replication resumes if therapy is interrupted1, 2. Although it is generally believed that active replication has been halted in individuals on HAART, immune activation and inflammation continue at abnormal levels3, suggesting continued, low-level viral replication. To assess whether active replication might be driving immune activation in HAART, we examined the impact of treatment intensification with the integrase inhibitor raltegravir on viral complementary DNA and immune activation parameters. In the presence of raltegravir, linear HIV-1 cDNA is prevented from integrating into chromatin and is subsequently converted to episomal cDNAs4, 5. Raltegravir intensification of a three-drug suppressive HAART regimen resulted in a specific and transient increase in episomal DNAs in a large percentage of HAART-suppressed subjects. Furthermore, in subjects with these episomal DNAs, immune activation was higher at baseline and was subsequently normalized after raltegravir intensification. These results suggest that, despite suppressive HAART, active replication persists in some infected individuals and drives immune activation. The ability of raltegravir intensification to perturb the reservoir that supports active replication has implications for therapeutic strategies aimed at achieving viral eradication.

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« Reply #70 on: March 22, 2010, 10:26:10 AM »
Effect of the Intensification with a CCR5 Antagonist on the Decay of the HIV-1 Latent Reservoir and Residual Viremia - see attached full poster report





Reported by Jules Levin
CROI 2010


Carolina Gutiérrez1, L Diaz2, B Hernández-Novoa1, A Vallejo1, C Page1, R Lorente2, N Madrid1, S Palmer3, M Á Muñoz-Fernández2, and S Moreno1

1Hosp Univ Ramón y Cajal, Madrid, Spain; 2Hosp General Univ Gregario Marañón, Madrid, Spain; and 3Swedish Inst of Infectious Diseases Control and Karolinska Inst, Stockholm




Background:  The stability of the CD4 T cell reservoir could be related to continuous replenishment from plasma residual HIV. Intensification with an entry inhibitor could help eliminate detectable levels of ongoing viral replication.




Methods:  Intensification clinical trial (NCT00795444) with maraviroc (MVC) including chronically HIV-infected adults with stable ART consisting of ³3 drugs, and with viral load (VL) <50 copies/mL for ³2 years, CD4 count >350 cells/mm3 and demonstrated CCR5-tropism. Latently-infected resting CD4 cells, residual viremia (RV), and immune activation were determined at baseline (BL) and at week 12 (w12). Latently-infected resting CD4 T cells were quantified using a limiting dilution co-culture assay. RV was measured by quantitative real-time RT-PCR assay (Single Copy Assay, SCA, threshold: 0.3 copies/mL). Enriched episomal 2-LTRs DNA from peripheral blood mononuclear cells was detected by a nested PCR flanking long terminal repeat junction area. Activation was measured on CD4 and CD8 with both anti-HLA-DR and anti-CD38 antibodies (BD Bioscience).




Results:  Nine patients have been included. Median time of HIV diagnosis was 103 months (IQR 58 to 240 months), ART was administered for a median of 75 months (IQR 38 to 144 months), and the median BL CD4 count was 711 cells/mm3 (IQR 547 to 793). At BL, the reservoir could be quantified in 6 of 9 patients (mean 2.04 infectious units per million (IUPM)). At w12 of MVC intensification, all patients maintained VL <50 copies/mL (median CD4 count: 686 cells/mm3 (IQR 589 to 1,005 cells/mm3). A decrease in the latent reservoir was observed in 5 patients, while no decrease was found in one (mean 0.08 IUPM, P =0.048 compared to BL). Even though the BL RNA levels were at the assay limit for 8 of 9 patients, after w12 of intensification viral RNA level increased in 6 patients (range 0.5 to 9.2 copies/mL). Episomal 2-LTRs DNA was undetectable in the 9 patients at BL and turned detectable in 4 of them at w12. A significant decrease in the proportion of CD3+CD4+CD38+HLA-DR+ was observed at wk12 of intensification (median 2.9% (2.5 to 3.3) at BL vs 0.6% (0.4 to 2.4) after intensification, P =0.003. A trend of a decrease in CD3+CD8+CD38+HLA-DR+ was observed after intensification, median 5.4% (4.7 to 7.6) vs 2.3% (0.4 to 2.9), P =0.079.




Conclusions:  In this preliminary analysis, intensification with MVC seems to accelerate the decay of the HIV latent reservoir. Unexpectedly, an increase in RV measured by SCA and episomal 2-LTRs DNA detection has been observed. A decrease in the activation of CD4 and CD8 cells was observed at wk12 of intensification.
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« Reply #71 on: March 22, 2010, 10:26:58 AM »
Antiviral and Immunological Effects of Intensification of Suppressive ART with Maraviroc, a CCR5 Antagonist - see attached full poster report



Reported by Jules Levin
CROI 2010





"As previously reported, levels of immune activation and CD4+ T cell depletion in the GALT persist when compared to PBMC. Thus far, we observe no statistically significant effect of intensification of ART with MVC on a variety of immunologic and virologic parameters in the GALT."


Teresa Evering1, S Mehandru1, M Poles2, P Racz3, K Tenner-Racz3, H Mohri1, N Prada1, D Garmon1, T Parker4, and M Markowitz1

1Aaron Diamond AIDS Res Ctr, The Rockefeller Univ, New York, NY, US; 2New York Univ Sch of Med, NY, US; 3Bernhard Nocht Inst for Tropical Med, Hamburg, Germany; and 4The Rogosin Inst, New York, NY, US




Background:  Gastrointestinal tract CCR5+CD4+ T cells are selectively infected and depleted during acute HIV-1 infection. Despite ART, gut-associated lymphoid tissue (GALT) T cell depletion and activation persists. We hypothesized that ART intensification with the CCR5 antagonist maraviroc (MVC) could effect immune reconstitution and decreased immune activation if this was due to ongoing viral replication during ART.




Methods:  We enrolled adults infected with CCR5-tropic HIV-1 and treated with ART during acute, early infection. Subjects received ART for an average of 4 years prior to study entry and were randomized 2:1 to Arm A, 4 patients whose MVC was intensified for 24 weeks; or Arm B: whose NRTI was intensified for 12 weeks, 2 of whom were followed by cross-over to MVC for 12 weeks. Phlebotomy and flexible sigmoidoscopy with mucosal biopsies were performed at entry, weeks 12 and 24.




Results:  Plasma HIV-1 RNA remained <50 copies/mL for all subjects throughout the study. Gastrointestinal biopsy RNA revealed <50 copies of HIV-1 NL43 gag for all participants at entry through week 24 (mean input of 1.5 x 106 copies of GAPDH/sample). At entry, no significant differences between arms A and B were measured for evaluated parameters. Immunohistochemistry revealed 5.36 ± 0.86 CD4+ T cells/unit area in the lamina propria at entry in Arm A. This did not increase significantly after 24 weeks. In contrast to Arm B, Arm A revealed non-significant decreases (P >0.10) in percentage of proliferating (MIB-1+) CD4+ T cells in the lamina propria between entry and week 12 (11.50% ± 2.50 vs 4.50% ± 1.94) and percentage of proliferating CD8+ T cells in the lamina propria between entry and week 12 (7.50% ± 5.20 vs 3.75% ± 1.11). No further decreases were noted after week 12. In Arm A, flow cytometry revealed significant differences (P <0.02) between the peripheral blood mononuclear cells (PBMC) and gut-associated lymphoid tissue (GALT) at entry in the CD4+CD8+ T cell ratio (1.47 ± 0.14 vs 0.91 ± 0.06) and percentage activated (CD38+) CD8+ T cells (2.61 ± 0.41 vs 17.61 ± 5.02). In Arms A and B, no statistically significant change (P >0.32) was noted in percentage of CD38+ or percentage of proliferating (Ki67+) CD4+ or CD8+ T cells in the GALT between entry, week 12 and week 24. Finally, in both arms, serum endotoxin activity was within the normal range at entry and did not significantly change after 24 weeks.




Conclusions:  As previously reported, levels of immune activation and CD4+ T cell depletion in the GALT persist when compared to PBMC. Thus far, we observe no statistically significant effect of intensification of ART with MVC on a variety of immunologic and virologic parameters in the GALT.
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« Reply #72 on: March 22, 2010, 10:30:35 AM »
ViiV Healthcare Calls for Initial Grant Proposals to the Positive Action for Children Fund

Ten Year Programme to Invest £50million in an effort to Improve the Health and Welfare of Women, Children and Families Affected by HIV

 

Today ViiV Healthcare announced the inaugural request for grant proposals (RFPs) through the Positive Action for Children Fund. Over the next ten years, ViiV Healthcare will invest £50 million in the Fund to support programmes focused on preventing HIV transmission from mother-to-child, as well as the health and well being of women, orphans and vulnerable children around the globe.

“Supporting the most vulnerable populations is core to ViiV Healthcare?s commitment to those affected by HIV and AIDS,” said Dominique Limet, CEO of ViiV Healthcare. “Community-based programmes have long been critical to successful HIV prevention, care and treatment. Through the Positive Action for Children Fund, we are assisting community initiatives tackling the problem of mother-to-child HIV transmission in systemic and sustainable ways.”

Following extensive consultations with some of the sector?s leading non-governmental organisations, practitioners and policy-makers in this field, the Fund will be focused on grants that pursue the four elements of the World Health Organization?s (WHO) strategic vision and comprehensive approach for addressing the mother-to-child transmission of HIV, under these four headings:

1.     Increasing and improving primary prevention of HIV infection among women of childbearing age;

2.     Delivering proper and equitable reproductive choices for people living with HIV/AIDS;

3.     Interventions that prevent HIV transmission from a woman living with HIV to her infant; and

4.     Improving the health and welfare of mothers living with HIV, their children and families by providing appropriate treatment, care and support.
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Offline red_Dragon888

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« Reply #73 on: March 22, 2010, 10:34:41 AM »
http://www.science-n-technology-updates.blogspot.com/2010/03/acne-drug-prevents-hiv-breakout.html

Johns Hopkins scientists have found that a safe and inexpensive antibiotic in use since the 1970s for treating acne effectively targets infected immune cells in which HIV, the virus that causes AIDS, lies dormant and prevents them from reactivating and replicating.

Janice E. Clements, Ph.D. (Credit: Image courtesy of Johns Hopkins Medical Institutions)

The drug, minocycline, likely will improve on the current treatment regimens of HIV-infected patients if used in combination with a standard drug cocktail known as HAART (Highly Active Antiretroviral Therapy), according to research published now online and appearing in print April 15 in The Journal of Infectious Diseases. "The powerful advantage to using minocycline is that the virus appears less able to develop drug resistance because minocycline targets cellular pathways not viral proteins," says Janice Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, vice dean for faculty, and professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine.

"The big challenge clinicians deal with now in this country when treating HIV patients is keeping the virus locked in a dormant state," Clements adds. "While HAART is really effective in keeping down active replication, minocycline is another arm of defense against the virus."

Unlike the drugs used in HAART which target the virus, minocycline homes in on, and adjusts T cells, major immune system agents and targets of HIV infection. According to Clements, minocycline reduces the ability of T cells to activate and proliferate, both steps crucial to HIV production and progression toward full blown AIDS.

If taken daily for life, HAART usually can protect people from becoming ill, but it's not a cure. The HIV virus is kept at a low level but isn't ever entirely purged; it stays quietly hidden in some immune cells. If a person stops HAART or misses a dose, the virus can reactivate out of those immune cells and begin to spread.

The idea for using minocycline as an adjunct to HAART resulted when the Hopkins team learned of research by others on rheumatoid arthritis patients showing the anti-inflammatory effects of minocycline on T cells. The Hopkins group connected the dots between that study with previous research of their own showing that minocycline treatment had multiple beneficial effects in monkeys infected with SIV, the primate version of HIV. In monkeys treated with minocycline, the virus load in the cerebrospinal fluid, the viral RNA in the brain and the severity of central nervous system disease were significantly decreased. The drug was also shown to affect T cell activation and proliferation.

"Since minocycline reduced T cell activation, you might think it would have impaired the immune systems in the macaques, which are very similar to humans, but we didn't see any deleterious effect," says Gregory Szeto, a graduate student in the Department of Cellular and Molecular Medicine working in the Retrovirus Laboratory at Hopkins. "This drug strikes a good balance and is ideal for HIV because it targets very specific aspects of immune activation."

The success with the animal model prompted the team to study in test tubes whether minocycline treatment affected latency in human T cells infected with HIV. Using cells from HIV-infected humans on HAART, the team isolated the "resting" immune cells and treated half of them with minocycline. Then they counted how many virus particles were reactivated, finding completely undetectable levels in the treated cells versus detectable levels in the untreated cells.

"Minocycline reduces the capability of the virus to emerge from resting infected T cells," Szeto explains. "It prevents the virus from escaping in the one in a million cells in which it lays dormant in a person on HAART, and since it prevents virus activation it should maintain the level of viral latency or even lower it. That's the goal: Sustaining a latent non-infectious state."

The team used molecular markers to discover that minocycline very selectively interrupts certain specific signaling pathways critical for T cell activation. However, the antibiotic doesn't completely obliterate T cells or diminish their ability to respond to other infections or diseases, which is crucial for individuals with HIV.

"HIV requires T cell activation for efficient replication and reactivation of latent virus," Clement says, "so our new understanding about minocyline's effects on a T cell could help us to find even more drugs that target its signaling pathways."

The research was supported by grants from the National Institutes of Health.

Authors of the paper, in addition to Clements and Szeto, are Angela K. Brice, Sheila A. Barber and Robert F. Siliciano, all of Johns Hopkins. Also, Hung-Chih Yang of National Taiwan University Hospital.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #74 on: March 24, 2010, 01:37:23 PM »
HIV patients 'at increased community acquired MRSA infection risk'

 
2010-03-24 15:10:00 

 
A new study has shown that HIV-infected patients are at a markedly increased risk for community acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) infections.


In the study, researchers at John H. Stroger, Jr. Hospital of Cook County and Rush University Medical Center found that the incidence of CA-MRSA in the Chicago area was six-fold higher among HIV-infected patients than it was among HIV-negative patients.


Using electronic data, the study authors retrospectively studied HIV-infected patients with CA-MRSA who received medical care during the period of 2000 to 2007 in the regional Cook County Health and Hospitals System. Researchers used patients' zip codes to examine where the cases were distributed geographically.


Overall incidence of CA-MRSA increased significantly for all populations in Cook County from the first period (2000- 2003) to the second period (2004-2007). The incidence increased four-fold from 61 cases to 253 cases per 100,000 HIV-negative patients and nearly four-fold from 411 cases to 1474 cases per 100,000 HIV-infected patients, respectively.


"HIV does not cause CA-MRSA, but our study shows an association between HIV and CA-MRSA. The next steps are to find out what is going on in the community to cause these infections," said study author Dr. Kyle Popovich, an infectious disease specialist at Rush University Medical Center.


"We believe the risk may be amplified by overlapping community-based social networks of high-risk patients," Popovich added.


The study has been published in the April 1 issue of the journal Clinical Infectious Diseases. (ANI)
 
 
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Re: http://natap.org/
« Reply #75 on: March 29, 2010, 01:42:31 PM »
BMS-790052 is a First-in-class Potent Hepatitis C Virus (HCV) NS5A Inhibitor for Patients with Chronic HCV Infection: Results from a Proof-of-concept Study - see attached full poster report

 

Reported by Jules Levin

20th Conference of the APASL, China National Convention Center, 25 – 28 March 2010, Beijing, China. Poster #321

 

Richard E Nettles1, Caly Chien1, Ellen Chung1, Anna Persson1, Min Gao1, Makonen Belema1, Nicholas Meanwell1, Michael DeMicco2, Thomas Marbury3, Ronald Goldwater4, Patrick G Northup5, John Coumbis1, Walter K Kraft6, Michael Charlton7, Juan Carlos Lopez-Talavera1, Dennis M Grasela1.
1Bristol-Myers Squibb, Research and Development, Princeton, NJ; 2Advanced Clinical Research Institute, Anaheim, CA; 3Orlando Clinical Research Center, Orlando, FL; 4PAREXEL International, Baltimore, MD; 5University of Virginia, Charlottesville, VA; 6Thomas Jefferson University, Philadelphia, PA; 7Mayo Clinic, Rochester, MN



AUTHOR CONCLUSIONS
BMS-790052 is a potent NS5A inhibitor that:

– was safe and well tolerated in single doses up to 100 mg

– has a PK profile that potentially supports oncedaily dosing

– produced a robust decline in HCV RNA following a single dose in patients chronically infected with HCV genotype 1







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Re: http://natap.org/
« Reply #76 on: April 02, 2010, 12:45:10 PM »
http://www.dnaindia.com/scitech/report_novel-stem-cell-therapy-to-tackle-hiv_1366070

Novel stem cell therapy to tackle HIV
ANIThursday, April 1, 2010 14:40 IST

Washington, DC: A novel stem cell therapy could in the future be used to treat HIV, say researchers.

Researchers are studying a new approach that arms the immune system with an intrinsic defence against HIV.

While speaking at the Society for General Microbiology's spring meeting in Edinburgh, Professor Ben Berkhout explained how this new approach could dramatically improve the quality of life and life expectancy for HIV sufferers in whom antiviral drugs are no longer effective.

In the absence of an effective vaccine, daily administration of anti-retroviral drugs is the most effective treatment for HIV. However, low patient compliance rates combined with the virus's ability to easily mutate has led to the emergence of drug-resistant strains that are difficult to treat.

Professor Berkhout from the University of Amsterdam is investigating a novel gene therapy that has long-lasting effects even after a single treatment. It involves delivering antiviral DNA to the patients' own immune cells that arms them against viral infection. "This therapy would offer an alternative for HIV-infected patients that can no longer be treated with regular antivirals," he suggested.

The therapy involves extracting and purifying blood stem cells from the patient's bone marrow. Antiviral DNA is transferred to the cells in the laboratory, after which the cells are re-injected into the body. The DNA encodes tiny molecules called small RNAs that are the mirror image of key viral genes used by HIV to cause disease. The small RNAs float around inside the immune cell until they encounter viral genes which they can stick to like Velcro(tm). This mechanism, called 'RNA interference' can block the production of key viral components from these genes.

Transferring the antiviral DNA to stem cells would help to restore a large part of the patient's immune system. "Stem cells are the continually dividing 'master copy' cells from which all other immune cells are derived. By engineering the stem cells, the antiviral DNA is inherited by all the immune cells that are born from it," explained Professor Berkhout.
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« Reply #77 on: April 02, 2010, 12:48:07 PM »
GEOVAX LABS GRANTED ALLOWANCE BY FDA TO START PHASE 1
CLINICAL TRIAL FOR HIV/AIDS THERAPEUTIC VACCINE - attached press release

Company Will Begin Non-Blinded Study in HIV Infected Individuals
Who Started Drug Treatment During Their First Year of Infection

GeoVax Labs, Inc. (OTCBB: GOVX), a biotechnology company  that creates, develops, and tests innovative HIV/AIDS vaccines, is now allowed by the FDA (US Food  and Drug Administration) to begin a phase 1 clinical trial for GeoVax’s therapeutic vaccine, which is  intended as a treatment for individuals infected with HIV (Human Immunodeficiency Virus). The  company will begin a non-blinded study in HIV infected individuals who started drug treatment during  their first year of infection.  An unmet need exists in the market for a HIV  therapeutic vaccine if it can reduce the need for expensive and poorly tolerated lifelong oral medications  currently available to infected individuals.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #78 on: April 02, 2010, 12:49:16 PM »
GSK signs Isis deal, wins EU nod for Duodart

01 April 2010 pharmatimes.com

There was big news from drug giant GlaxoSmithKline yesterday, which won European approval for Duodart and signed a deal with Isis to develop RNA therapeutics for rare diseases.

The UK drugmaker said it has entered into a strategic alliance with US firm Isis Pharmaceuticals, under which the latter?s antisense drug discovery platform will be used to identify and develop new therapeutics against targets for rare and serious diseases, including infectious diseases and some causing blindness.

Opposed to targeting a specific protein in a disease process, antisense therapies actually prevent protein synthesis by elimating the messenger RNA guiding its production. Isis? discovery platform has been constructed to develop specific therapies that bind to mRNA and thereby inhibit the production of disease-causing proteins.

“As a platform, the Isis antisense approach offers us an exciting opportunity to target certain severe diseases in a way that has not previously been possible,” said Patrick Vallance, Senior Vice-President and Head of Drug Discovery at GSK, explaining the group?s interest in the deal. “This new alliance will enhance our discovery platform in this promising research area,” he added.

Under the terms of the deal, which covers up to six programs, Isis stands to receive an upfront cash pile of $35 million, and is also eligible an average of up to $20 million in milestones per program up to the Phase II proof-of-concept stage, at which point GSK can license the compounds if it chooses to and take over all further development and commercialisation.

The deal is certainly huge for Isis, as the group could gain total payments of nearly $1.5 billion if all six programmes are successfully developed in one or more indication, as well as double-digit royalties on sales any product that makes it to market.

Duodart green light
Meanwhile, GSK also announced yesterday that European regulators have waved through Duodart - a fixed dose combination of dutasteride and tamsulosin - for the treatment of moderate-to-severe symptoms of Benign Prostatic Hyperplasia (BPH) and reduction in the risk of acute urinary retention (AUR) and surgery in patients with moderate-to-severe symptoms.

The drug?s approval came on the back of results from the CombAT, which study showed that the combination of dutasteride (marketed as Avodart) and tamsulosin offers patients with moderate-to-severe symptoms of BPH a “significantly superior and sustained symptom improvement” compared with tamsulosin, the most frequently prescribed medication, as well less risk of complications associated with BPH, including a 66% reduction in the risk of AUR and surgery.

According to Eddie Gray, President, Pharmaceuticals Europe at GSK, the firm developed the new fixed-dose combination medicine “to provide patients and physicians a convenient, once-daily treatment, which reduces the impact of the bothersome symptoms of this common condition, and the risk of potential complications and related surgery,” factors which can “create uncertainty and anxiety for many men and may also lead to additional unplanned costs for healthcare providers”.Inline Attachment Follows: 3341017962.txt
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« Reply #79 on: April 02, 2010, 12:51:26 PM »
AIDS ‘Next Big Thing’: Gilead Pill to Prevent Spread



April 01, 2010




April 1 (Bloomberg) -- Gilead Sciences Inc. may learn this year whether its drugs for treating HIV can also stop people from catching the virus in the first place.




The approach may help curb the AIDS pandemic in poor countries and bring Gilead $1 billion a year in additional U.S. sales, said Josh Schimmer, an analyst at Leerink Swann & Co. in Boston. Most investors aren’t alert to the potential benefit, he said. Researchers are compiling the first data from 10 trials involving more than 20,000 people, and initial results may be available in July.




“This could be very meaningful for Gilead,” Schimmer said in a telephone interview. “You’re potentially treating 50 patients to prevent one. Commercially that’s very attractive. I don’t hear anybody talking about this, and I think all of us should be more aware.”




If the strategy works, the pills from Foster City, California-based Gilead may promise the world a powerful tool for fighting AIDS, the deadliest infectious disease, after scientists’ failure so far to develop an effective vaccine or virus-killing gel.




Skeptics say the approach, called pre-exposure prophylaxis, or PrEP, may be too costly and impractical in sub-Saharan Africa, where 22 million people are infected with HIV -- putting millions of others at risk -- and per-capita income is $951 a year.




Side effects may also undermine the plan. While doctors regard Gilead’s drugs as relatively safe, nobody knows what the medicines do in people who are taking them for a disease they don’t have, or how eager these patients will be to put up with the diarrhea, dizziness and depression the pills may cause.




‘High Tolerance’




“People have a high tolerance for side effects if it’s saving their life,” said Mitchell Warren, executive director of the New York-based AIDS Vaccine Advocacy Coalition, a nonprofit advocacy group. “It may be harder for healthy people to accept the side effects that come with prevention.”




The trials involve giving Gilead’s Viread and Truvada, the world’s top-selling AIDS medicine, to HIV-negative people from groups most at risk of contracting the virus, such as gay men who have unsafe sex and drug users who share hypodermic needles. Results from five of the studies may be available this year, according to the researchers running them.




One trial, scheduled to report data at an AIDS conference in July, is testing Viread as a vaginal gel in women who apply it before sex. Another is measuring the preventive effect of a daily Truvada pill among 3,000 gay men in six nations.




A further three studies coordinated by the U.S. Centers for Disease Control and Prevention, based in Atlanta, are testing PrEP among gay men in the U.S., drug users in Thailand and heterosexuals in Botswana. Gilead, while donating drugs and technical advice, isn’t running the trials, the company said.




Behavior Monitored




The studies are also designed to measure whether people receiving the drugs become riskier in their behavior, in the belief they’re protected against the virus. Participants receive testing, condoms and counseling on ways to avoid infection.




If the tests are successful, PrEP distribution programs could begin in developing countries in 2012, said Bill Gates, co-founder of Microsoft Corp. and the Bill & Melinda Gates Foundation, both of Seattle. He spoke to the U.S. Senate Foreign Relations Committee about global health priorities on March 10. The Gates Foundation is sponsoring three PrEP trials.




The CDC would try to issue guidelines on the use of PrEP to health-care providers within six months of successful test results, said Jennifer Horvath, an agency spokeswoman, in an e- mail.




First Defense




“PrEP is the next big thing,” said Warren of the AIDS Vaccine Advocacy Coalition, in a telephone interview. “We have a level of biological plausibility and early data in animal studies that is stronger than anything we have seen in the other approaches.”




Gilead had revenue of $7.01 billion last year, including sales of $5.54 billion from its top three AIDS drugs -- Truvada, Atripla and Viread -- which are taken by 85 percent of HIV patients in the U.S. as a first defense against the virus.




Gilead rose 17 cents, or less than a percent, to $45.64 at 4 p.m. New York time in Nasdaq Stock Market composite trading. The shares have increased 1 percent in 12 months. Investors aren’t sure what to make of the PrEP trials, said Jason Kantor, an analyst at RBC Capital Markets in San Francisco.




“This is not currently a focus for investors, and I have nothing in my estimates for this,” Kantor said an e-mail. “Positive data, if compelling, could be a small incremental benefit in the developed countries.”




Implications Unknown




PrEP sales in the U.S. may range from “negligible” to as much as $1 billion annually, depending on the effectiveness of the drugs and how much patients and public-health agencies are willing to pay for prevention, Leerink’s Schimmer said.




Gilead itself doesn’t know what the commercial implications of PrEP might be, said Jim Rooney, the company’s director of clinical affairs.




“It’s going to depend upon the data,” Rooney said in a phone interview. “And it’s going to depend upon how the public- health officials evaluate the data and translate that into recommendations for clinical practice.”




Gilead will decide whether to seek regulatory approval of its drugs for prevention once results of the trials are known, Rooney said.




Doctors would be able to prescribe the medicines for prevention without the approval. A study published last year in the Journal of Acquired Immune Deficiency Syndromes found that among 277 gay men in Boston, one had used PrEP and 74 percent said they would use it if it were available.




Breast Milk




Drugs made by GlaxoSmithKline Plc of London and Boehringer Ingelheim GmbH of Ingelheim, Germany, are already used to prevent infected mothers from passing the virus to their babies in the womb or through breast milk. Glaxo’s Combivir is prescribed to prevent infections in men who take it after unprotected sex with an HIV-positive partner.




Those medicines show that using treatments as prevention can work, said Dawn Smith, a CDC researcher who is devising the agency’s plans to implement PrEP if the clinical trials succeed.




“I’m very hopeful that this approach will help to reduce HIV infection rates,” Smith said in a telephone interview. “But I’m enough of a scientist to be skeptical as well, and to want to see the trial results before I call myself a believer.”




Gilead’s drugs subdue HIV in infected patients by blocking an enzyme the virus needs to hijack cells in order to reproduce. Taken preemptively, the pills may prevent HIV from gaining a foothold when it first enters the body.




‘Good Reason’




A study presented at the Conference on Retroviruses & Opportunistic Infections, in Montreal last year, found Truvada cut the risk of infection almost 16-fold in monkeys. A 2007 trial of PrEP among 936 women in Africa concluded that a daily Viread pill cut the risk of infection by 65 percent, though the researchers said the trial didn’t produce enough data to prove conclusively that PrEP worked.




“From a scientific standpoint, there really is a good reason to believe that if properly done, it will work,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, based in Bethesda, Maryland, said at this year’s retroviruses conference, held in San Francisco in February.




There may be less reason to think PrEP is feasible, Fauci said.




“If we can’t get 70 percent of the people who are infected in low- and middle-income countries on therapy, how are we going to get people who aren’t even infected on therapy?” Fauci said.




If it does work, PrEP won’t come cheap. Giving Truvada to the 100,000 most at-risk gay men in the U.S. would cost more than $1 billion a year, the CDC said on its Web site. That sum covers only the cost of the pills, and doesn’t include marketing, HIV testing, and doctors’ visits.




‘Deep Down Horror’




Identifying people who are at sufficient risk of contracting HIV to receive PrEP will most likely be too difficult in Africa, where everyone who is sexually active is at risk, said Francois Venter, president of the Southern African HIV Clinicians Society, a professional group based in Johannesburg.




“Deep down I have this horror that we’ll have an effective intervention very few people are going to use,” Venter said in a telephone interview. “In America and Europe it’s probably going to be one of several interventions which are going to work. I worry that there hasn’t been enough focus on who’s going to take these drugs in my environment.”




To justify the expense of handing out drugs to people who don’t have HIV, the trials need to show that PrEP lowers the chances of infection by at least half, said Francoise Barre- Sinoussi, a French researcher who shared the 2008 Nobel Prize in medicine after helping to discover that HIV causes AIDS.




‘Little Bit Concerned’




“We will have encouraging information from those trials,” Barre-Sinoussi said in an interview in Singapore. “I’m just a little bit concerned about how to apply it at large scale.”




About 33 million people live with HIV, according to UNAIDS, the coalition of United Nations agencies formed to fight HIV. In 2008, 2.7 million people were newly infected with the virus and 2 million died from AIDS-related complications. Africa has 7 in every 10 of the world’s cases.




Assuming PrEP could prevent 50 percent of infections, it would almost cut in half the lifetime risk of catching HIV among high-risk gay men in the U.S., and almost triple the lifetime treatment costs, according to a computer simulation published in the journal Clinical Infectious Diseases in March 2009.




PrEP is “unlikely to confer sufficient benefits to justify the current costs” of Truvada in the U.S., researchers from Yale University in New Haven, Connecticut, and Harvard Medical School in Boston wrote in the study. The model assumed a drug cost of $753 a month for each patient.




Drug Costs




Gilead sells a month’s supply of Viread to U.S. wholesalers for about $643. A month of Truvada costs about $930, said Cara Miller, a company spokeswoman, in an e-mail. The company charges people in poor countries about $17 a month for Viread and $26 for Truvada, she said. About 700,000 people worldwide take brand-name or generic versions of Gilead’s AIDS drugs, Miller said.




When the first AIDS drugs were approved in the U.S. in 1987, critics said they weren’t affordable in poor nations, the CDC’s Smith said. Now, about 40 percent of the patients who need them are getting the medicines, according to UNAIDS. PrEP may also prove more adoptable than its critics think, Smith said.




“If it’s highly efficacious, and if countries and UNAIDS and WHO and other public health agencies believe that it has a role to play in reducing new HIV infections, then we will find a way to make it available,” Smith said.
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Re: http://natap.org/
« Reply #80 on: April 03, 2010, 11:19:44 AM »
http://www.advocate.com/News/Daily_News/2010/04/02/Stem_Cell_Transplant_Patient_Free_of_HIV/

Stem Cell Transplant Patient HIV-Free

By Julie Bolcer



A 42-year-old HIV patient with leukemia continues to show no signs of HIV in his blood, two years after a stem cell transplant from a donor with a gene mutation that confers natural resistance to the virus that causes AIDS.

The stunning findings were published Wednesday in The New England Journal of Medicine, according to CNN, but doctors caution that the stem cell treatment is too dangerous to be of routine use to most people infected with HIV.

In the study, reported CNN, “the team deliberately chose a compatible donor who has a naturally occurring gene mutation that confers resistance to HIV. The mutation cripples a receptor known as CCR5, which is normally found on the surface of T cells, the type of immune system cells attacked by HIV.

“The mutation is known as CCR5 delta32 and is found in 1 percent to 3 percent of white populations of European descent.

“HIV uses the CCR5 as a co-receptor (in addition to CD4 receptors) to latch on to and ultimately destroy immune system cells. Since the virus can't gain a foothold on cells that lack CCR5, people who have the mutation have natural protection. (There are other, less common HIV strains that use different co-receptors.)

“People who inherit one copy of CCR5 delta32 take longer to get sick or develop AIDS if infected with HIV. People with two copies (one from each parent) may not become infected at all. The stem cell donor had two copies.”

Doctors say that while the risky stem cell transplant option should not be routinely exercised, the findings point the way toward development of potentially safer CCR5-disabling gene therapies or treatments that can be injected into the body.

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« Reply #81 on: April 03, 2010, 01:03:28 PM »
Asian Liver Conference (APASL) March 25-28 2010


At the meeting just completed this year there were a bunch of new study results presented on the use of Pegasys for HBV with links to study results below. As well, there were updates with 3-year followup on tenofovir for HBV, and new entecavir studies including in patients with hepatic decompensation, and several studies from BMS reporting on 3 new HCV drugs they are developing: the NS5A inhibitor BMS790052, the protease inhibitor BMS6 50032, and their new lambda interferon which in early studies shows less side effects than standard peginterferon with similar antiviral activity. Jules Levin


APASL: Treatment of HBeAg-positive CHB infection with peginterferon alfa-2a [40KD] (PEGASYS) plus lamivudine or adefovir for 96 weeks results in high rates of HBsAg clearance / seroconversion - (03/31/10)


APASL: Identification of a baseline algorithm to select chronic hepatitis B patients for therapy with peginterferon alfa-2a [40KD] (PEGASYS) - (03/31/10)


APASL: A pilot study of interferon alpha/peginterferon alfa-2a combined with response-guided short-term nucleoside analog therapy in HBeAg-positive hepatitis B patients- (03/31/10)


APASL: On-Treatment Decline in Serum HBsAg Levels Predicts Sustained Immune Control 1 Year Post-Treatment and Subsequent HBsAg Clearance in HBeAg-Negative Hepatitis B Virus-Infected Patients Treated with Peginterferon Alfa-2a [40KD] (PEGASYS) - (03/31/10)


APASL: On-Treatment Decline in Serum HBsAg Level s Predicts Sustained Immune Control and HBsAg Clearance 6 Months Pos t-Treatment in HBeAg-Positive Hepatitis B Virus-Infected Patients Treated with Peginterferon Alfa-2a [40KD] (PEGASYS) - (03/31/10)


APASL: Sustained Immune Control 1 Year Post-Treatment with Peginterferon Alfa-2a [40KD] (PEGASYS) is Durable up to 5 Years Post-Treatment and is Associated with a High Rate of HBsAg Clearance in HBeAg-Negative Chronic Hepatitis B - (03/31/10)


APASL: Large International, Observational Study of Patients with Chronic Hepatitis B Infection Treated with Peginterfe ron Alfa-2a [40KD] (PEGASYS): the S-Collate Cohort - (03/31/10)
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« Reply #82 on: April 05, 2010, 02:06:06 PM »
SCYNEXIS Announces Acceptance of Abstracts Related to its Hepatitis C Clinical Candidate, SCY-635, for Presentation at 45th Annual Meeting of the European Association for the Study of the Liver

RESEARCH TRIANGLE PARK, N.C. --(Business Wire)-- Drug discovery company, SCYNEXIS, Inc. today announced that multiple abstracts related to the Company's cyclophilin inhibitor, SCY-635, were accepted for presentation at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria, April 14-18, 2010. SCY-635, a cyclophilin inhibitor, represents a new class of drugs for the treatment of hepatitis C virus (HCV) infection and is the first candidate from a broad platform of proprietary cyclophilin inhibitors developed by SCYNEXIS. Full abstracts can be viewed at the EASL website at www.easl.eu.
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Offline red_Dragon888

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« Reply #83 on: April 05, 2010, 02:07:02 PM »
we found high levels of mistrust about HIV treatment and the governments' role in the HIV epidemic. Adherence rates were generally low.....HIV conspiracies cannot be dismissed as rare or extreme. Such beliefs can ultimately contribute to decreased survival time



The present study was conducted among African American men with HIV in the Los Angeles, CA, area. We recruited 214 African American men with HIV on antiretroviral treatment using fliers disseminated and posted by staff at 3 HIV social service agencies and an HIV medical clinic........Almost two-thirds (64%) agreed with at least 1 HIV conspiracy belief; about half (48%) agreed with 2 or more. Forty-four percent believed that HIV is manmade, 35% thought that AIDS was created in a government laboratory, and a third endorsed the genocidal belief related to a cure being withheld (Table 1). Conspiracy beliefs about medications were also substantially endorsed, with 22% believing that people who take the new HIV medications are human guinea pigs for the government and 17% believing that the medications are poison. Participants who screened positive for depression and who had higher incomes were more likely to endorse at least 1 conspiracy belief.....On average, participants took only 68% of the prescribed doses of their HIV antiretroviral medications during the month between the baseline and follow-up assessments (Table 2). Only 22% of participants demonstrated an optimal level of adherence (ie, ≥95% of doses)



Conspiracy Beliefs About HIV Are Related to Antiretroviral Treatment Nonadherence Among African American Men With HIV



JAIDS Journal of Acquired Immune Deficiency Syndromes:

April 2010 - Volume 53 - Issue 5 - pp 648-655



Bogart, Laura M PhD; Wagner, Glenn PhD; Galvan, Frank H PhD; Banks, Denedria MSW

From the *Children's Hospital Boston/Harvard Medical School, Department of Medicine, Division of General Pediatrics, Boston, MA; †RAND Corporation, Health Program, Boston, MA; and ‡Charles Drew University of Medicine and Science, Institute for Community Health Research, Los Angeles, CA.



Abstract




Background: Medical mistrust is prevalent among African Americans and may influence health care behaviors such as treatment adherence. We examined whether a specific form of medical mistrust-HIV conspiracy beliefs (eg, HIV is genocide against African Americans)-was associated with antiretroviral treatment nonadherence among African American men with HIV.
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Offline red_Dragon888

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« Reply #84 on: April 05, 2010, 02:07:55 PM »
The Impact of Transmitted Drug-Resistance on Treatment Selection and Outcome of First-Line Highly Active Antiretroviral Therapy (HAART)



JAIDS Journal of Acquired Immune Deficiency Syndromes:

April 2010 - Volume 53 - Issue 5 - pp 633-639



Bansi, Loveleen MSc; Geretti, Anna Maria MD; Dunn, David PhD; Hill, Teresa PhD; Green, Hannah MSc; Fearnhill, Esther; Gazzard, Brian Prof; Nelson, Mark MD; Porter, Kholoud PhD; Phillips, Andrew Prof; Sabin, Caroline Prof; and on behalf of the UK Collaborative Group on HIV Drug Resistance UK Collaborative HIV Cohort (CHIC) Study

From the *University College Medical School, London, United Kingdom; †Royal Free Hampstead NHS Trust, London, United Kingdom; ‡Medical Research Council Clinical Trials Unit, London, United Kingdom; and §Chelsea and Westminster Hospital, London, United Kingdom.



Abstract




Objective: The study aim was to determine how resistance testing influences outcome of first-line highly active antiretroviral therapy (HAART) in routine practice in the United Kingdom.




Methods: The prevalence of transmitted drug resistance and the genotypic sensitivity score (GSS) of first-line HAART regimens were determined using data from the UK Collaborative HIV Cohort (CHIC) Study. Factors associated with starting a regimen with a reduced GSS and subsequent virological responses were analyzed by logistic and Cox regression.

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Offline red_Dragon888

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« Reply #85 on: April 05, 2010, 02:09:22 PM »
Overall, 21.0% (232,700; 95% CI = 221,200-244,200) of estimated prevalent HIV cases were undiagnosed.....The highest percentage of undiagnosed HIV (26.7%) was among men with a transmission category of high-risk heterosexual contact (HRHC), defined as reporting heterosexual contact specifically with a person known to have, or to be at high risk for, HIV infection (eg, an injection drug user). The second highest percentage of undiagnosed HIV was among MSM (23.5%).



Undiagnosed HIV Prevalence Among Adults and Adolescents in the United States at the End of 2006



JAIDS Journal of Acquired Immune Deficiency Syndromes:

April 2010 - Volume 53 - Issue 5 - pp 619-624



Campsmith, Michael L DDS, MPH; Rhodes, Philip H PhD; Hall, H Irene PhD; Green, Timothy A PhD

From the Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA.



Abstract




Objectives: To describe adults/adolescents (age 13 years and older) living with undiagnosed HIV infection in the United States at the end of 2006.




Methods: HIV prevalence and percentage undiagnosed were estimated from cumulative HIV incidence using an extended back-calculation model (using both HIV and AIDS data, the time of first diagnosis with HIV, and disease severity at diagnosis) and estimated cumulative deaths.
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« Reply #86 on: April 05, 2010, 02:10:32 PM »
Prescription-Drug Sales Rise 5.1%



Revenue, Usage Increase as Drug Makers, Retailers Offer Discounts on Co-Pays



By JONATHAN D. ROCKOFF April 2 2010




Spending on prescription drugs topped $300 billion in the U.S. last year, rising 5.1% despite the economic downturn, according to IMS Health. But the rate of growth was at the low end of historical levels, reinforcing the difficulties brand-name drug makers face relying on the U.S. market to increase revenue.




The number of prescriptions dispensed in the U.S. also edged higher last year, increasing 2.1% to 3.9 billion, IMS Health reported Thursday. IMS Health collects data from drug makers, pharmacies and other sources and advises companies on health-care trends.






The results underscore the "resilience" of prescription-drug demand in the face of a down economy, said Murray Aitken, a senior vice president at IMS Health. In 2008, the spending rose just 1.8%, only the third time since 1957 the rate of growth was below 5%.




Investors have traditionally viewed pharmaceutical stocks as good options during down economies, although some companies, such as Merck & Co., said the recent recession was damping sales.




Still, the data pointed to concerns for branded drug makers. The number of prescriptions dispensed for generic drugs rose 5.9% last year, but those for branded drugs declined 7.6%. Of all prescriptions dispensed, 75% were for generics last year, up from 57% five years earlier.




Partly due to the rising use of those generics, prescription-drug spending managed to increase overall for the year to $300.3 billion, Mr. Aitken said. Drug makers and retailers also encouraged prescription-drug use by offering patients discounts on co-pays and other incentives. Slightly higher prices for certain brand-name treatments also contributed to higher revenue.




IMS Health said it couldn't specify how much the prices for brand-name drugs increased.




Sales of brand-name drugs are expected to keep rising at relatively low rates in the mid-single digits, Mr. Aitken said. Making matters difficult for brand-name drug makers, several of their top-selling medicines, including Pfizer Inc.'s popular Lipitor, are scheduled to lose patent protection over the next few years.




One sign of the problems ahead for branded drug companies was in the results for cholesterol-fighting drugs. They continued to be the largest class of prescription medicines by prescription volume. But they dropped to third place from second in terms of overall sales, due to rising use of generic versions.




Antipsychotic medicines were the top-selling class of drugs in the U.S. last year, with sales of $14.6 billion. Proton-pump inhibitors were second with sales of $13.6 billion, IMS Health said.
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« Reply #87 on: April 05, 2010, 02:11:22 PM »
CROI: Prolonged Control of Viremia After Transfer of Autologous CD4 T Cells Genetically Modified with a Lentiviral Vector Expressing Long Antisense to HIV env (VRX496) - (04/03/10)

In an ongoing phase I/II trial, 17 HIV-1-infected subjects who were fully suppressed on ART received over a period up to 14 weeks 3 or 6 infusions each of 10 to the 10th autologous CD4 T cells transduced with a lentiviral vector encoding a 937 nucleotide HIV env antisense construct (VRX496) and expanded ex vivo. To evaluate the effects this therapy had on viral set points and CD4 counts, eligible subjects underwent scheduled treatment interruption (STI) six weeks after the last infusion.
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« Reply #88 on: April 06, 2010, 11:00:05 AM »
Canadian payers “reject over 50% of new drugs each year”

06 April 2010
pharmatimes.com

Every year, Canada’s centralised review body, the Common Drug Review (CDR), rejects the majority of new drugs put forward for coverage by the nation’s publicly-funded drug plans, largely because their makers have failed to address problems raised by other health technology assessment agencies (HTA) such as NICE, a leading expert says.

Moreover, for almost all products which the CDR does recommend, the decision comes with restrictions, Neil Palmer, president of pricing and reimbursement consultancy PDCI Market Access, told a recent conference in London.

The drug plans run by Canada’s 10 provinces and three territories account for 45% of the nation’s total spending on prescription drugs, and their share reached an estimated C$11.4 billion in 2009, according to the Canadian Institute for Health Information (CIHI). The CDR advises the plans (apart from Quebec’s) as to which products they should cover, based on clinical and pharmacoeconomic reviews but not budget impact - this is assessed by each individual plan.

The provinces have been slow to implement positive CDR recommendations largely because of budget concerns, but they have begun addressing these through negotiating various types of agreements with manufacturers, and in some provinces such deals are now a requirement for listing, Mr Palmer told the conference, which was organised by Health Network Communications.

For example, Ontario’s Transparent Drug System for Patients Act of 2006 created an “executive officer” position that could negotiate and implement agreements with manufacturers.

A number of studies have concluded that the CDR is “more restrictive” than other HTA agencies, said Mr Palmer. For example a recent comparison of the decisions taken for 64 drugs by the CDR and the Scottish Medicines Consortium (CMR) found that the Canadian agency recommended just 1.6% of the products for listing, while the SMC recommended 34.4%. The percentages for “list with restrictions” and “do not list” were 51.6% and 46.9% respectively for the CDR, compared with 43.8% and 21.9% for the Scottish agency.

Analysis suggests that the CDR “is unconvinced” that new products offer incremental value when older, less expensive alternatives are available. And, while Canada has no official incremental cost-effectiveness ratio threshold, the probability of rejection increases speedily once it goes over C$50,000 per Quality-Adjusted Life Year (QALY) and is almost certain above C$70,000 per QALY, said Mr Palmer.

- Health Canada takes an average of 388 days to approve a new drug, after which the provinces take a further 316 days to decide whether to include it on their drug programmes. Moreover, by the end of 2009, only 23% of new drugs approved by Health Canada in 2004 had been approved for either full or partial reimbursement under provincial drug plans, according to a report published last month by Canadian free-market think tank The Fraser Institute.

“In the end, the provinces usually choose not to cover these drugs, leaving the one-third of Canadians who rely on provincial drug plans without access to most new medicines,” said report co-author Mark Rovere, a senior policy analyst at the Institute.

One solution to this problem, he suggests, could be for Canada to take better advantage of the regulatory knowledge and capacity of other jurisdictions, rather than attempting to duplicate the drug approval process used by the US Food and Drug Administration (FDA). By entering into agreements of mutual recognition with other countries, new medications already approved in those countries could be introduced into the Canadian market far more rapidly, he proposes.

Moreover, the report says, the most economically rational way to improve access to new medicines without increasing the burden on taxpayers would be to replace the publicly-funded drug programmes with means-tested, subsidised access to a “a properly regulated, competitive private-sector insurance market.”

“The best policy choice for improving access to the newest prescription drugs is to allow the private insurance market to compete through price and service,” says Mr Rovere.
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« Reply #89 on: April 08, 2010, 04:03:13 PM »
Vitamins C and E: No benefit in pregnancy-associated hypertension
April 7, 2010 | Lisa Nainggolan


Pittsburgh, PA - The largest study so far to examine the use of antioxidant doses of vitamins C and E to prevent the complications of pregnancy-associated hypertension, including preeclampsia, has found no benefit of this approach [1].


"The bottom line was that within the groups of women we studied, using the same doses of vitamins C and E that were used in all other studies, the groups are virtually superimposable—as far as every primary and secondary outcome, they are almost indistinguishable; there is no evidence of any benefit," lead author Dr James Roberts (University of Pittsburgh, PA) told heartwire. He and his coauthors report their findings in the April 8, 2010 issue of the New England Journal of Medicine.


"Women should continue to take prenatal supplements, which have these vitamins in them but at a fraction of the dose," he continued. "But there is no justification for recommending these medications to try to prevent preeclampsia or to try to prevent the complications of preeclampsia at this time," he commented.

No benefit of vitamins on primary outcome or any secondary end points



Roberts explained that the idea that oxidative stress is involved in the development of preeclampsia gained ground during the late 1990s, when a small study involving high-risk women showed a 60% reduction in diagnosis of preeclampsia with supplementation with antioxidant doses of vitamins C and E compared with placebo.


This prompted several other groups to examine this issue, but none were able to replicate the original positive findings.


Roberts said this new study was unique among trials in this field in that they decided the end point would not be a diagnosis of preeclampsia but rather whether the vitamins had any effect on new-onset pregnancy-associated hypertension. This meant they could assess whether the therapy would prevent serious complications rather than merely modify diagnostic findings, he explained.


The multicenter, randomized, double-blind trial conducted between July 2003 and February 2009 involved nulliparous women at low risk for preeclampsia who were randomly assigned to 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo between the ninth and 16th weeks of pregnancy. Therapy in this study was initiated at an earlier stage of gestation than in any of the previous trials, Roberts noted.


The primary outcome was severe pregnancy-associated hypertension alone or severe or mild hypertension with elevated liver enzymes, thrombocytopenia, elevated serum creatinine levels, medically induced preterm birth, fetal-growth restriction, or perinatal death.


Outcome data were available for 9969 women; there was no significant difference between the vitamin and placebo groups in the rates of the primary outcome (6.1% and 5.7%, respectively; relative risk 1.07) or in the rates of preeclampsia (7.2% and 6.7%; relative risk 1.07), a major secondary outcome.


There was also no evidence of a benefit with vitamin therapy with respect to any of the other prespecified secondary outcomes, the researchers note.

Vitamins associated with slight increase in BP, but not low birth weight



On a positive note, there was no evidence of an excess of low-birth-weight babies among those taking the vitamin supplements in this study, said Roberts, something that was found in a previous trial, the UK Vitamins in Preeclampsia (VIP) study.


But researchers did find a slight increase in blood pressure in the women who took vitamins, a finding that was also observed in the VIP study and a similar Australian trial, said Roberts.


"The expectation [was a lowering of BP], but in all three studies not only was there not a reduction, there was actually an excess of higher blood pressure, but not of preeclampsia. So there is something to suggest that either vitamin C or E might have an effect on BP to increase it slightly, but other than that we had no adverse outcomes in our study," Roberts noted.

Vitamins C and E not the answer, but oxidative stress may still play a role



"It's definitely established that the drugs we gave at the doses we gave, when we gave them, did not reduce any of the problems in either high- or low-risk patients when you put all the studies together," Roberts said.


He also noted that these vitamins didn't work in cardiovascular-disease prevention, either: "The cardiovascular literature suggests C and E are not the answer if antioxidants are valuable."
However, he still believes that oxidative stress somehow plays a role in the development of preeclampsia: "People haven't completely given up on the fact that oxidative stress—which is what we were treating with those vitamins—is part of the disease, and we will continue to look for a group that might have benefit."


There are also a couple of trials starting in the UK looking at other antioxidants—selenium, for example, he notes. "Beyond oxidative stress, inflammation is an interesting area, and there is some suggestion that statins may be useful, and there may be a small trial going on."

Second, smaller study replicates findings



A second, smaller study has also found that antioxidant supplementation with the same doses of vitamins C and E did not reduce the rate of preeclampsia or gestational hypertension in almost 2500 women [2]. The study was stopped early, partly because of an increased risk of fetal loss or perinatal death in those treated with the vitamins as opposed to the women who received placebo, although the difference between the two was not statistically significant, say Dr Hairong Xu (University of Montreal, QC) and colleagues in their paper in the March 2010 issue of the American Journal of Obstetrics & Gynecology.


"Vitamin-C and -E supplementation at the above doses cannot be recommended for pregnant women to prevent adverse pregnancy outcomes including preeclampsia," they conclude.


Financial and other disclosures provided by the authors of the New England Journal of Medicine paper are available with the full text of this article at NEJM.org. No disclosures are listed for the paper in the American Journal of Obstetrics & Gynecology.
 

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Sources
Roberts JM, Myatt L, Spong CY, et al. Vitamins C and E to prevent complications of pregnancy-associated hypertension. New Engl J Med 2010; 362:1282-1291.
Xu H, Perez-Cuevas R, Xiong X, et al. An international trial of antioxidants in the prevention of preeclampsia (INTAPP). Am J Obstet Gynecol 2010; 202:239.e1-239.e10. 
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Offline red_Dragon888

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« Reply #90 on: April 08, 2010, 04:04:18 PM »
Higher Darunavir and Raltegravir Levels in Small Study of People With Liver Disease

11th International Workshop on Clinical Pharmacology and HIV Therapy, April 7-9, 2010, Sorrento
Mark Mascolini

Levels of darunavir and raltegravir, both mainly metabolized by the liver, were higher in HIV-infected people with moderate to severe liver disease than in a comparison group of HIV-positive people without liver problems [1]. Darunavir troughs were substantially higher in people with cirrhosis than in people with more moderate liver impairment.

This small case-control study involved 5 Caucasian men coinfected with HIV and hepatitis C virus (HCV) who started a regimen containing both the integrase inhibitor raltegravir and the protease inhibitor darunavir. Researchers at Rome's INMI Lazzaro Spallanzani Infectious Diseases Department collected blood samples from these 5 men 14 and 30 days after their started their raltegravir/darunavir-based regimen. They compared raltegravir and darunavir levels in these men with levels in 24 people without HCV who were taking these two drugs for HIV.

The 5 HIV/HCV-coinfected men averaged 48 years in age (+/- 5 standard deviation). They had been infected with HIV for an average 16 years and had an average lowest-ever CD4 count of 58 and an average body mass index of 23 kg/m(2) (+/- 1.3). Along with raltegravir and darunavir, 2 men were taking a second protease inhibitor, 2 were taking two nucleosides, and 1 was taking a nonnucleoside. Ultrasonography indicated that 3 men had cirrhosis (Child Pugh stage B) and 2 had chronic active HCV-related hepatitis.

Raltegravir trough concentrations averaged 637 ng/mL in the men with liver impairment versus 221 ng/mL in the HCV-negative controls. The 3 men with cirrhosis had a raltegravir trough of 665 ng/mL, compared with 581 ng/mL in the 2 HIV/HCV-coinfected men without cirrhosis.

Darunavir troughs in coinfected men averaged 8519 ng/mL, compared with 3236 ng/mL in the control group. Darunavir troughs averaged 9820 ng/mL in the 3 men with cirrhosis versus 2016 ng/mL in the 2 coinfected men without cirrhosis.

Virologic and immunologic results were similar in the 3 men with cirrhosis and the 2 without cirrhosis, and antiretroviral safety over the course of this study did not differ between these two groups. One of the men with cirrhosis died 1 month after starting the raltegravir/darunavir regimen because of acute liver and kidney disease.

On the basis of this small case-control comparison, the investigators suggest "special caution in the use of raltegravir, and especially of darunavir, in patients with moderate to severe liver impairment because of the risk of additive toxicity."

US prescribing information already advises clinicians to "monitor liver function before and during therapy [with darunavir/ritonavir], especially in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases." For raltegravir, US prescribing information cites "no clinically important pharmacokinetic differences between subjects with moderate hepatic impairment and healthy subjects" but cautions that "the effect of severe hepatic impairment on the pharmacokinetics of raltegravir has not been studied."

Reference
1. Tommasi C, Nicastri E, Gallo AL, et al. Raltegravir and darunavir plasma pharmacokinetic in HIV-1 infected patients with advanced liver disease. 11th International Workshop on Clinical Pharmacology and HIV Therapy. April 7-9, 2010. Sorrento. Abstract 10.
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« Reply #91 on: April 08, 2010, 04:05:01 PM »
Women With Tight HIV Control Have Higher Antiretroviral Troughs Than General Population

11th International Workshop on Clinical Pharmacology and HIV Therapy, April 7-9, 2010, Sorrento
Mark Mascolini

Among Canadian women with an undetectable viral load, minimum concentrations (Cmins) of four antiretrovirals were 22% higher than in a mostly male general-population comparison group [1]. Unboosted or boosted atazanavir maximum concentrations (Cmax) were substantially lower in women than in the general population, and nevirapine Cmins were much higher. Overall, Cmins were highly variable within and between antiretrovirals.

Previous research has found higher antiretroviral concentrations in women than in men, but research on this issue is limited. To get a better fix on concentrations of four major antiretrovirals in women with an undetectable viral load, Charles la Porte and colleagues at 14 Canadian sites conducted a cross-sectional study of 83 women taking their first regimen. The researchers collected timed blood samples weekly for 3 weeks. They compared median Cmax and Cmin in individual women with published average Cmax and Cmin from a general population group consisting mostly of men.

The investigators excluded women with poor antiretroviral adherence, pregnant or breastfeeding women, those not taking standard doses, and those with end-stage organ disease, other significant non-HIV disease, or malignancy requiring chemotherapy.

The 83 women had a median age of 42 years (interquartile range [IQR] 36 to 48) and a median current CD4 count of 490 (IQR 380 to 640). Median weight stood at 67.3 kg (IQR 60.3 to 81.7) and median body mass index at 25.5 kg/m(2) (IQR 22.3 to 31.0). Women had taken their first antiretroviral regimen for a median of 3.8 years (IQR 1.8 to 7.8).

Ten women were taking unboosted atazanavir, 18 boosted atazanavir, 20 lopinavir, 16 efavirenz, and 19 nevirapine.

Overall median antiretroviral Cmin was 22% higher in these women than in the general population group (ratio 1.22, IQR 0.72 to 1.93). That difference was driven by lopinavir (ratio 1.22, IQR 0.79 to 1.81) and nevirapine (ratio 1.62, IQR 0.91 to 2.32). But the study disclosed no significant predictors of high Cmin.

Median Cmax was 14% lower in the women than in the general population (ratio 0.86, IQR 0.59 to 1.25), and that difference could be traced primarily to unboosted atazanavir (ratio 0.53, IQR 0.28 to 0.94), boosted atazanavir (ratio 0.67, IQR 0.54 to 0.85), and efavirenz (ratio 0.79, IQR 0.57 to 1.27).

Percentages of women with a Cmin more than 1.5 times above the population average were 20.0% for unboosted atazanavir, 27.8% for boosted atazanavir, 30.0% for lopinavir, 37.5% for efavirenz, and 52.6% for nevirapine. Percentages of women with a Cmax more than 1.5 times above the population average were 0% for boosted or unboosted atazanavir, 25.0% for lopinavir, 25.0% for efavirenz, and 15.8% for nevirapine.

Within-patient variability for Cmin and Cmax were greatest for unboosted atazanavir (52.3 and 63.9) and lowest for efavirenz (17.7 and 15.5) and nevirapine (17.5 and 15.7)

Black women tended to have a lower Cmin/population Cmin (-0.16, P = 0.08), as did injecting drug users (-0.22, P = 0.08). Higher current CD4 count significantly favored a higher Cmin/population Cmin (0.04 per 100 cells, P = 0.05), as did self-reported antiretroviral side effects (0.25, P < 0.01).

Reference
1. la Porte C, Loutfy M, Walmsley S, et al. Antiretroviral pharmacokinetics in HIV-positive women with full virologic suppression on current regimens. 11th International Workshop on Clinical Pharmacology and HIV Therapy. April 7-9, 2010. Sorrento. Abstract 8.
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Offline red_Dragon888

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« Reply #92 on: April 08, 2010, 04:06:00 PM »
_______________________________________________



Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome - (04/03/10)


PLoS one, April 1 2010
 
"XMRV nucleic acid or proteins are found in 27% of prostate cancers and in 68% of chronic fatigue syndrome patients, and in less than 4-6% of normal controls, suggesting an association between the virus and human disease....The discovery of effective antiretroviral agents against XMRV would allow for rational design of clinical trials to prevent progression of prostate cancer or to treat CFS.....We report here for the first time that the integrase inhibitor, raltegravir (RAL), is extremely potent and selective against XMRV, when used at low submicromolar concentrations in both cell culture systems. Another IN inhibitor, L-000870812, and two NRTIs, ZDV and tenofovir disoproxil fumarate (TDF), also inhibit XMRV replication, but at higher concentrations. When combined, these compounds display synergistic effects, suggesting combined modalities to treat XMRV infection, thus delaying or preventing the selection of resistant viruses."
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« Reply #93 on: April 08, 2010, 04:06:55 PM »
Raltegravir, maraviroc, etravirine: an effective protease inhibitor and nucleoside reverse transcriptase inhibitor-sparing regimen for salvage therapy in HIV-infected patients with triple-class experience -


AIDS:
27 March 2010 - Volume 24 - Issue 6 - p 924-928
Research Letters


"Twenty-eight out of 106 (26.4%) co-screened patients harboured a R5-tropic virus and were thus enrolled in the study....All had been previously exposed to NRTIs, NNRTIs and at least three protease inhibitors, including lopinavir/ritonavir [28/28 (100%)], tipranavir/ritonavir [4/28 (14%)], and darunavir/ritonavir [10/28 (36%)]. Eleven (39%) patients had been previously treated with enfuvirtide......At week 48, all patients had an HIV-RNA load below 400 copies/ml (P < 0.0001) and 26/28 (93%) had less than 50 copies HIV-RNA/ml (P < 0.0001)......At week 48, the median increase in CD4+ cell count was 267 (136-355) cells/µl (Fig. 1b). The proportion of patients with CD4+ cell counts below 200 cells/µl was 36% (10/28) at baseline, and 7% (2/28) at week 48 (P = 0.0082)......In our study, the combination of raltegravir and maraviroc, and etravirine led to an unexpected rate of virological success, with a rapid and robust CD4+ cell recovery, despite a high pill burden regimen and potentially negative drug-drug interactions......we observed an improvement of lipid profile.In conclusion, our results suggest that a protease inhibitor and NRTI-sparing regimen of raltegravir and maraviroc, and etravirine is potent and well tolerated. Although long-term toxicity needs to be accurately evaluated, this regimen may represent a powerful option to regain full viral control and robust CD4+ cell recovery in patients with extensive drug resistance and R5-tropic HIV."
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #94 on: April 08, 2010, 04:07:49 PM »
Hepatitis C infection doubles kidney cancer risk
By ANI
April 8th, 2010


WASHINGTON - Infection with the hepatitis C virus increases the risk for developing kidney cancer, physicians at Henry Ford Hospital have found.


Using administrative data from more than 67,000 Henry Ford Health System patients, physicians found that over the period 1997-2008, 0.6 percent patients with hepatitis C infection developed kidney cancer whereas only 0.3 percent patients without the disease developed kidney cancer.


After controlling for age, gender, race and underlying kidney disease, hepatitis C infected patients had nearly double the risk of developing kidney cancer.


“These results add to growing literature that shows that the hepatitis C virus causes disease that extends beyond the liver, and in fact most of our HCV-infected kidney cancer patients had only minimal liver damage,” says Stuart C. Gordon, M.D., director of Hepatology at Henry Ford Hospital and lead author of the study.


The study was published in this month’s Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research. (ANI)
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #95 on: April 08, 2010, 04:13:41 PM »
Aging, Inflammation and the Immune System in HIV

(below are links to numerous studies and conference reports on inflammation & brain dysfunction, bone disease, cancers etc)

Jules Levin, NATAP

There have been publications in journals, lots of studies and discussion about inflammation, aging & chronic diseases in HIV-negatives for years, so this is NOT a new subject outside of HIV. It has been widely recognized that inflammation is associated with chronic viral diseases, HIV-negative individuals with chronic viral diseases have ongoing inflammation which  is associated with a dysregulated immune system. So observing this in HIV is no surprise and should have been expected although when these observatios started emerging in HIV at CROI, the annual HIV conference, several years ago it appeared to take the field by surprise and NO ONE was discussing this or paying much attention. At first large cohort studies in Europe and small studies in the USA reported premature onset of comorbidities, heart disease/cancers/bone disease/cognitive impairment/kidney function decline etc. At the same time I started reporting about these developments and in particular early onset of bone disease and osteopenia/otseoporosis in a significant percent of patients. Many researchers and officials gave me pushback that bone disease may not translate into increased fractures in HIV, and I had to laugh. Of course at this year's CROI several studies reported increased fracture rates in HIV and that HIV+ men face a unique concern regarding bone disease unlike among HIV-negative individuals where women present a more unique problem. And premature death was also found and associated with patients developing these comorbidities. Make no mistake about it, despite tremendous benefits to HAART an HIV-infected person still has a dysfunctional and weakened immune system, this is at the core of the aging and inflammation problems. Starting 2 years ago at CROI researchers started reporting in very small amounts of data that patients were experiencing premature aging reflected by onset of senescence and ongoing activation. Outside of HIV the elderly develop senescence, where the immune system becomes weakened and encourages onset of comorbidities. In HIV ongoing virus is present in some form in patients even with undetectable viral load, activation. All this contributes to inflammation. At the 2009 CROI there was quite a lot of new information that inflammation is associated with onset of heart disease, cognitive impairment. At this year's 2010 CROI there was an explosion of studies on aging and inflammation; studies finding patients are experiencing ongoing inflammation and it's associated with HCV, heart disease, kidney function, brain disease. At CROI there were several studies reporting that ART intensification with the CCR5 drug maraviroc or the integrase raltegravir appeared to reduce activation & perhaps inflammation. So now this has become I think the most important area in HIV. The issue of aging and inflammation are getting traction among academic researchers, drug companies and at the NIH and the Division of AIDS within the NIH. But a lot more research is needed as we have just begin to scrtach the surface in trying to understand the problem and if we can intervene to prevent or ameliorate the problem. Of special note is, what causes inflammation, because inflammation merely reflects a problem below the surface. There is quite a bit of research suggestion the most significant problems might be senescence and ongoin activation, causing inflammation. There appear to be many other potential contributing factors including mitochondrial toxicity, a patient history of substance abuse poor lifestyle behaviors, ARTs, and perhaps others. SO, we need a very focused targeted and dedicated effort by the NIH to address these questions. We need funding dedicated by the NIH to aging & HIV and we need support from the broad community to influence the NIH to do this.


Inflammation, Aging & Brain Dysfunction

Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function - (04/03/10)
NEUROLOGY March 2010;
"we found higher hs-CRP values to be associated with worse performance in executive functions, including tests of psychomotor speed and attention. Other cognitive domains, i.e., memory and linguistic skills, showed no association with CRP".....Serum hs-CRP levels were higher in subjects with a history of hypertension....Higher high-density lipoprotein levels were associated with lower hs-CRP ....."The phenomenon of cognitive aging is characterized by deficits in executive functions, information processing speed, and attention. Histopathologic studies showed an age-related decrease of myelin and the number of myelinated fibers.31 In vivo, DTI appears to be the most sensitive imaging measure"....."Recent interventional studies using antiinflammatory drugs such as aspirin and statins to lower circulating CRP levels showed a significant reduction in the incidence of cardiovascular events.36,37 There is also evidence of a beneficial effect of lifestyle interventions on cognitive functions, such as physical activity and body weight control,38,39 which have been shown to decrease circulating CRP levels.38,39 Whether lowering of CRP can also prevent cognitive decline and/or microstructural white matter alterations needs to be addressed in upcoming clinical trials."


Inflammation, CRP & new test (DTI, difussion tensor imaging) - Are white matter signal abnormalities clinically relevant? Editorial - (04/03/10)



CROI Selected Highlights- Bone, Cancer, Inflammation, Low-level HIV, HCV coinfection, neurologic, cardiovascular disease, renal


here is link to full NATAP CROI coverage of 160 reports:
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #96 on: April 08, 2010, 04:15:08 PM »
Subjective Memory Loss Predicts Dementia
By Charles Bankhead, Staff Writer, MedPage Today
Published: April 06, 2010


Subjective memory impairment predicted conversion to dementia or Alzheimer's disease as early as three years before diagnosis, according to a German study.

Subjective memory impairment, plus worry about the impairment, more than tripled the likelihood of conversion to any dementia or Alzheimer's disease at follow-up 18 months and three years later, Frank Jessen, MD, of the University of Bonn, and colleagues wrote in the April Archives of General Psychiatry.

Patients with subjective memory impairment at baseline and mild cognitive impairment 18 months later had almost 10 times the risk of any dementia at three years, and almost 20 times the risk of Alzheimer's disease, compared to patients without subjective memory impairment at baseline or mild cognitive impairment at the first follow-up.


Action Points 
--------------------------------------------------------------------------------

Explain to patients that subjective memory impairment was associated with conversion to dementia, particularly dementia in Alzheimer's disease.



Study participants who had subjective memory impairment at baseline and mild cognitive impairment at the first follow-up visit had the highest risk of developing dementia.

"Our data suggest that beyond factors affecting one's own experience of memory decline . . . , subjective memory impairment may reflect initial impairment specifically related to the clinical manifestations of Alzheimer's disease," the researchers wrote.


"Because subjects with impairment on baseline testing were excluded in this study, our data support the concept of subjective memory impairment as a pre-mild cognitive impairment condition in Alzheimer's disease."


"The prediction of dementia in Alzheimer's disease by subjective memory impairment with subsequent amnestic mild cognitive impairment supports the model of a consecutive, three-stage clinical manifestation of Alzheimer's disease from subjective memory impairment via mild cognitive impairment to dementia," they concluded.


The anticipated development of disease-modifying treatment for Alzheimer's disease has fueled research into identification of at-risk and prodromal syndromes for dementia.


The research has already led to identification of mild cognitive impairment as an at-risk condition associated with an annual conversion rate for dementia of 10% to 20%, the authors wrote.


Mild cognitive impairment reflects neuropsychological test performance that falls below age-, sex-, and education-adjusted norms. However, studies have shown that Alzheimer's disease-related brain pathology begins to evolve several years before the onset of mild cognitive impairment.


"Recently, the temporal association of this pre-mild cognitive impairment cognitive decline with the occurrence of cognitive complaints in subjects with subjective dementia has been demonstrated, suggesting that initial worsening of cognitive performance is already experienced by affected individuals," the authors wrote.


"This may qualify subjective memory impairment as a clinical indicator of pre-mild cognitive impairment cognitive decline."


To examine the association between subjective memory impairment and dementia, investigators analyzed data from an ongoing cohort study.


They identified study participants 75 or older who did not have dementia in the clinical judgment of their primary care physicians. All participants had reported at least one visit with their primary care physicians within the past 12 months. Nursing-home residents, patients who had only at-home visits with physicians, and deaf or blind patients were excluded.


The baseline sample comprised 3,327 study participants. Of those, 2,820 participated in an at-home follow-up at 18 months, and 2,487 participated in the three-year, at-home follow-up.


The follow-up visits included interviews by trained psychologists and a battery of neuropsychologic tests. At the 18-month follow-up, participants were asked: Do you feel like your memory is becoming worse? Participants had three possible answers:
No
Yes, but this does not worry me
Yes, this worries me
Mild cognitive impairment and dementia were defined according to accepted diagnostic criteria.
Of 2,415 participants included in the analysis, 1,027 had no subjective memory impairment at baseline, while 1,006 had subjective memory impairment without worry, and 382 had subjective memory impairment with worry.


Investigators found 110 cases of conversion to any type of dementia at the first or second follow-up visit, 54 cases of conversion to dementia in Alzheimer's disease, and 26 cases of vascular dementia.
Among patients without subjective memory impairment at baseline, 26 had conversion to any dementia and nine each had conversion to dementia in Alzheimer's disease and vascular dementia.


Study participants without subjective memory impairment at baseline or mild cognitive impairment at the first follow-up served as the reference group.


As compared with the reference group, subjective memory impairment without worry almost doubled the likelihood of conversion to any dementia (HR 1.83, 95% CI 1.12 to 2.99) and tripled the risk of conversion to dementia in Alzheimer's disease (HR 3.04, 95% CI 1.36 to 6.81).


Subjective memory impairment with worry was associated with a hazard ratio of 3.53 for conversion to any dementia (95% CI 2.07 to 6.03) and a hazard ratio of 6.54 for conversion to dementia in Alzheimer's disease (95% CI 2.82 to 15.20).


Participants with mild cognitive impairment had even higher rates of dementia conversion. As compared with the reference group, participants with no subjective memory impairment at baseline and mild cognitive impairment at the first follow-up visit had a four-fold increased risk of conversion to any dementia at the second follow-up visit (HR 4.41, 95% CI 1.44 to 13.48) and almost a six-fold greater risk of conversion to dementia in Alzheimer's disease (HR 5.74, 95% CI 1.09 to 30.16).


Participants with subjective memory impairment at baseline and mild cognitive impairment at the first follow-up visit had the greatest risk of dementia conversion at the second follow-up visit: A nine-fold increased hazard for any dementia (HR 8.92, 95% CI 3.69 to 21.60) and a 19-fold increased hazard for conversion to dementia in Alzheimer's disease (HR 19.33, 95% CI 5.29 to 70.81).


The presence of amnestic mild cognitive impairment further increased the likelihood of dementia conversion.


Neither subjective memory impairment nor mild cognitive impairment was associated with vascular dementia.


Limitations of the study, according to the authors, included small numbers in some subgroups due to definitions used, use of a scoring system that did not allow in-depth testing, and self-report of subjective memory impairment, which was therefore not assessed in detail.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #97 on: April 09, 2010, 01:46:16 PM »
Influence of Adherent and Effective Antiretroviral Therapy Use on Human Papillomavirus Infection and Squamous Intraepithelial Lesions in Human Immunodeficiency Virus–Positive Women




The Journal of Infectious Diseases March 1 2010;201:681–690



"In summary, we found that effective and adherent HAART use was significantly associated with a reduced burden of HPV infection and SILs among HIV‐positive women. These protective effects may help explain why age‐specific cervical cancer rates have not increased despite the greater survival of HIV‐positive women during the HAART era. However, the overall public health burden of cervical cancer in HIV‐positive patients could grow as this population increasingly enters older age groups, which have higher cervical cancer rates......The average prevalence of oncogenic HPV infection decreased 36% in adherent women (from 22% before to 14% after HAART initiation) and 12% in nonadherent individuals (from 24% before to 21% after HAART initiation)....adherent women had a highly significant reduction in oncogenic HPV prevalence following their initiation of HAART (odds ratio [OR] [after vs before], 0.60 [95% confidence interval {CI}, 0.44–0.81];  p=.001), whereas nonadherent HAART use was not significantly associated with a change in oncogenic HPV prevalence (Table 2). A direct comparison of rates in adherent women versus nonadherent women after HAART initiation suggested an about 30% reduction in oncogenic HPV prevalence related to adherence (OR [adherent vs nonadherent], 0.70 [95% CI, 0.48–1.01];  p=.06)......Adherent HAART use was also associated with a reduction in the incident detection rate of oncogenic HPV infection. Specifically, the rate of incident detection decreased 33%......Our major end point was oncogenic HPV–positive SILs (oncHPV+ SILs), lesions that are thought to have the potential to result in tumors. Adherent users had a significant reduction in oncHPV+ SIL prevalence after HAART initiation.....there was a significant relationship between adherent HAART use and the rate of oncHPV+ SIL clearance...which was significantly greater than the oncHPV+ SIL clearance rate observed among nonadherent women.....The average prevalence of oncogenic HPV infection decreased 20% in patients using effective HAART, from 20% before to 14% after HAART initiation, and did not decrease but actually increased slightly in those using ineffective HAART, from 22% before to 24% after HAART initiation."



Howard Minkoff,1 Ye Zhong,2 Robert D. Burk,2 Joel M. Palefsky,4 Xiaonan Xue,2 D. Heather Watts,6 Alexandra M. Levine,5 Rodney L. Wright,3 Christine Colie,8 Gypsyamber D’Souza,7 L. Stewart Massad,9 and Howard D. Strickler2

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #98 on: April 09, 2010, 01:47:20 PM »
"The results of this study suggest that it is common for anal and cervical HPV infections to occur consecutively. The high degree of genotype‐specific concordance indicates a common source of infection, such as vaginal and anal intercourse with the same infected partner(s), although alternate routes of transmission, including nonpenetrative sexual contact and autoinoculation, need to be explored. The clinical consequences of our observations include higher rates of genital warts and anal and cervical cancers among HPV‐infected women, through the spread of infection within the anogenital area, although cytologic information was not included in this analysis. These results provide at least a partial basis for the finding that women with cervical intraepithelial neoplasia or cancer are at higher risk of anal cancer. Although anal cytologic screening is cost‐effective in HIV‐infected men who have sex with men [30], studies of the efficacy of this approach in other HR groups have not been conducted."



Sequential Acquisition of Human Papillomavirus (HPV) Infection of the Anus and Cervix: The Hawaii HPV Cohort Study.



The Journal of Infectious Diseases May 1 2010;201:1331–1339


Marc T. Goodman,1 Yurii B. Shvetsov,1 Katharine McDuffie,1 Lynne R. Wilkens,1 Xuemei Zhu,1 Pamela J. Thompson,1 Lily Ning,2 Jeffrey Killeen,3 Lori Kamemoto,3 and Brenda Y. Hernandez1
1Epidemiology Program, Cancer Research Center of Hawaii, and 2University Health Services, University of Hawaii, and 3Kapiolani Medical Center for Women and Children, Honolulu, Hawaii



ABSTRACT


Background. Relatively little is known about the epidemiology of anal human papillomavirus (HPV) infection in healthy women and its association with cervical HPV infection.

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #99 on: April 09, 2010, 01:48:09 PM »
More Than Half in Barcelona HIV Clinic Use Alternative Therapies

11th International Workshop on Clinical Pharmacology and HIV Therapy, April 7-9, 2010, Sorrento

Mark Mascolini

More than half of 1000 HIV-infected people surveyed at a large HIV clinic in Barcelona use complementary or alternative therapies that they believe help them control their infection or its symptoms [1]. Better educated people were more than twice as likely to use an alternative therapy, and only half who used such remedies asked their HIV physicians about them. Many of the agents used have some impact on the CYP3A4 enzyme, which is involved in the metabolism of many key antiretrovirals.

Jose Molto and colleagues at the University Hospital Germans Trias i Pujol gave a self-administered questionnaire to 1000 HIV-infected adults attending the HIV clinic pharmacy department. The researchers matched results with medical records from the clinic.

The group's age averaged 43.2 years (+/- 8.5 standard deviation), 75.4% were men, 88% were Caucasian, and 73.7% had a high school or college education. But only 57.4% had a job, and 49.7% had an income below 1000 Euros per month. The study group averaged 12.6 years (+/- 7.5) since their HIV diagnosis, 43.1% were gay men, 88.7% were taking antiretrovirals, 79.9% had a viral load below 50 copies, and 60.7% had non-HIV symptoms. The group's CD4 count averaged 572 (+/- 314).

Of the 1000 survey respondents, 584 acknowledged using some alternative therapy, and most used more than one: the median number of unlicensed remedies was 3 (interquartile range 2 to 7). Of the 584 people using alternative remedies, only 324 (55.5%) had discussed their use with their HIV clinician, and only 124 (21.2%) had been monitored for potential interactions between such agents and antiretrovirals.

More than 400 people used dietary supplements, and more than 300 used herbal remedies. The most frequently used agents that may interfere with antiretroviral metabolism were garlic (71 people, CYP3A4 induction), ginseng (67 people, CYP3A4 inhibition), Echinacea species (60 people, CYP3A4 induction and/or inhibition), and milk thistle (36 people, CYP3A4 induction).

Five factors independently raised the chance of using alternative therapies:

·      Consultation with primary care physician about possibility of using alternative therapies: odds ratio (OR) 3.12, 95% confidence interval (CI) 2.30 to 4.23, P < 0.001

·      High school or university degree: OR 2.63, 95% CI 1.78 to 3.88, P < 0.001

·      Non-HIV-related symptoms: OR 1.68, 95% CI 1.24 to 2.28, P = 0.001

·      Perception that alternative therapies are totally or partially beneficial: OR 2.28, 95% CI 1.18 to 4.41, P = 0.015

·      Non-Caucasian race: OR 1.65, 95% CI 1.07 to 2.56, P = 0.024

Molto and coworkers recommended that HIV patients and physicians "should be sensitized to the potential risks . . . of complementary or alternative medicine, and especially herbal remedies, and encouraged to discuss such therapies openly during clinical visits."

Reference
1.  Molto J, Miranda C, Malo S, et al. Patterns and correlates of the use of complementary and alternative medicine among HIV-infected patients. 11th International Workshop on Clinical Pharmacology and HIV Therapy. April 7-9, 2010. Sorrento. Abstract 31.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #100 on: April 09, 2010, 01:48:53 PM »
Researchers discover a new way HIV infects women: inflammatory response causes infection



"The mechanism of this breakdown appears to be due to inflammatory factors produced by epithelial cells themselves, in response to HIV-1 exposure, that destroy the tight junctions between epithelial cells, thereby allowing microbes access to the inside of the body......The crossing of the bacteria by similar mechanism can lead to chronic inflammation and activation of immune cells of the body."


"In conclusion, the current study provides evidence for the first time that HIV-1 exposure at the mucosal surface leads to direct response by the mucosal epithelium, seen by production of inflammatory cytokines. This response is rapid, independent of viral infection and likely plays a key role in initiation of mucosal damage. This information will be critical for strategies to target control of mucosal damage......We further determined that exposure of the epithelial monolayers to HIV-1 led to enhanced production of a number of inflammatory cytokines, including TNF-α, by both intestinal and genital epithelial cells. When epithelial cells were exposed to HIV-1 in presence of anti-TNF antibody, there was no significant decrease in TER, indicating that TNF played a major role in impairing the barrier functions.....we found evidence for small but significant bacterial and viral translocation across epithelial monolayers following HIV-1 exposure......A recent study showed impairment of barrier function in intestinal biopsies of HAART-naïve patients compared to those on HAART treatment [14]. Increased production of cytokines IL-2, IL-4, IL-5 and TNF-α was found in supernatants of cultured intestinal biopsies in this study. Their conclusion was that following infection, HIV replication in target cells leads to local increase of inflammatory cytokines in the intestinal mucosa, which induce barrier impairment. This supports previous studies where PBMCs co-cultured with HIV-infected macrophages resulted in increased production of a number of cytokines, including TNF-α, IL-1β, IFN-α and IFN-γ which were shown to compromise epithelial barrier function [34]. The prevailing opinion from these studies is that the effect on epithelial barrier is likely mediated via immune cell activation due to viral replication"

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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« Reply #101 on: April 16, 2010, 02:05:14 PM »
EDITORIAL COMMENTARY

HIV Drug Resistance over the Long Haul




Clinical Infectious Diseases May 1 2010



P. Richard Harrigan




BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada




      (See the article by The UK Collaborative Group on HIV Drug Resistance and UK CHIC Study Group, on pages 1275–1285.)










In this issue, The UK Collaborative Group on HIV Drug Resistance and UK CHIC Study Group present data from a large, long‐term study of human immunodeficiency virus (HIV) drug resistance [1]. Their data are derived from a clinic‐based collaborative study (the UK Collaborative Group on HIV Drug Resistance), which includes data from >50,000 routinely performed HIV drug resistance tests in the United Kingdom. The collaborative nature of the study group allowed them to examine resistance in almost 8000 individuals for periods of up to 8 years and to gain insight into the determinants of drug resistance in a “real world” setting.




Large longitudinal cohort studies such as this are an important complement to randomized clinical trials, particularly for monitoring drug resistance. As the authors point out, clinical trials of antiretrovirals tend to be relatively short and relatively small. They may also tend to include individuals who are more likely than average to be adherent to treatment. Most importantly, these randomized trials also typically monitor patients only until their initial treatment regimen fails, at which point they may drop out of the study, and no further analyses of resistance are performed.




Cohort studies such as this are one of the few ways to monitor the long‐term risk of developing HIV drug resistance. The authors find that the risk of developing a resistant genotype is <20% over 8 years for patients starting “modern” HIV treatment regimens. Given the number of antiretrovirals which are now available, this can only be considered to be good news for patients starting treatment. Other main conclusions of the study are that the risk of detecting mutations conferring resistance to the protease inhibitor class of therapy in those who started highly active antiretroviral therapy (HAART) regimens which included a modern ritonavir‐boosted protease inhibitor regimen was about one‐third of the risk of detecting nonnucleoside reverse‐transcriptase inhibitor resistance. Because there was no difference in the risk of nucleoside reverse‐transcriptase inhibitor resistance, the implication of the study is that those who started nonnucleoside reverse‐transcriptase inhibitor–based HAART were much more likely to have 2‐class HIV drug resistance than those who started therapy with boosted protease inhibitors. This conclusion is consistent with data from clinical trials and with studies by our own group in British Columbia and others.




There are a number of caveats which should be kept in mind when interpreting the data, many of which are addressed in detail in the Discussion section [1]. First, there have been temporal changes in the use of HIV drug resistance testing and in the nucleoside analogue pairs available over the long course of the study (see Table 1 [1]). The authors adjust their analysis for calendar year, but subtle confounding may remain. For example, it was simply impossible to obtain tenofovir‐emtracitabine during the first years of the study, but it appears to be one of the most common combinations later in the study. In addition, the observational nature of the study could result in potential contributions of sampling bias—some predictors of resistance may arise from being associated with being tested. The risk of developing resistance may not be simply disentangled from the calendar year of drug availability, the probability of undergoing resistance testing, or variable adherence to medications. It is also important to note that many patients changed their therapies over the course of the study as a normal part of routine clinical management. The main comparisons were made according to the type of regimen that individuals initially started regardless of subsequent drug switches of any part of their regimen.




Finally, many patients no longer initiate HAART with the nucleoside analogue pairs described in this study; thus, the estimates of drug resistance provided for those with the longest follow‐up may not accurately mirror those who start antiretroviral therapy in 2010. This statement is not a criticism of the study but merely reflects the fact that it is impossible to have both long term follow‐up and today’s most clinically relevant therapies in an area that changes as rapidly as HIV treatment. Overall, the study provides an important description of “where we are now.” The analysis provided is of the usual high quality of this group.



Acknowledgments




Financial support.CIHR/GSK Research Cair in Clinical Virology.




Potential conflicts of interest.P.R.H. has received grants from, served as an ad hoc advisor to, or spoken at various events of Pfizer, GlaxoSmithKline, Abbott, Merck, Virco, and Monogram.

Reference




    * 1.The UK Collaborative Group on HIV Drug Resistance and UK CHIC Study Group. Long‐term probability of detecting drug‐resistant HIV in treatment‐naive patients initiating combination antiretroviral therapy. Clin Infect Dis 2010;50(9):1275–1285 (in this issue).
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline georgep77

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Re: http://natap.org/
« Reply #102 on: April 16, 2010, 03:42:09 PM »
Thanks for the news Dragon   :)
Come on Sangamo,  Geovax,  Bionor immuno, ...Make us happy !!!
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #103 on: April 17, 2010, 01:32:21 PM »
"We have shown that the biochemical profile of G1 CHC patients is characterized by lower-than-normal serum 25(OH)D levels, and that a low 25(OH)D level is independently related to severe fibrosis and a low likelihood of SVR after standard-of-care antiviral therapy.....Our study shows that low 25(OH)D levels are independently associated with female sex and with severity of necroinflammatory activity....This study also offers the first evidence that low 25(OH)D serum levels, together with known risk factors for fibrosis severity, such as older age, low cholesterol levels, and high necroinflammatory activity,[26] are independently associated with the presence of severe fibrosis......It is conceivable that a reduced 25(OH)D level might by itself favor progression of fibrosis. Different experimental models showed that vitamin D, via interaction with vitamin D receptor, protects against oxidative stress production,[29] can influence the migration, proliferation, and gene expression of fibroblasts,[30][31] and reduces the inflammatory and fibrogenic activity of liver stellate cells.....However further prospective cohort studies will be needed to determine the causal association between vitamin D deficiency and fibrosis in patients with CHC....Another interesting finding of this study is the evidence that lower 25(OH)D serum levels were an independent negative risk factor for SVR....this observation will require further validation in different, large cohorts of patients, but is supported by experimental data that suggest a role of vitamin D in the modulation of the immune response,[32][33] and by recent clinical data[36] reporting higher early virological response rate in CHC treated with standard of care plus vitamin D, compared with those treated with standard of care only"



Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C



Hepatology April 2010


Salvatore Petta 1 2 *, Calogero Cammà 1 3, Concetta Scazzone 4, Claudio Tripodo 5, Vito Di Marco 1, Antonino Bono 4, Daniela Cabibi 5, Giusalba Licata 1, Rossana Porcasi 5, Giulio Marchesini 6, Antonio Craxí 1

1Cattedra ed Unità Operativa di Gastroenterologia, DiBiMIS, University of Palermo, Italy

2Dipartimento di Biopatologia e Metodologie Biomediche, University of Palermo, Italy

3IBIM Consiglio Nazionale delle Ricerche, Palermo, Italy

4Dipartimento di Biotecnologie Mediche e Medicina Legale Sezione Chimica e Biochimica Medica, University of Palermo, Italy

5Cattedra di Anatomia Patologica, University of Palermo, Italy

6Dipartimento di Medicina e Gastroenterologia, Alma Mater Studiorum, University of Bologna, Italy

email: Salvatore Petta (petsa@inwind.it)




*Correspondence to Salvatore Petta, Gastroenterologia & Epatologia, Piazza delle Cliniche, 2, 90127 Palermo, Italy







Abstract




25-Hydroxyvitamin D (25[OH]D) can potentially interfere with inflammatory response and fibrogenesis. Its role in disease progression in chronic hepatitis C (CHC) and its relation with histological and sustained virological response (SVR) to therapy are unknown. One hundred ninety-seven patients with biopsy-proven genotype 1 (G1) CHC and 49 healthy subjects matched by age and sex were consecutively evaluated. One hundred sixty-seven patients underwent antiviral therapy with pegylated interferon plus ribavirin. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. Tissue expression of cytochrome (CY) P27A1 and CYP2R1, liver 25-hydroxylating enzymes, were assessed by immunochemistry in 34 patients with CHC, and in eight controls.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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« Reply #104 on: April 17, 2010, 01:33:08 PM »
Drug shared by addicts seems to protect against HIV brain dementia
Could heroin hold the clues for a new protective agent?
Washington, DC – To their surprise, researchers at Georgetown University Medical Center (GUMC) have discovered that morphine (a derivate of the opium poppy that is similar to heroin) protects rat neurons against HIV toxicity - a finding they say might help in the design of new neuroprotective therapies for patients with the infection.


The discovery, being presented at the annual meeting of the Society of NeuroImmune Pharmacology, also helps explain why a subset of people who are heroin abusers and become infected with HIV through needle sharing don't develop HIV brain dementia. This brain disorder includes cognitive and motor abnormalities, anxiety and depression.


"We believe that morphine may be neuroprotective in a subset of people infected with HIV," says the study's lead investigator, Italo Mocchetti, PhD, Professor of neuroscience at GUMC.


"That is not to say that people should use heroin to protect themselves – that makes no medical sense at all – but our findings gives us ideas about designing drugs that could be of benefit.


"Needless to say we were very surprised at the findings," he added. "We started with the opposite hypothesis – that heroin was going to destroy neurons in the brain and lead to HIV dementia."


The researchers conducted the study because they knew that a number of HIV-positive people are also heroin abusers, and because of that, some are at high risk of developing neurological complications from the infection. Others, however, never develop these cognitive problems, Mocchetti says.


Because little is known about the molecular mechanisms linking opiates and HIV neurotoxicity, Mocchetti and his team conducted experiments in rats. They found that in the brain, morphine inhibited the toxic property of the HIV protein gp120 that mediates the infection of immune cells. With further investigation, they concluded that morphine induces production of the protein CCL5, which they discovered is released by astrocytes, a type of brain cell. CCL5 is known to activate factors that suppress HIV infection of human immune cells. "It is known to be important in blood, but we didn't know it is secreted in the brain," says Mocchetti. "Our hypothesis is that it is in the brain to prevent neurons from dying."


They say morphine blocked HIV from binding to CCR5 receptors it typically uses to enter and infect cells. The researchers believe CCL5 itself attached to those receptors, preventing the virus from using it. In this way, it prevented HIV-associated dementia. This effect, however, only worked in the M-trophic strain of HIV, the strain that most people are first infected with. It did not work with the second T-trophic strain that often infects patients later.


"Ideally we can use this information to develop a morphine-like compound that does not have the typical dependency and tolerance issues that morphine has," says Mocchetti.

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #105 on: April 17, 2010, 01:34:29 PM »
FDA Updates Product Labeling for Sustiva (Efavirenz)

The Food and Drug Administration recently approved revisions to the package insert for Sustiva (efavirenz), a non-nucleoside reverse transcriptase inhibitor, for both capsules and tablets…


As of July 2009, the Antiretroviral Pregnancy Registry has received prospective reports of 661 pregnancies exposed to efavirenz-containing regimens, nearly all of which were first trimester exposures (606 pregnancies). Birth defects occurred in 14 of 501 live births (first trimester exposure) and 2 of 55 live births (second/third-trimester exposure). …


Monitoring of liver enzymes before and during treatment is recommended for patients with underlying hepatic disease, including hepatitis B or C infection; patients with marked transaminase elevations; and patients treated with other medications associated with liver toxicity. … Liver enzyme monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors. …


Posaconazole: Avoid concomitant use unless the benefit outweighs the risks[.]


Maraviroc: Refer to the full prescribing information for maraviroc for guidance on coadministration with efavirenz. …


Because of the extensive cytochrome P450-mediated metabolism of efavirenz and limited clinical experience in patients with hepatic impairment, caution should be exercised in administering Sustiva to these patients …


Some patients taking Sustiva have experienced serious liver problems including liver failure resulting in transplantation or death. Most of these serious side effects occurred in patients with a chronic liver disease such as hepatitis infection, but there have also been a few reports in patients without any existing liver disease.


The complete revised label is available at the FDA Web site.

More information is available:
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #106 on: April 17, 2010, 01:35:22 PM »
Pharmacokinetic-pharmacodynamic (PK-PD) analyses of TMC435 in treatment-naïve hepatitis C (HCV)-infected patients in the OPERA-1 study - see attached full poster report

 

Reported by Jules Levin, EASL Apr 14-18 2010 Vienna Austria

V. Sekar1, P. Vis2, O. Lenz2, P. Meyvisch2, M. Peeters2, G. De Smedt2 1Tibotec Inc, USA; 2Tibotec BVBA, Belgium

 

AUTHOR CONCLUSIONS

- In treatment-naive HCV-infected patients, following 28 days of treatment with TMC435 in combination with P/R, a dose-proportional increase in TMC435 exposure was observed from 25 to 75mg QD, with a more than dose-proportional increase in TMC435 exposure observed from 75 to 200mg QD.

- There was no clear PK-PD relationship between TMC435 exposure and antiviral activity with TMC435 doses of 75mg QD or higher.

- A trend towards mild increases in serum bilirubin and ALP was observed with higher TMC435 exposure, with increases mainly observed at the 200mg dose.

- However, no clear PK-PD relationship was observed for other liver parameters.

- The PK-PD findings reported here support the TMC435 75 and 150mg QD doses selected for further evaluation in treatment-naive patients as part of the ongoing Phase IIb trial, PILLAR.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #107 on: April 21, 2010, 03:33:26 PM »
Added Sugar Adds Up to Heart Risk



MedPage Today

Published: April 20, 2010



On average, Americans get nearly 16% of their total dietary calories from sugars added to processed foods during manufacturing, researchers found.




And a high intake of such sugars -- mainly sucrose from beets and cane and high fructose corn syrup -- is correlated with some key measures of dyslipidemia, according to Miriam Vos, MD, of Emory University in Atlanta, and colleagues.




Because dyslipidemia is a risk factor for cardiovascular disease, the findings support dietary guidelines aimed at reducing consumption of added sugars, Vos and colleagues said in the April 21 issue of the Journal of the American Medical Association.




The findings are not a surprise, according to Rachel Johnson, PhD, of the University of Vermont in Burlington. Johnson, a nutritionist, was the primary author of a statement on added sugars issued in August 2009 by the American Heart Association. (See Cut Back on Added Sugar, AHA Recommends)

Action Points 
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #108 on: April 21, 2010, 03:33:57 PM »
Gilead stops hepatitis drug test after ‘adverse events’
Tuesday, April 20, 2010


Citing “significant laboratory abnormalities and adverse events” in patients, Gilead Sciences stopped a clinical test of a hepatitis C drug.


The Foster City company (NASDAQ: GILD) will review data from this Phase II test of GS 9450, a caspase inhibitor. The company has been studying it for treatment of hepatitis C and also for nonalcoholic steatohepatitis.


Gilead licensed the drug from LG Life Sciences Inc. in 2007, paying $20 million upfront for the rights to the drug except in Korea, China and India. The company also agreed to pay for a collaborative research program and to pay milestones of up to $182 million if the drug did well in development.


“Patient safety is Gilead’s top priority,” the business said in a press release.


Gilead didn’t describe the problems in detail.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #109 on: April 21, 2010, 03:35:22 PM »
Researchers discover a new way HIV infects women

http://www.labspaces.net/103040/Researchers_discover_a_new_way_HIV_infects_women

Friday, April 9, 2010

Women are susceptible to HIV, the virus that causes AIDS, but scientists have been puzzled as to how it finds its way into the female reproductive tract.

One theory has been that trauma, such as a little tear during intercourse, causes HIV to cross epithelial cells – the protective barrier that keeps out infection. There is also the suggestion an unknown mechanism is at work.

For the first time, researchers at McMaster University have discovered the culprit could be HIV itself and what the virus does when it binds to epithelial cells.

"What it does is that it makes the electrical barrier resistance of epithelial cells decrease. By doing that, the virus can cross the barrier," said lead researcher Charu Kaushic, associate professor in the Centre for Gene Therapeutics and the department of pathology and molecular medicine in the Michael G. DeGroote School of Medicine. She is also a researcher with the Michael G. DeGroote Institute of Infectious Disease Research.

"This is a significant step forward in defining where prevention strategies, such as microbicides and vaccine, need to focus. Instead of trying to stop HIV from infecting the target cells underneath the epithelium, we need to think about ways to stop the virus from attaching to epithelial cells themselves."

The study, which appears in the journal PLoS Pathogens, shows HIV can break down the mucosal barrier in the intestinal and female genital tract, allowing the virus to cross during intercourse.

The breakdown appears to be due to inflammatory factors produced by epithelial cells themselves, in response to HIV. This destroys the tight junctions between epithelial cells and gives HIV and other microbes access to inside the body, the researchers said.

Worldwide, half of the 40 million people infected with HIV are women. Among heterosexuals, women are the fastest growing group to be infected.

Scientists have been faced with the question of how HIV actually gets underneath epithelial cells to infect other cells that are susceptible to HIV. "It's not the cells on top," Kaushic said. "It is the immune cells underneath that have all the receptors that HIV likes to latch on to and that allow the virus to replicate and establish infection. But it has to cross the epithelial barrier first!"

The McMaster researchers grew purified primary epithelial cells in the laboratory from small pieces of tissues that were removed from women's uterus during hysterectomies, with their consent. Then, they began to study how HIV actually interacts with these cells. The electrical resistance in these cultures is used to monitor how well the epithelial cell cultures are growing and functioning.

Aisha Nazli, a researcher in Kaushic's laboratory, noticed every time she put HIV on epithelial cells their resistance went down significantly. Repeated tests confirmed this.

Kaushic said the surface protein of the virus causes the epithelial barrier to break. "The surface protein signals to the inside of the epithelial cells by binding to it", she said. "The epithelial cells start making inflammatory proteins which cause these cells to go on their self-destructive pathway."

Kaushic's lab conducted the research in collaboration with researchers in the department of molecular genetics at the University of Toronto and the department of medical biology at Laval University. She holds a New Investigator Award in HIV from the Canadian Institutes of Health Research (CIHR) and an Early Researcher's Award from the Ontario government.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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« Reply #110 on: April 22, 2010, 03:26:37 PM »
Health Department Highlights Health Risks of Unprotected Anal Sex among Heterosexual Women in New York City--New survey suggests that women are less likely than men to use protection during anal intercourse

'People engaging in anal sex should always use condoms'
"women are less likely than men who have sex with men to use condoms during anal sex. The figure is just 23%, according to the new report, compared to 61% among men who have sex with other men."Only 11% of the highest-risk women (versus 47% of those using condoms) said a provider had recommended testing in the past year – even though 94% of them had seen one"


April 21, 2010 – Unprotected anal sex poses well known health hazards for men, but new research suggests that the practice is a significant health issue for women as well. More than 100,000 New York City women engage in anal intercourse each year, according to a new report from the Health Department, and many are not taking the steps needed to prevent HIV and other sexually transmitted infections.


Anal membranes are easily damaged during sex, facilitating the spread of infection. Past studies suggest that anal exposure to HIV poses 30 times more risk than vaginal exposure. But the New York City findings suggest that women are less likely than men who have sex with men to use condoms during anal sex. The figure is just 23%, according to the new report, compared to 61% among men who have sex with other men. The full report is available at nyc.gov/health.


“Tens of thousands of New Yorkers are engaging in sexual behavior that is especially risky,” said Dr. Thomas Farley, New York City Health Commissioner. “Many people are aware of the risk of HIV when men have sex with other men, but this report shows that a large number of women also are putting themselves at high risk through unprotected anal sex. For both men and women, the overall message is clear: Never engage in unprotected anal sex. Use a condom every time.”


Just as condoms are especially important for people who engage in anal intercourse, so is HIV testing. Yet the new report finds that women who engage in unprotected anal sex have lower testing rates than women who always use condoms during anal sex – 35% versus 63%, respectively. By the same token, women who had unprotected anal sex were the least likely to report that a health care provider had offered HIV testing during the past year. Only 11% of the highest-risk women (versus 47% of those using condoms) said a provider had recommended testing in the past year – even though 94% of them had seen one.


The report does not estimate the HIV burden among women who engage in unprotected anal sex, but most HIV infections diagnosed in women result from heterosexual intercourse. Among women with known sources of exposure, heterosexual contact accounted for 90% of the infections diagnosed in New York City in 2008.
Unprotected anal sex is most common among younger women and those with multiple partners
Women 18 to 24 years old are nearly six times more likely than those aged 45 to 64 to report unprotected anal sex (11% versus 2%). And whereas 15% of women with three or more sex partners reported engaging in anal sex in the past year, the figure was just 4% among those with one partner. Reports of anal sex in the past year are similar across race and ethnicity, with Asian women reporting 8%, white women 7%, Hispanic women 6% and black women 4%.
Recommendations for reducing sexually transmitted infections
The new report highlights the importance of safer sex in a city where approximately 74,000 new sexually transmitted infections are reported each year, along with 3,800 new HIV diagnoses. Some recommendations:
Health care providers should offer STI and HIV testing to all patients, regardless of their stated sexual history.
People engaging in anal sex should always use condoms. Free NYC Condoms and other alternative male condoms, in addition to female condoms and lubricant, are available at locations throughout New York City. Call 311 or visit nyc.gov/condoms for more information.
Unless they’re in mutually monogamous relationships, people who have had unprotected sex should get tested for HIV and other STIs at least once a year. Free, confidential screening is available at Health Department clinics, no appointment required. Call 311 for clinic locations and hours of operation. Services are available to people 12 and older without parental notification and without regard to immigration or insurance status.
If you have exposed any partners to a sexually transmitted infection (including HIV), it is important to tell them so they can be tested and treated if necessary. People who want help notifying partners, or who want to do so anonymously, can find assistance by calling 311 or visiting inSPOT NYC (www.inspot.org/Newyorkcity).
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #111 on: April 23, 2010, 01:19:36 PM »
Zinc Linked to Prostate Cancer Survival. What are Good Zinc Food Sources?


Zinc Linked to Prostate Cancer Survival. What are Good Zinc Food Sources?



MedPage Today

April 22, 2010




Action Points 




    * In this study, men diagnosed with early stage prostate cancer had an increased chance of surviving the disease if they adhered to a diet rich in zinc.







    * Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.




WASHINGTON -- Men diagnosed with early stage prostate cancer have an increased chance of surviving the disease if they have eaten a diet rich in zinc, researchers said here at the annual meeting of the American Association for Cancer Research.




"Those men with high zinc intake were 74% less likely to die of prostate cancer than those with the lowest zinc intake," Mara S. Meyer, MS, a doctoral candidate at the Harvard School of Public Health, said during a poster presentation (95% CI 0.10 to 0.68, P=0.005).




Researchers also reported a trend indicating that men who consumed high levels of marine omega-3 docosahexaenoic acid were 30% less likely to die of prostate cancer than men who consumed the lowest levels of the fatty acids (95% CI 0.47 to 1.03, P=0.26).




Meyer found no apparent associations between prostate cancer-specific mortality and death from other causes involving dietary intake or saturated, monounsaturated, or omega-6 polyunsaturated fatty acids.




The researchers accessed data from the Örebro Swedish Cohort, including 525 confirmed prostate cancer cases among men living in Örebro County who were diagnosed from 1989 to 1991.




At the time of diagnosis, dietary data was collected by a food frequency questionnaire specific to the Swedish diet. Use of dietary supplements was negligible in this population, which was assembled before the introduction of PSA testing.




The researchers studied intake of zinc and fatty acids -- dividing intake into quartiles. They also noted time to death and whether death was caused by prostate cancer of some other illness.




Meyer noted that 218 men died from prostate cancer, and 257 men died from other causes. Fifty of the men in the cohort are still alive.




She said most of the men in this group ingested dietary zinc through consumption of grains.




"We did not see a relationship between zinc and mortality or disease specific mortality except among those patients who were diagnosed with an early stage prostate cancer," she said.




Twenty percent of the men diagnosed with Stage II cancer or a lower grade died of the disease, while 58% percent of these men died of some other cause.




Men in the highest quartile of daily zinc consumption averaged about 15.7 mg or more of the trace metal; those in the lowest quartile consumed 12.8 mg or less, Meyer reported.




"The role of diet in cancer is always difficult to study," commented Charles Rabkin, MD, senior investigator in the Infections and Immunoepidemiology Branch in the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Md.




"It can be challenging to tease out what is real in these studies and what is not," he told MedPage Today. "But studies such as this one by Meyer and her colleagues definitely give us some clues to pursue."



Primary source: American Association for Cancer Research

Source reference:

Meyer M, et al "Diet, inflammation and prostate cancer survival in the Orebro Prostate Cancer Survivors Cohort" AACR 2010; Abstract 5747.

---------------------------


What are Good Zinc Food Sources?




An important mineral for the body for various functions



Zinc is one of the most important minerals used by the body for various functions and fortunately, there is a wide variety of zinc food sources available naturally for you to take advantage of. To give you an idea just how important it is, zinc helps in the production of about 100 enzymes in your body, builds you a healthy immune system, maintains your senses of smell and taste and is needed for DNA synthesis.



Foods Containing Zinc



Zinc is very much associated with protein foods. Thus, you may assume that most foods high in zinc are protein-rich as well. The best sources of zinc include beef, lamb, pork, crabmeat, turkey, chicken, lobster, clams and salmon.




If you are a vegetarian, you will most probably intake less zinc that those who have meat-based diets. Good zinc food sources aside from meats are dairy products such as milk and cheese, yeast, peanuts, beans, and wholegrain cereals, brown rice, whole wheat bread, potato and yogurt. Of all these vegetarian zinc foods, pumpkin seeds offer one of the most concentrated non-meat food sources of zinc.




Zinc Foods: Foods Rich in Zinc Content



Many foods contain some amounts of zinc, but to be considered a good zinc food source, the food must contain a substantial amount of the mineral relative to the calorie content. It should also contribute at least about 10% of the Recommended Dietary Allowance in one standard serving size.



Recommended Dietary Allowances for Zinc



For adults, the RDA for zinc should be about 11 milligrams per day for adult men and 8 milligrams for women. If you are lactating or pregnant, you need to put in about 3 mg more. For children, about 5 mg is needed for 4-8 year olds, and 8 mg for 9-13 year olds, while infants need only about 3 mg.



The Truth about Zinc Nutrition



The downside of taking these high zinc foods is that no matter how much of them you take in, only a mere 15%-40% of the zinc actually gets absorbed by your body overall. This is especially true for non-meat zinc food sources. Dietary fibers and phytic acid in brain prevents the absorption of zinc in your body. Phytic acid found in your brain forms a complex with the zinc that you take in, and this compound is insoluble so that it cannot be absorbed readily by your body. Whole grains are a better source of zinc than refined grains as they have the ability to produce enzymes that can destroy phytic acid. On the other hand, the zinc you get from eating meat is four times more bio-available than in grain foods.




It has been found that increasing intake of vitamins such as Vitamin C, E and B6 and minerals such as magnesium can increase zinc absorption in the body. So, it will be a good idea to add these to your daily vitamin and mineral intake.



Risks in Taking Too Much Zinc



If you are healthy and you eat a well-balance diet, you will rarely need supplements to complete your body's zinc needs. You should be careful in taking zinc supplements because too much of zinc can be potentially harmful to your body. It has been reported that intake of more than 50 milligrams of zinc (both from diet and from supplements) can lead to improper copper metabolism, altered iron function, reduction of HDL's (good cholesterol) and reduced immune function.




Zinc is very important to your body and you should make sure that you have enough zinc food source intake to complete your dietary needs. However, as always, taking too much can lead to harsh consequences, so make sure that you only take what is needed.



http://www.nutritional-supplements-health-guide.com
« Last Edit: April 23, 2010, 01:22:40 PM by red_Dragon888 »
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #112 on: April 26, 2010, 11:35:38 AM »

I think the national HIV prevalence is 0.5% making the HIV prevalence in NYC jails of 8.7% much higher

"HIV prevalence for all inmates in the serosurvey was 5.2%: 4.7% in men and 9.8% in women (Table 2). Adjusting our serosurvey prevalence to reflect all new admissions (those with and without remnant serum) based on proportion matching to HARS, the estimated true New York City inmate prevalence would be 8.7% overall (95% CI: 8.1% to 9.2%): 6.5% in males (95% CI: 6.0% to 7.1%) and 14% in females (95% CI: 12.7% to 15.3%)."


"More than a quarter of HIV-infected jail entrants appear to be undiagnosed at admission. This is substantially higher than the 5% estimated from a 2004 New York City household serosurvey9 and more aligned with the 12%-29% estimate calculated for New York City overall10 and CDC's nationwide 21% estimate.8 The vast majority (∼90%) of undiagnosed inmates did not self-report recognized HIV risk factors (ie, MSM or IDU activity). MacGowan et al18 reported similar results: only 15% of new diagnoses in Florida, Louisiana, upstate New York, and Wisconsin jails reported IDU or MSM activity. Likewise, among Los Angeles jail entrants, Harawa et al19 found that 68% of men and 55% of woman reported no HIV risk factors......Taken together, this information confirms that increasing acceptance of routine HIV testing (ie, offering all inmates testing regardless of risk) is likely the best approach to diagnosing more of the jail entrants with undiagnosed infection.....Two thirds of inmates did not consent to HIV testing.....It is likely that more inmates would consent to testing with a more streamlined opt out approach that does not include a separate written consent for each HIV test conducted. A separate written consent is still required by New York State despite CDC recommendations for their elimination,1 including in correctional settings



In conclusion, HIV prevalence appears to have substantially decreased among New York City jail entrants; however, over one quarter of HIV-infected jails entrants are undiagnosed, representing more than 100 persons in our sample alone. Despite a 4-fold increase in jail testing, most undiagnosed infections are not identified during voluntary jail testing, largely due to low testing acceptance rates. Most undiagnosed inmates did not report recognized HIV risk factors, reinforcing the need to improve inmate acceptance of the jails' current routine testing program rather than focus on increasing efforts among inmates reporting specific behaviors. To increase inmate's acceptance of routine testing, we are working to eliminate the required separate written consent for HIV testing to allow implementation of the CDC-recommended opt out testing model."



Undiagnosed HIV Infection Among New York City Jail Entrants, 2006: Results of a Blinded Serosurvey





JAIDS Journal of Acquired Immune Deficiency Syndromes:

1 May 2010 - Volume 54 - Issue 1 - pp 93-101



Begier, Elizabeth M MD, MPH; Bennani, Yussef MPH; Forgione, Lisa MA; Punsalang, Amado PhD; Hanna, David B MS; Herrera, Jeffrey BA; Torian, Lucia PhD; Gbur, Maria MD; Sepkowitz, Kent A MD; Parvez, Farah MD, MPH

From the New York City Department of Health and Mental Hygiene, New York, NY. Dr Farah Parvez was also associated with the National Center for HIV/AIDS, Viral Hepatitis, sexually transmitted disease, and TB Prevention, Centers for Disease Control and Prevention.



Abstract




http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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« Reply #113 on: April 26, 2010, 11:36:39 AM »
Fish Oil Claims May be Snake Oil
MedPage Today
Published: April 23, 2010

Claims that fish oil supplements preserve cognition should not be swallowed hook, line, and sinker, researchers said.

In a randomized, placebo-controlled trial of nearly 900 septuagenarians, the omega-3 fatty acid supplements had no effect on cognition, according to Alan Dangour, PhD, of the London School of Hygiene and Tropical Medicine, and colleagues.

Over a two-year period, there was no difference in cognitive decline in either the fish oil or placebo arm of the study, the longest yet conducted, Dangour and colleagues said online in the American Journal of Clinical Nutrition.


Action Points 
--------------------------------------------------------------------------------

Explain to interested patients that fish oil supplements are proposed as a way to prevent cognitive decline with age.



Note that this large randomized trial found no such benefit.

"There is no evidence of an important benefit for memory or concentration," Dangour said in a statement.
Still, he cautioned that cognitive function can take years to decline, "and although this is the longest trial of its kind ever conducted, it may be that it was not long enough for any true beneficial effects to be detected among this healthy cohort of older people."


The findings come from the so-called OPAL study (for Older People And omega-3 Long-chain polyunsaturated fatty acids), which enrolled 876 healthy and cognitively sound people in Britain, ages 70 through 79.


They were randomized to get either an olive oil placebo or the combination of 200 milligrams of eicosapentaenoic acid and 500 milligrams of docosahexaenoic acid daily for two years.


Eicosapentaenoic and docosahexaenoic acid are omega-3 long-chain polyunsaturated fatty acids, commonly found in oily fish. They have been associated with cognitive benefits in observational studies, but there was no evidence of a positive effect in a recent six-month randomized trial, the researchers said.


"Current evidence of a benefit for cognitive health is not convincing," the researchers said.
In the current study, participants were tested on a range of cognitive tasks at the beginning of the trial and after 24 months, the researchers said.


The primary outcome was recall of a 16-word list from the California Verbal Learning Test, but the researchers also tested immediate and delayed recall, spatial memory, processing speed, reaction time, and executive function, among other things.


After 24 months, Dangour and colleagues found, participants getting the fish oils had more of them in their blood (at P<0.001 for both comparisons) than did those in the placebo arm.


At the same time, placebo participants had higher serum concentrations of two omega-6 fatty acids as well as two components of olive oil.


But there were no significant differences between the groups on the California Verbal Learning Test, they researchers said.


After adjustment for baseline cognitive function, age, sex, and age at leaving full-time education, the average difference between the fish oil and placebo arms in the total number of words recalled over three trials in the California Verbal Learning Test was minus 0.5 words.


The average difference in recall after a 20-minute delay was 0.1 words.


There was also no significant difference in any of the other cognitive function tests, the researchers said.
Adverse events were minor -- typically annoyances as flatulence, belching, abdominal discomfort, and loose stools -- and were not significantly different between the groups, the researchers found.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #114 on: April 30, 2010, 10:25:36 AM »
NATAP: Vitamin D Deficiency in HIV

I got mines, do you got yours...

NATAP http://natap.org/
_______________________________________________


High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients - (04/29/10)

AIDS:
15 May 2010

from Jules: we don't know the effect of vitamin D supplementation in HIV+ individuals; if vitamin D levels are getting eaten up in HIV+ individuals which appears to be the case, perhaps by HIV or HAART or poor absorption, then will even high-dose supplentation have a lasting affect on raising levels. We need to find out through study why vitamin D is gettibg eaten up in HIV.

"we suggest systematic screening for vitamin D deficiency in all HIV-positive patients..... With 42-52% in spring and 14-18% in fall, vitamin D deficiency was highly prevalent in our HIV-positive patients.....A comparison with deficiency rates in the general Swiss population is difficult, as recent data are missing. However, the rate of vitamin D deficiency in our HIV-positive cohort was clearly higher than the 6-15% rate found in the only assessment in the general Swiss population during winter [25]. Consistent with earlier reports [21], non-white ethnicities with darker skin pigmentation, in particular black patients, were most strongly affected by vitamin D deficiency.....The role of vitamin D supplementation in HIV-positive patients, and specific treatment goals in particular, must be defined by prospective studies with HIV-specific endpoints such as disease progression or change in CD4 cell counts. Also, the impact of NNRTIs on 25(OH)D and TDF on 1,25(OH)2D needs further consideration."
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #115 on: May 04, 2010, 11:18:30 AM »
MDs Contribute to the HIV Epidemic. Seriously.
huffingtonpost.com


At first I thought it was a fluke. But then I heard the same story told again. Different friend. Different doctor. Same problem.


I have been telling students, peers, and friends to get tested for HIV since I was fifteen years old. At the University of Pennsylvania, I volunteered at our anonymous HIV testing site. Aside from me, only two other individuals were tested at my site during my six month tenure. Clearly, the stigma surrounding HIV testing was a major obstacle.


But now, as my friends are older and not necessarily having monogamous relationships (not that they were back then, either), the people in my life are far more responsible about knowing their sexual health status. Though it still causes them great anxiety, they know that an HIV test is part of what it takes to be a sexually healthy person. I was ecstatic when my friend Jane (names have been changed to protect the responsible parties) told me that she was going to request an HIV test at her next check up.


And then last night, Jane called me. "So, I did it. Got the test, and it's negative. But I do need to tell you something." (I waited nervously.)


"Okay...I'm listening."


"So I asked the doctor for an HIV test. His response? 'Why? I don't think that you need to be tested. You're fine.' I said, But I am a single woman who is sexually active. I would like the test. Don't you test other patients? He replied, 'Yes, but only if they ask.'"


Holy crap. That doctor should have responded. "That's great, Jane. Very responsible. Sure, I'll test you.Is there anything that you would like me to know? Any other tests you feel like you want to have?"
But no. Instead Jane hears, "I don't think that you to be tested. You're fine."


WTF is going on???


The scary thing is that this is the second time I have heard this story this month. Haven't we learned (albeit the hard way) that you can't tell who has HIV just by looking at him/her? Haven't we learned that you cannot make assumptions about a patient based on what you perceive their lifestyle/orientation/gender to be?


Apparently not.


So this is my call to action: Patients speak up! Ask to be tested. And doctors - stop making it so damn difficult for people to be responsible. Give patients the test when they ask for it. Don't try to talk them out of it. And most importantly, offer the test when you are doing a general physical examination. Spend the extra thirty seconds that it takes to ask the question and send the nurse in to draw that blood. Otherwise, you are not part of the solution; you are part of the problem.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #116 on: May 04, 2010, 11:19:51 AM »
Vitamin D Deficit Common Among Southern Teens
MedPage Today
Published: May 03, 2010


Although they live in a relatively sunny climate, adolescents in southern states often have low blood levels of vitamin D, particularly if they are black, overweight, or inactive, a new study found.
Of adolescents tested, 56.4% had vitamin D insufficiency (<75 nmol/L) and 28.8% had deficiency (≤50 nmol/L), according to an online report in the May 3 Pediatrics.


Action Points
Explain to interested parents that even adolescents living in sunny regions appear to be at risk for low vitamin D levels.


Note that adolescents who were black, overweight or inactive were at higher risk for low vitamin D levels.
Compared to white youths, black youths had significantly lower blood plasma levels of 25-hydroxyvitamin D, regardless of the season:
Summer, 50.7 ± 4.0 vs 104.3 ± 4.0 nmol/L
Fall, 54.4 ± 4.0 vs 96.8 ± 2.7 nmol/L).
Winter, 35.9 ± 2.5 vs 77.4 ± 2.7 nmol/L
Spring, 46.4 ± 3.5 vs 101.3 ± 3.5 nmol/L
"Our data demonstrate that low vitamin D status is common among adolescents residing in the southeastern region and is related to various adiposity and lifestyle factors," Yanbin Dong, MD, PhD, of the Medical College of Georgia, and colleagues wrote.


"Taken together, these findings suggest that low vitamin D status is a growing national problem for adolescents in the United States, regardless of latitude."


Several studies have documented low vitamin D levels in children and adolescents living at northern latitudes, including communities in Pennsylvania, New Jersey, Ohio, Massachusetts and Maine.
Although exposure to sunlight helps the body produce vitamin D, data from the National Health and Nutrition Examination Survey has suggested that children living in southern states might also suffer from vitamin D deficiency.


To determine if that was the case, Dong and colleagues measured blood serum vitamin D levels in 559 adolescents from 14 to 18 years old, who were recruited from high schools in and around Augusta, Ga. (latitude 33.44°N) from January 2001 to June 2005. The researchers also measured the youths' fat tissue, physical activity and cardiovascular fitness.


Of the subjects, 45% were black and 49% were female.


After adjusting for age, gender, race, season, height and sexual maturation, the researchers found that all fat measurements, including BMI percentile (P=0.02), waist circumference (P<0.01), total fat mass (P<0.01), percentage of body fat (P<0.01), visceral adipose tissue (P=0.015) and subcutaneous abdominal adipose tissue (P=0.039), were associated with low vitamin D levels.


Participants who engaged in more vigorous physical activity (P<0.01) and had better cardiovascular fitness (P=0.025) were more likely to have higher levels of vitamin D.


"As an easy, inexpensive, adiposity measure, BMI percentiles could potentially be used alone for study of the relationship between adiposity and vitamin D levels in future studies," Dong and colleagues wrote. "Our data suggest that the relationship between 25-hydroxyvitamin D levels and adiposity in adolescents is independent of the site of fat content and fat distribution."


They noted that some scientists attribute low vitamin D levels observed among blacks to reduced skin synthesis caused by greater skin pigmentation, but Dong and colleagues proposed that the difference also could be related to relatively high rates of obesity in black populations.


The authors cautioned their analysis lacked information on the adolescents' sun exposure and dietary consumption of vitamin D and calcium.


They also noted that they did not measure individuals' plasma 25-hydroxyvitamin D levels in every season, which might have caused them to overlook seasonal variations of vitamin D levels.




"Prevalence of Low Vitamin D Status
Detailed prevalence rates of low vitamin D status, that is, insufficiency (</=75 nmol/L), deficiency (</=50 nmol/L), and severe deficiency (</=25 nmol/L), according to season, race, and gender
are shown in Table 2. The overall prevalence rates of vitamin D insufficiency and deficiency were 56.4% and 28.8%, respectively (Table 2). Vitamin D insufficiency rates were observed to
be 94.3% and 83.1% in black girls and boys, respectively, compared with 29.6% and 30.3% in white girls and boys. Vitamin D deficiency rates were found to be 73.8% and 46.9% in black girls and boys, respectively, compared with only 2.6% and 3.9% in white girls and boys. Severe vitamin D deficiency
was found only in black adolescents (5.2%). In summer, no white participants were found to have 25-
hydroxyvitamin D levels of </=50 mol/L, but 55% of black adolescents were shown to have levels indicative of vitamin D deficiency and 88.1% vitamin D insufficiency."
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #117 on: May 05, 2010, 05:32:43 PM »


Successful initiation of an anal cancer screening and treatment program at a New York City HIV clinic






AIDS:

24 April 2010

Correspondance



NYS Guidelines recommendations on anal pap smears
Click on "Clinical Guidelines" and you'll see current NYS DOH guidelines in ... multiple sexual partners, HPV infection, and receptive anal intercourse. ...
www.natap.org/2010/HIV/032510_01.htm


Tider, Diane S; Caprio, Gabriela Rodriguez; Gaisa, Michael; Klein, Robert S; Goldstone, Stephen E

Mount Sinai School of Medicine, New York, New York, USA.



We read with interest the correspondence by Shalev et al. [1]'s regarding new New York State AIDS Institute guidelines for anal cancer screening and treatment in HIV-positive persons. The authors assert that the guidelines would require almost 50% of their patients to undergo routine anal screening, which is a large figure considering the absence of Centers for Disease Control directives or national standards. They noted that such an endeavor takes time and resources, and questioned the justification of such expenditures, in advance of the creation of broader policy.




At Mount Sinai, we have spent the last year initiating an anal cancer screening and treatment program within our HIV clinic, in response to the New York State guidelines. On the basis of the proven reduction of morbidity and mortality with cervical Papanicolaou (Pap) testing, recommendations were extended in 2007 to include anal cancer screening with annual visual and digital anal exams for all HIV-positive adults, and annual anal Pap testing for men who have sex with men, women with prior abnormal cervicovaginal histology, and persons with prior anogenital condyloma. Those with abnormal findings require follow-up with high-resolution anoscopy (HRA), with biopsy and treatment when appropriate [2].




Human papillomavirus (HPV), an established carcinogen and causative factor in cervicovaginal [3–5] and anal cancers [6–14], is particularly virulent in HIV-positive persons [15]. Cervical cancer is an AIDS-defining malignancy [16], and HPV-related anal, gynecologic, penile, and oropharyngeal cancers have all been associated with HIV/AIDS [6]. Although rare in the general population [17], anal cancer is increasingly prevalent in HIV-positive persons on highly active antiretroviral therapy [18].




In 2008, we successfully applied for Ryan White Title III HIV Capacity Development funding for 1 year to initiate an anal screening and treatment program within our New York City HIV clinic. We identified an infectious diseases physician interested in HRA, and partnered with an expert in the field for training and oversight. We collaborated with our institution's colon and rectal surgery department to streamline the referral process for patients requiring surgery. Our overall goal was to diagnose and treat as many patients as possible in clinic, rather than in surgery, where anoscopy and ablation had been performed in the past.




We purchased equipment and supplies for anal Pap testing, HRA, and ablation, including swabs, cytobrushes, and Thin-Prep Pap Test collection kits, Baby Tischler biopsy punches, a universal power procedures examination table that converts to the knee–chest position, a state-of-the-art colposcope, and an infrared coagulator. A procedure room was identified and stocked in the clinic.




Primary care providers in the clinic were educated on the new guidelines and trained in performing anal Pap smears via literature and an instructional DVD from Johns Hopkins University. Anal Pap smears were added as annual visit quality indicators. We developed instruction sheets on the anal Pap smear technique and ordering, and adapted a referral algorithm to post in examination rooms. Finally, we developed a low health literacy brochure to help patients understand the purpose and significance of anal Pap smears, HRA, and the results obtained.




In a short period of time, providers integrated anal Pap testing into their practice. An initially high rate of inadequate specimens lead to discussions about technique and practice. After consulting with our pathologists, inconsistencies in cytology reporting were remedied, and providers were educated on the interpretation and implications of anal cytology results.




In just under a year, 212 patients (47% women) underwent anal Pap testing. Similar to the forecasted rates of Shalev et al. [1], 44% of adequate cytology specimens were abnormal and were scheduled for HRA. Patients with extensive disease on HRA are referred to colon and rectal surgery clinic. Patients with more limited disease are treated in-office with infrared coagulator ablation [19–21].




Although the initiation of our anal cancer screening program took substantial time, effort, and funding, over the last year, our team has built a successful and dynamic program to meet New York State AIDS Institute guidelines. We believe that the preliminary evidence justifying the need for this clinical service is convincing, even if it has not yet proven cost-effective in large multicenter clinical studies. Although further studies are warranted, epidemiologic data and anecdotal reports of substantial morbidity and mortality in young, HIV-infected persons from this treatable condition should not await definitive cost–benefit studies before action is taken. At Mount Sinai, we now provide a valuable clinical service to patients at high risk for anal dysplasia.

---------------


Targeted anal cancer screening in HIV-infected patients: prevalence of screening indicators



AIDS:

24 April 2010 6e9a1

Correspondance



Shalev, Noga; Olender, Susan A; Chiasson, Mary Ann

aDivision of Infectious Diseases, Columbia University Medical Center, USA




bPublic Health Solutions, New York, New York, USA.



We thank Tider et al. [1] for their response to our research letter. The incidence of anal cancer in HIV-infected individuals is far higher than the general population but the utility of screening has not been established [2]. As medical providers to HIV-infected patients, we share the respondents' concerns regarding the excessive morbidity and mortality associated with anal carcinoma. Tider et al. [1] provide a detailed description of anal cancer screening ‘scale up’ in an HIV clinic. However, the authors do not share information about key outcomes, such as the number of patients referred to high-resolution anoscopy, the proportion referred who underwent the procedure, or the correlation between cytological and anoscopic findings. In addition, neither the proportion of patients undergoing treatment, nor treatment response data are presented. These data are essential for guiding clinician practice.




Our concerns about anal cancer screening rest on the fear that screening will result in unnecessary diagnostic work-up and treatment without decreasing morbidity and mortality. As was recently illustrated by the US Preventive Service Task Force's revised recommendations on the use of mammograms [3], the benefit of screening is far more nuanced than our desire to prevent illness.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #118 on: May 05, 2010, 05:33:36 PM »
Pharmasset shows promising PhIIa hep C data
May 4, 2010


Pharmasset showed a promising batch of mid-stage data for its hepatitis C therapy and promised to swiftly pivot into a Phase IIb trial that could provide longer-term feedback on efficacy and safety.


After 28 days of therapy, 88 percent of patients taking 100 mg of PSI-7977 had undetectable levels of the virus. That figure rose to 94 percent at a 200 mg dose and 93 percent for 400 mg. That compares to only 21 percent of the patients in the placebo group whose virus levels dropped below the detection level.


Most adverse events reported were mild with a few moderate complaints. No serious side effects were recorded. Princeton, NJ-based Pharmasset's shares were down slightly this morning.


"Our platform technology continues to generate nucleoside/tide analogs with a high degree of efficacy, high barrier to resistance, and a safety profile that we believe differentiates them from other classes of direct acting antivirals," said Pharmasset CMO M. Michelle Berrey. "We plan to quickly progress PSI-7977 into Phase IIb studies starting in the fourth quarter 2010, to generate longer term efficacy and safety data."


- check out Pharmasset's press release
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #119 on: May 05, 2010, 05:35:12 PM »
NATAP http://natap.org/
_______________________________________________

"In summary, this pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected individuals on stable ART who have low HDL-c."


Short-term effects of extended-release niacin on endothelial function in HIV-infected patients on stable antiretroviral therapy



AIDS:

24 April 2010



Chow, Dominic C; Stein, James H; Seto, Todd B; Mitchell, Carol; Sriratanaviriyakul, Narin; Grandinetti, Andrew; Gerschenson, Mariana; Shiramizu, Bruce; Souza, Scott; Shikuma, Cecilia

aHawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA

bDivision of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA

cPublic Health Sciences, University of Hawaii, Honolulu, Hawaii, USA.



Abstract




Objective: To assess the short-term effects of extended-release niacin (ERN) on endothelial function in HIV-infected patients with low high-density lipoprotein-cholesterol (HDL-c) levels.




Methods: Randomized controlled study to determine the short-term effects of ERN on endothelial function, measured by flow-mediated vasodilation (FMD) of the brachial artery, in HIV-infected adults with low HDL-c. Participants on stable HAART with fasting HDL-c less than 40 mg/dl and low-density lipoprotein-cholesterol less than 130 mg/dl were randomized to ERN or control arms. ERN treatment started at 500 mg/night and titrated to 1500 mg/night for 12 weeks. Controls received the same follow-up but were not given ERN (no placebo). Participants were excluded if they had a history of cardiac disease, uncontrolled hypertension, diabetes mellitus, or were on lipid-lowering medications such as statins and fibrates. Change in FMD was compared between arms with respect to baseline HDL-c.




Results: Nineteen participants were enrolled: 89% men, median age 50 years, 53% white/non-Hispanic, median CD4 cell count 493 cells/μl, and 95% of them had HIV RNA below 50 copies/ml. Participants receiving ERN had a median HDL-c (interquartile range) increase of 3.0 mg/dl (0.75 to 5.0) compared with −1.0 mg/dl in controls (−6.0 to 2.5), a P value is equal to 0.04. The median change in FMD was 0.91% (−2.95 to 2.21) for ERN and −0.48% (−2.65 to 0.98) for controls (P = 0.67). However, end of study FMD for ERN was significantly different from controls after adjusting for baseline differences in FMD and HDL-c, 6.36% (95% confidence interval 4.85–7.87) and 2.73% (95% confidence interval 0.95–4.51) respectively, a P value is equal to 0.048.




Conclusion: This pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected patients with low HDL-c.



Introduction




The incidence of myocardial infarction (MI) in HIV-infected individuals has been increasing. Although much of the coronary artery disease (CAD) risk in the HIV population has been attributed to elevated levels of low-density lipoprotein-cholesterol (LDL-c) and hypertriglyceridemia, low levels of high-density lipoprotein-cholesterol (HDL-c) also contribute to CAD risk. In the general population, low serum levels of HDL-c are associated with increased risk for MI, restenosis after angioplasty, sudden cardiac death, and stroke [1–3]. The primary mechanism by which HDL-c exerts its atheroprotective effect is believed to be reverse cholesterol transport; however, HDL-c also has antioxidant effects [4]. Additionally, HDL-c has direct arterial effects that help preserve endothelial function. Endothelial dysfunction is an early phenomenon in atherosclerosis that precedes structural changes of the arterial wall and clinical manifestations of CAD [5]. This protective effect of HDL-c on endothelium-dependent vasoreactivity may depend on the binding of HDL-c to scavenger receptor class B type I and subsequent stimulation of nitric oxide formation [6]. HDL-c activates both extracellular signal-regulated kinase 1/2 and Akt, resulting in enhanced stability of endothelial nitric oxide synthase [7].




In dyslipidemic HIV-infected patients on stable antiretroviral therapy (ART), low levels of HDL-c have been associated with endothelial dysfunction [8]. Moreover, use of statins in HIV-infected patients on ART improves endothelial function [9]. We hypothesized that increases in HDL-c associated with the use of niacin also would improve endothelial function in HIV-infected individuals. Therefore, we conducted a pilot study to assess the effects of niacin on endothelial function in HIV-infected patients with low HDL-c levels.



Discussion




In this pilot study, we demonstrated that HIV-infected patients on stable ART with low HDL-c had improved brachial artery FMD after 12 weeks of ERN. The improvement in FMD was more significant in patients with low baseline HDL-c. In individuals with HIV, low HDL-c levels increase risk of future CAD [12–14]. Changes in HDL-c with ART also seem to affect short-term CAD [15]. Our study is consistent with recent studies on individuals without HIV infection, showing that interventions targeted at raising HDL-c levels may have vascular benefits. Indeed, two studies [16,17] have shown that in individuals with low HDL-c, use of ERN can improve FMD. Similarly, ERN has been shown to significantly regress carotid intima–media thickness [18]. Our study is the first to determine the effect of niacin on endothelial function in HIV-infected individuals. This is a clinically relevant finding, as many patients with HIV and dyslipidemia have low HDL-c, and the effects of raising HDL-c on endothelial function in patients with HIV have not been investigated previously. Also, niacin's effects on lipids in patients with HIV seem to be less than observed in the general population [19].




Niacin can inhibit vascular inflammation by decreasing endothelial reactive oxygen species production and subsequent LDL-c oxidation and inflammatory cytokine production, key events involved in atherogenesis. Potential mechanisms of the vascular protective effects of HDL-c have been described [20]. HDL-c enhances reverse cholesterol transport, promoting the efflux of cholesterol from atherosclerotic plaque rupture, thus promoting stabilization [21]; HDL-c and its associated proteins attenuate the formation of the highly atherogenic oxidized LDL-c species previously shown to impair endothelial function [22]; HDL-c stabilizes prostacyclin, an important vasodilator and platelet inhibitor [23]; and HDL-c may augment the ability of the endothelium to produce nitric oxide [16]. In addition to the protective effects of HDL-c, niacin helps increase LDL-c particle size, which also may improve endothelial function. Our finding supports the paradigm that niacin-induced increases in HDL-c contribute to improvements in endothelial function in participants with low HDL-c. Of interest, in ACTG study A5152s, positive correlations were observed between ART-associated increases in HDL-c, large HDL-c particles, and FMD (personal communication).




There are several limitations to our study. First, this was an unblinded pilot study with a small sample size and its results require verification, as well as evaluation of the mechanism for these observations. Second, the increase in HDL-c was less than that would be predicted based on data in non-HIV-infected cohorts [16], although this study was of short duration (all treated participants were at the maximal daily dose of 1500 mg of ERN for only 4 weeks), and niacin's beneficial effects on HDL-c levels can continue to increase up to 36 weeks after maximum dose titration [24].




In summary, this pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected individuals on stable ART who have low HDL-c.



Results



Baseline characteristics




The demographic and clinical characteristics of the 19 participants are presented in the Table 1. Participants consisted of 17 men and two women, with a median age of 50 years (range 28–65 years). Four were current and seven were former smokers. The median CD4 cell count was 493 cells/μl (range 280–1096). All participants had undetectable HIV viral loads except for one participant with a viral load of 1520 copies/ml. The majority of participants (47%) were on an efavirenz-based regimen, whereas 42% were on a protease inhibitor-based regimen. A nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen was used in 60% of the ERN group compared with 44% of controls; a protease inhibitor-based regimen was used in 30% of ERN and 56% of controls. One participant in the ERN group was on an NRTI-only regimen. At baseline, there were differences (P < 0.10) between the arms in FMD, nitroglycerin-mediated dilation (NTGMD), and HDL-c.




All participants achieved the titrated dose of ERN of 1500 mg daily. Only one participant receiving ERN developed serious flushing (grade 2), which was attributed to the participant accidentally taking twice the prescribed dose. This flushing resolved after the ERN dose was reduced. There were no grade 3 or higher adverse events during the study in either group.




After 12 weeks, participants receiving ERN had a median HDL-c (interquartile range) increase of 3.0 mg/dl (0.75 to 5.0) compared with −1.0 mg/dl in controls (−6.0 to 2.5), P value is equal to 0.04. There was no significant change in brachial diameters; the median change in participants receiving ERN was 0.00 mm (−0.01 to 0.03) compared with −0.01 mm in controls (−0.02 to 0.02), P value is equal to 0.56. The median change in FMD from baseline to week 12 was 0.91% (−2.95 to 2.21) for those on ERN vs. −0.48% (−2.65 to 0.98) for controls (P = 0.67). However, after adjusting for baseline differences in FMD and HDL-c, there was a statistically significant increase in FMD in participants receiving niacin (P = 0.048, see Fig. 1). Participants with low HDL-c had a more dramatic improvement in FMD with niacin. In participants with HDL-c 35 mg/dl or less, the adjusted end of study FMD was 8.4% with 95% confidence interval (CI) (6.7 to 10.1) for the niacin group and 4.4% with 95% CI (3.18 to 5.68) for the control group (P = 0.01). There were no differences in NTGMD between the two arms, even after adjusting for baseline NTGMD and HDL-c.



Methods




This was a randomized controlled study evaluating endothelial function, measured by flow-mediated vasodilation (FMD) of the brachial artery, in HIV-1-infected adults with low HDL-c before and after 12 weeks of treatment with extended-release niacin (ERN). Participants randomized to the treatment arm received ERN (Niaspan; Abbott Laboratories, Abbott Park, Illinois, USA) starting at 500 mg per night and titrated to a maximum tolerated dose (not exceeding 1500 mg per night) over 8 weeks. Participants in the control arm received the same follow-up as the treatment arm but were not be given ERN (no placebo) and were instructed to not take any supplemental niacin. CD4 cell count, HIV RNA viral load, FMD, lipid parameters, insulin sensitivity, and C-reactive protein were obtained at baseline and after 12 weeks for both control and treatment arms.




Participants were eligible for the study if they were HIV-infected and were at least 18 years of age. Participants must have been on stable HAART for at least 6 months prior to study entry and have a HDL-c below 40 mg/dl and LDL-c below 130 mg/dl. Participants were excluded if they had cardiac disease, uncontrolled hypertension, pregnancy, or diabetes mellitus. Participants were ineligible if they were on nitrates, metformin, or thiazolidinediones. Treatment with lipid-lowering drugs such as statins and fibrates were excluded. A pharmacist prepared a computer-generated single-block randomized treatment list to determine each patient's treatment assignment. The study pharmacist did not participate in the selection and assessment of patients or the collection of any trial data. This study was approved by the Institutional Review Board of University of Hawaii. All participants provided informed consent.




Endothelial function was assessed by ultrasound brachial artery reactivity testing. Testing was performed in the morning. Participants were required to fast for 12 h. Those who regularly used tobacco products refrained for at least 8 h. After 10-min rest in a temperature-controlled room (70–76°F), the diameter of the right brachial artery and baseline blood flow were measured with a high-resolution linear array vascular ultrasound transducer (Siemens Medical Solutions Inc., Mountain View, California, USA). Increased forearm blood flow was induced by inflating a pneumatic blood pressure tourniquet placed around the widest part of the forearm and inflated to 250 mmHg. This was followed by deflation after 5 min. Repeat brachial artery diameter and blood flow scans were obtained immediately thereafter. Twenty minutes were allowed for vessel recovery and repeat resting brachial artery diameter and blood flow scans were obtained. Sublingual nitroglycerin (400 μg) was administered, and final scans were performed after 3 min. Each study was recorded digitally and sent to the University of Wisconsin Atherosclerosis Imaging Research Program core ultrasound laboratory in Madison, Wisconsin, USA. Brachial artery diameters were measured in triplicate by a single blinded reader [8,10,11].




The primary objective was to assess the change in FMD with respect to 12 weeks of ERN vs. control. The Shapiro–Wilks normality test was used to assess the homogeneity of variances between and within the study arms. Categorical variables were compared using the χ2 test. Continuous variables were analyzed by Wilcoxon rank test. For between-group differences, a two-way analysis of covariance (ANCOVA) for both arms was conducted and controlled for within patient correlation. To control for the effects of baseline FMD and HDL-c, a multivariate ANCOVA was performed. A two-sided probability of P value is less than 0.05 was used to determine statistical significance. All statistical analyses were performed using the JMP statistical program (SAS Institute Inc., Cary, North Carolina, USA).

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #120 on: May 07, 2010, 10:10:19 AM »
Clue Found to HIV 'Elite Controllers'

MedPage Today

May 06, 2010

Action Points 

    * Explain to interested patients that some people with HIV progress slowly if at all to AIDS, so-called "elite controllers," and this study suggests a reason for that phenomenon.




Researchers believe they have found an important clue in the mystery of the elite controllers -- patients whose HIV infections progress only slowly, if at all, to full-blown AIDS.




A combination of computer modeling and human studies suggests that the elite controllers have killer T cells that are more sensitive to fast-mutating viruses such as HIV, according to Bruce Walker, MD, of Massachusetts General Hospital in Boston, and colleagues.




The result appears to be a more robust immune response in the early stages of HIV infection, Walker and colleagues wrote online in Nature.




Those T cells arise because -- perhaps paradoxically -- the immune system molecules that prime them do a relatively poor job, failing to present large numbers of self-proteins, the researchers said.




The finding derives from the observation that some immune system gene variants -- or HLA class I alleles -- are "markedly enriched" in elite controllers, the researchers said.




The strongest association is for an allele dubbed HLA-B57, so Walker and colleagues analyzed its role in preparing T cells in the thymus.




In general, the HLA molecules bind to and then present a range of self-proteins to the nascent T cell; a cell that reacts too strongly to a self-protein is prompted to self-destruct.




In computer algorithms, Walker and colleagues showed that a molecule associated with HLA-B57 -- dubbed HLA-B*5701 -- only presents about 70,000 of the roughly 10,000,000 possible self-protein sequences to a nascent T cell.




In contrast, a molecule that doesn't protect against HIV -- HLA-B*0701 -- presents about 180,000.




The result, the researchers argued, is that T cells in people with the HLA-B57 genes recognize more peptides once they leave the thymus and are more responsive to small mutations of sequences they recognize.




A series of computer experiments suggested that the argument is correct, they said, and "compelling experimental data" from another group showed the effect actually occurs in humans.




Indeed, they said, "we predict that HIV-infected individuals with HLA alleles that bind fewer self-peptides are more likely to control viral loads to low values."




To test the prediction, they examined two HLA-typed cohorts of people with HIV, including 1,110 controllers with less than 2,000 HIV particles per milliliter of serum without the use of antiretroviral therapy and 628 progressors with viral loads exceeding 104 per milliliter.




Three HLA molecules were significantly associated with nonprogression and two with progression, they found:




    * For HLA-B*0702, the odds ratio for progression was 1.90, which was significant at P=0.0001.

    * As well, HLA-B*3501 had an odds ratio for progression of 1.95, significant at P=0.0007.

    * On the other hand, HLA-B*5701 was protective, with an odds ratio of 0.28, significant at P=10-8.

    * The same was true of two other variants, HLA-B*5703 and HLA-B*2705, with odds ratios of 0.13 and 0.45, respectively. They were significant at P=2x10-7 and P=0.0001, respectively.




The nonprotective molecules were shown to bind to more self-peptides than the protective molecules "in support of our predictions," the researchers noted.




One implication is that people with the protective alleles should also do better when faced with other fast-mutating viruses. Walker and colleagues said that HLA-B57 is, in fact, protective against hepatitis C.




Another implication is that T cells primed by HLA-B57 molecules should be more prone to recognizing self-peptides, possibly leading to autoimmune reactions. And in fact, they noted, HLA-B57 has been associated with autoimmune psoriasis and hypersensitivity reactions.




The study is "remarkable" for its breadth, according to Nobel laureate David Baltimore, PhD, of the California Institute of Technology in Pasadena, Calif.




"It starts from a clinical observation, integrates it with experimental observations, generates a valuable model, and derives from the model a deep understanding of the behavior of the human immune system," Baltimore said in a statement.




"Rarely does one read a paper that stretches the mind so surprisingly far," he said.




Walker and colleagues noted that while such broadly reactive T cells are not common in people with other HLA types, they do exist and vaccine strategies should aim at activating them.
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Re: http://natap.org/
« Reply #121 on: May 07, 2010, 10:11:17 AM »
Rate of Primary Liver Cancer Type Still Climbing
MedPage Today
Published: May 06, 2010
Rates of hepatocellular carcinoma in the U.S. continue to increase, according to the CDC.

From 2001 to 2006, the rate of the disease rose from 2.7 per 100,000 to 3.2 (P<0.01), CDC researchers reported in the May 7 issue of Morbidity and Mortality Weekly Report.

The largest annual percentage changes occurred in whites (3.8%), blacks (4.8%), and individuals in their 50s (9.1%).

Cases increased for both genders, although the annual percentage change was significantly higher in men (3.6% versus 2.3%, P&l t;0.05).

The findings indicate that long-term increases in cases of hepatocellular carcinoma -- of which more than three-quarters are caused by infection with hepatitis B or hepatitis C virus -- continue, according to the researchers.

"Development of viral hepatitis services, including screening with care referral for persons chronically infected with HBV or HCV, full implementation of vaccine-based strategies to eliminate hepatitis B, and improved public health surveillance are needed to help reverse the trend in hepatocellular carcinoma," they wrote.

The researchers analyzed data from the CDC's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) surveillance system.

Only microscopically con firmed cases of hepatocellular carcinoma were included, which, according to an accompanying comment from the MMWR editors, likely yielded more conservative estimates than previous analyses.

From 2001 to 2006, there were 48,596 cases identified, with a median age of 64 at diagnosis (62 for males and 69 for females).

The average annual rate of hepatocellular carcinoma was 3.0 per 100,000. It increased by 3.5% a year.

Individuals in their 70s were most affected, with a rate of 13.7 per 100,000, followed by those in their 80s (10.0), 60s (9.6), 50s (6.8), and 40s (2.1). Cases were infrequent in the younger age groups.

The incidence rate during the study period was about three times higher in males th an in females (5.0 versus 1.3 per 100,000), with a larger annual inc rease in men.

The racial/ethnic group most affected was Asians/Pacific Islanders (7.8 per 100,000), followed by blacks (4.2), American Indians/Alaska natives (3.2), and whites (2.6). Rates increased over the study period for white and black individuals only.

The rate rose for both Hispanic and non-Hispanic individuals, with annual percentage changes of 3.6% and 1.7%, respectively (P<0.05 for both).

The report also provided the first state-specific information on hepatocellular carcinoma trends.

Disease rates ranged from 1.4 per 100,000 in South Dakota to 5.5 in Hawaii. Eleven states had significant increases from 2001 to 2006, with the largest annual percentage changes in Okla homa (11.7%), Iowa (9.0%), and Georgia (7.4%).

The MMWR editors listed three limitations of the analysis, including possible misclassification of race and ethnicity, the lack of national data on specific Asian subgroups, and the fact that cancer registries do not routinely collect information on etiologic factors for hepatocellular carcinoma, including chronic viral hepatitis.


Primary source: Morbidity and Mortality Weekly Report
Source reference:
O'Connor S, et al "Hepatocellular carcinoma -- United States, 2001-2006" MMWR 2010; 59: 517-20.
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Re: http://natap.org/
« Reply #122 on: May 07, 2010, 10:14:04 AM »
Merck and The ADAP Crisis Task Force Announce Key Initiatives to Help Provide Funding Relief to AIDS Drug Assistance Programs (ADAPs) across the U.S.
 
 
 
  Download the PDF here
 
Price Freeze of ISENTRESS® (raltegravir) tablets for ADAPs Through 2013 and Acceleration of Rebate Payments to States among Important Initiatives Highlighted
 
Press release by Merck & NASTAD
 
WHITEHOUSE STATION, N.J., May 5, 2010 -Today, Merck & Co., Inc., and the ADAP Crisis Task Force (ACTF) announced a series of key initiatives to help struggling state AIDS Drug Assistance Programs (ADAPs) continue to provide people living with HIV access to medicines.
 
The ACTF is pleased that, among these initiatives, Merck is:
 
- Extending the price freeze of ISENTRESS® that was first established with the ACTF in 2008 to eligible ADAPs through Dec. 31, 2013.
- Extending the price freeze on CRIXIVAN (indinavir sulfate) capsules that was first established with the ACTF in 2003 to eligible ADAPs through Dec. 31, 2013.
- Working with the ACTF to provide expanded financial relief to eligible ADAPs through increased discounts for ISENTRESS and CRIXIVAN.
- Expediting the processing of state rebate claims to speed up rebate payments to eligible ADAPs.
- Working with the National Alliance of State and Territorial Directors (NASTAD) to find solutions to provide technical assistance to ADAP programs.
 
Expansion of Special Pricing Program for ISENTRESS and CRIXIVAN and extension of price freeze to eligible ADAPs through 2013
 
The ACTF, a group of state ADAP and AIDS directors that is convened by NASTAD, requested that drug companies consider implementation of cost control measures, such as a price freeze of HIV drugs to ADAPs to help mitigate the current financial crises. In response, Merck established an expanded Special Pricing Program for its HIV medicines for eligible ADAPs. The expanded Special Pricing Programs for ISENTRESS and CRIXIVAN will begin July 1, 2010 and extend through Dec. 31, 2013. The price freeze extension follows Merck's earlier agreement with the ACTF in 2008 to freeze the price of ISENTRESS to eligible ADAPs at its launch price. The extension of its price freeze on CRIXIVAN to eligible ADAPs will also last through Dec. 31, 2013. When it announced its voluntary price freeze in 2003, Merck was the first company to freeze the price of an anti-retroviral (ARV) drug to ADAPs. Merck will reassess these programs in 2014, after implementation of the U.S. government's newly expanded Medicaid program and subsidized private health insurance plans mandated by health care reform legislation (Patient Protection and Affordable Care Act).
 
Fast pay of rebates and technical assistance
 
In addition to the expanded Special Pricing Program for ISENTRESS and CRIXIVAN, Merck is committed to assisting eligible ADAPs with cash flow and to reducing the number of patients waiting to receive treatment. As such, the Company has changed its existing state invoice payment process to accelerate the payment of Merck rebates to eligible ADAPs.
 
Merck's patient assistance programs in the U.S.
 
Merck's commitment to patients' access to its products is evidenced through its HIV SUPPORT program, which helps patients who have been prescribed ISENTRESS or CRIXIVAN by providing personalized support and patient advocacy regarding individual reimbursement issues. The SUPPORT program also offers patient assistance, which may include providing ISENTRESS or CRIXIVAN free of charge to eligible patients. Information about the SUPPORT Program can be obtained by calling 1-800-850-3430 or at www.isentress.com..
 
Patients who are on ADAP waiting lists or who are awaiting ADAP approval may be eligible to receive ISENTRESS or CRIXIVAN for free through the SUPPORT program.
 
Merck's co-pay assistance program
 
In addition to the SUPPORT Program, Merck has a co-pay assistance program in the U.S. for eligible patients on ISENTRESS who are commercially insured and have co-pays or coinsurance above $30, up to $400 per prescription. With this program, eligible patients can receive savings off their out-of-pocket costs for 12 prescriptions prior to the programs expiration in July 2011. Information about the co-pay assistance program can be obtained by calling 866-350-9232 or at www.isentress.com.   
 
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #123 on: May 17, 2010, 10:10:48 AM »
Testosterone Improves Metabolic Syndrome

MedPage Today
Published: May 15, 2010


PRAGUE -- Depot testosterone injections in men with metabolic syndrome and hypogonadism led to improvements in several important components of their disease, including significant weight loss and reduced glucose dysregulation, a researcher said here.

Action Points

Explain to interested patients that the testosterone product used in the study is not available or FDA approved in the U.S.


Explain that testosterone levels tend to be depressed in men with diabetes and the metabolic syndrome, but it is not yet proven that testosterone supplements are an effective treatment for these conditions.


Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
Interim results from a randomized, placebo-controlled trial showed that men receiving the hormone injections lost more than 4 kg (9 lb) in the first 30 weeks of a planned three-year study versus almost no change with placebo (P<0.001), reported Farid Saad, PhD, of Bayer Schering in Berlin.


Although fasting plasma glucose levels did not change, insulin levels dropped significantly among participants in the active treatment group, mainly among those with abnormally high levels at baseline, Saad told attendees here at the World Congress on Controversies to Consensus in Diabetes, Obesity, and Hypertension.


There were also trends toward normalized levels of certain blood lipids, serum leptin, and inflammation markers.


Many men with diabetes or metabolic syndrome show abnormally low testosterone levels, which has prompted several research groups and now the drug industry to investigate testosterone supplements as a therapy.


In March, for example, British researchers reported favorable results in diabetic and prediabetic men with a testosterone gel produced by a different company.


Bayer Schering has its own topical testosterone gel, with some results reported here as well, but the company is also interested in marketing its depot injectable version (Nebido) for this purpose. The product is currently approved outside the U.S. as a treatment for hypogonadism.


In the study Saad reported here, 184 men were randomized in a 3:2 ratio to the testosterone injection, at 1 g per dose, or placebo. Three injections were given, at weeks zero, six, and 18. Saad reported results of evaluations conducted at weeks 18 and 30.


Men receiving the hormone injections showed markedly greater decreases at week 30 in body mass index (BMI) and waist circumference as well as in body weight, according to Saad.


Mean BMI declined by 1.3 points from a baseline level of 36, compared with a 0.1-point decrease in the placebo group (P<0.001).


Similarly, waist circumference in the active treatment group shrank by 6 cm (2.5 inches) versus 1.5 cm (less than one inch) with placebo (P<0.001). Mean waist circumference at baseline was about 117 cm (46 inches).


Men in the placebo group lost about 0.3 kg compared with the 4-kg decline in the testosterone group (P<0.001).


Saad indicated that the weight loss was probably not a direct hormonal effect. Instead, he said, men on testosterone likely felt more energetic, exercising more and feeling motivated to eat a healthier diet.


Little to no change in fasting plasma glucose was noted during these first 30 weeks of treatment, Saad reported, but there was a significant decline in fasting insulin levels with the hormone treatment.


From a baseline value of about 26 mIU/L, insulin levels fell to 20. In the placebo group, mean levels increased slightly from 20.5 to 22 mIU/L (P=0.04 testosterone versus placebo).


Saad observed that the most substantial declines occurred in those patients with insulin levels above 26.4 mIU/L at baseline. The mean for those receiving the hormone dropped from 44 to 32 mIU/L (P=0.001), whereas there was almost no decline seen in patients with baseline insulin in the normal range.


The testosterone group showed nonsignificant trends toward reductions in LDL cholesterol (also seen with placebo) as well as increases in HDL levels. Mean serum leptin fell by nearly half (P<0.001) by week 30, with the 14.04-ng/mL level just above the normal range (upper limit, 13 ng/mL).


Saad also reported significant reductions in C-reactive protein and tumor necrosis factor-alpha levels in the treatment group, whereas increases or no change were seen in the control patients.


Session chair Robert Niecestro, PhD, managing director of the drug development firm Accelapharm in New York City, commented that the weight loss seen with the treatment was particularly impressive.
"I'll be interested to see if it persists for three years," he said.


Niecestro cautioned that these were early results from a planned three-year study. Consequently, some of the nonsignificant trends could become significant as the study progresses, or they could turn out to be temporary blips, he suggested.



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Re: http://natap.org/
« Reply #124 on: May 17, 2010, 10:11:20 AM »
Combo Treatment Effective in NASH

MedPage Today
Published: May 16, 2010

PRAGUE -- Adding the nutritional supplement alpha-lipoic acid to ursodeoxycholic acid (UDCA, ursodiol) reduced the major symptoms of non-alcoholic steatohepatitis (NASH) in a small controlled trial, it was reported here.

Action Points

Explain to interested patients that NASH is a serious complication of diabetes and obesity. FDA-approved treatments are available but many patients do not respond adequately.


Explain that it's important for patients to tell their doctors when they are taking so-called nutritional supplements, especially if they are also taking conventional prescription or over-the-counter medications.


Point out that this was a small study with a short follow-up period.


Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
Measures of fibrosis, liver transaminase levels, and overall disease severity were all improved significantly relative to diet-based treatment in a six-month, 20-patient study, according to Vincenzo Gianturco, MD, of the University of Rome "La Sapienza" in Italy.


UDCA is already an FDA-approved treatment for NASH, one of the major complications of diabetes and obesity, but many patients fail to show substantial improvement on the treatment.


Gianturco, speaking here at the World Congress on Controversies to Consensus in Diabetes, Obesity, and Hypertension, said about 2% to 3% of the population in Western countries suffers from NASH, an advanced stage of non-alcoholic fatty liver disease.


Both conditions are most common in middle-age, obese women with diabetes. However, according to Gianturco, NASH may be seen in individuals of any age or gender.


Alpha-lipoic acid is an antioxidant compound found naturally in human cells and in many foods -- and, in capsule form, in health food stores. It is used in complementary medicine to treat various diabetic complications and some neurologic conditions, on the theory that it has cytoprotective effects.


UDCA also appears to have cytoprotective effects, by a different mechanism; hence the idea to combine the two agents as a one-two punch against NASH.


Gianturco and colleagues randomly assigned 10 patients to receive ALAURSO -- 400 mg of alpha-lipoic acid plus 300 mg UDCA -- daily for six months. Ten other patients were randomized to a placebo group that was treated only with a low-calorie diet plan.


Patients with hepatitis B or C virus infection, alcohol drinkers, and those with gallbladder stones were excluded. Patients underwent liver biopsy at baseline, confirming the diagnosis, and again at the end of treatment.


Essentially no change in mean liver enzyme levels were seen in the control group, whereas the ALAURSO group showed substantial and statistically significant reductions (P=0.001) relative to controls, even with the small number of patients involved:
Aspartate acetyltransferase: baseline 47.0 mg/dL (SD 6.0); 30.6 mg/dL (SD 4.0) after treatment
Alanine acetyltransferase: baseline 50.9 mg/dL (SD 5.7); 33.4 mg/dL (SD 3.1) after treatment
Gamma-glutamyl acetyltransferase: baseline 57.7 mg/dL (SD 7.0); 34.2 (SD 3.5) after treatment
In the control group, none of the liver enzymes changed by more than 1 mg/dL with treatment.


Fibrosis scores increased in the control group, from 1.4 at baseline to 1.52, whereas scores declined significantly in the ALAURSO group, from 1.2 at baseline to 1.01 (P=0.04), Gianturco said.
Both compliance and tolerability were good, he told attendees here.


However, he cautioned that detailed histological analyses had not been performed. The small number of patients and the relatively short follow-up were also limitations, Gianturco said.


Session moderator Robert Niecestro, PhD, of the drug development firm Accelapharm in New York City, commented that alpha-lipoic acid is a chiral molecule, with both R- and S- enantiomers contained in commercially sold versions.


He said the R- enantiomer is responsible for the compound's beneficial effects, whereas the S- version tends to offset them somewhat.


Niecestro suggested that using only the R- form might further boost the effectiveness of the ALAURSO combination.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #125 on: May 17, 2010, 10:11:56 AM »
Latest Hepatitis C Figures Show Year On Year Increase, UK

New figures released by the Health Protection Agency (HPA) show reported cases of Hepatitis C infection in England to have increased by 4.5% from 8,196 cases reported in 2008 to 8,563 cases in 2009.

This year's figures released in advance of World Hepatitis Day bring the cumulative reported total (from 1992 to 2009) to 78,428 diagnosed cases.

There has been a steady increase in the number of laboratory confirmed diagnoses of hepatitis C infection since 1995. These gradual yearly increases indicate an increase in public awareness with more people coming forward to get tested. Healthcare campaigns by the Department of Health, the NHS and the voluntary sectors are all likely to have contributed to this increase in awareness over recent years.

Hepatitis is a condition characterised by inflammation of the liver and can be caused by the viral infections hepatitis A, B, C and E. Hepatitis C, is a blood-borne virus which if left untreated can eventually result in chronic liver disease, liver failure or death. Many individuals are unaware that they have become infected with the virus because signs and symptoms are rare in the early years of infection.

Currently, the greatest risk of contracting hepatitis C in the UK is through sharing equipment for injecting drugs. Sharing injecting equipment, even on a one-off basis, or a long time ago, could place an individual at risk of hepatitis C. Also, hepatitis C is more prevalent in the South Asian communities who have often acquired their infections via other routes. Others may have acquired their infections via blood transfusion in the UK more than two decades earlier, before the introduction of routine screening of blood for the virus in 1991.

There is currently no vaccine to protect against hepatitis C but simple measures such as using sterile injecting equipment and not sharing personal items like toothbrushes and razors will minimise your chances of being exposed to it.

Dr Mary Ramsay, Hepatitis expert at the Centre for Infections, at the HPA: "We must not get complacent about this, it is critical that awareness campaigns are sustained and enhanced if more people at risk of this infection are to be tested and treated."

"Liver disease is largely preventable and yet it continues to rise. The majority of hepatitis C infections can be treated successfully or prevented from occurring in the first place, yet new infections are continuing to occur and many existing infections remain undiagnosed"

"If people think they may have been exposed to the virus, they should contact their GP and request a test. Tackling undiagnosed hepatitis C infections by increasing awareness and encouraging people to come forward for testing could have a major impact on the number of people suffering needlessly from liver disease in the future."

The work of the HPA includes monitoring trends in hepatitis C at a national level and working with other agencies through a network of local leads to improve services for the prevention, diagnosis and treatment of hepatitis.


Source
Health Protection Agency

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #126 on: May 17, 2010, 10:12:59 AM »
1st International Workshop on HIV & Aging


4-5 October 2010, Baltimore, MD, USA
 
The  venue of the workshop is currently under deliberation.
If you would like to stay updated on the latest developments, please subscribe to our Newsletter: subscription form
Meer informatie
Link
More Information >>
Dear Colleagues,


It is our great pleasure to announce the 1st International Workshop on HIV & Aging, to be held in Baltimore, MD, USA, on 4-5 October 2010.

With an aging HIV-infected population - and suggestions that HIV itself may cause conditions normally associated with aging - there is a pressing need for more scientific dialog on this topic. This workshop will present a unique and much needed platform for international scientific exchange on the increasingly recognized problems of HIV and aging.
Progress in research and a large and increasing number of antiretrovirals have led to improved survival and quality-of-life for people living with HIV but aging patients today still face many challenges. Although some research is being performed on the effects of aging on HIV (and vice versa), no platform currently exists for the presentation and discussion of these data by cross-disciplinary experts in a small, focused scientific setting. We are convening the 1st International Workshop on HIV & Aging to address this objective.

The workshop will gather a cross-disciplinary team of  experts and trainees involved in HIV and aging research, in order to present and discuss the latest developments and strategies for the future, in an interactive and science - focused setting.

The meeting will have a two day program consisting of invited lectures, abstract-driven scientific presentations and poster sessions. The latest developments will be reviewed and evaluated in order to identify important topics for future research, develop better approaches to treatment, and create a strategic agenda for future management problems associated with HIV and aging.
The program will include important focus areas, such as: 
Neurology
Pharmacology
Metabolic complications
Immunology
Virology
Effects of aging on organ systems (renal, hepatic, endocrine, musculoskeletal)
Impact of human genetics on susceptibility to aging-related complications of HIV
Research / clinical trials
We invite you to attend the 1st International Workshop on HIV & Aging and encourage you to submit abstracts on your research in this field.
We hope to see you in Baltimore!
On behalf of the Organizing Committee,
Charles Flexner MD, Johns Hopkins University, USA 
Scott Letendre MD, UCSD, USA
Chairs 2010
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #127 on: May 18, 2010, 06:14:04 PM »
Generic 3TC+d4T Fixed Dose Tablets FDA Approved

On May 17, 2010, the Food and Drug Administration (FDA) granted tentative approval for lamivudine and stavudine Fixed Dose Combination tablets, 150mg/30mg, indicated in combination with other antiretrovirals for the treatment of HIV-1 infection in adults. This new fixed dose combination is manufactured by Hetero Drugs Limited, of Hyberdad, India.

FDA's tentative approval means that although a product meets all of the safety, efficacy, and manufacturing quality standards required for marketing in the U.S., existing patents and/or proprietary issues currently prevent marketing of the product in the United States. Tentative approval, however, does qualify the product for consideration for purchase under the President's Emergency Plan for AIDS Relief, or PEPFAR program.

As with all generic applications, FDA conducts an on-site inspection of the manufacturing facilities and of the facilities performing the bioequivalence studies prior to granting approval or tentative approval to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application.

These products were reviewed for PEPFAR under the FDA guidance titled Fixed Dose Combinations, Co-Packaged Drug Products, and Single-Entity Versions of Previously approved Antiretrovirals for the Treatment of HIV developed to clarify what regulatory requirements apply to such applications, what issues might be of concern, and how these issues should be addressed. The guidance is intended to encourage sponsors to submit applications for combination and co-packaged products, and to facilitate submission of such applications to FDA.

A list of all FDA approvals and tentative approvals for PEPFAR can be found on the FDA web site.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #128 on: May 18, 2010, 06:15:10 PM »
Decreased Kidney Function Predicts Death Risk in General Population

from Jules: in the general population kidney function declines with age and in HIV it does appear as though patients are in general experiencing accelerated aging or premature comorbidities. HIV+ individuals often have more risk factors for kidney dysfunction including a history of substance abuse, being African-American, diabetes (perhaps insulin resistance causes decline in kidney function), recent studies at conferences have been reported HIV+ individuals more often have proteinuria, an association between certain ARTs and kidney function, and HIV appears to be reswrvoired in the kidney. All suggesting that as the HIV patient population ages kidney function is likely to decline perhaps more than in the general population. Aging appears to be perhaps the number 1 concern for patients. Aging research has begiun to gain traction, the 1st Intl Aging/HIV Workshop is scheduled for Oct 2010 in Baltimore. We must get an understanding of how we can hopefull prevent premature and early onset for these comorbidities including besides kidnet disease - cardiovascular, diabetes, cancers, bone, the brain/CNS.

MedPage Today
Published: May 17, 2010

Two measures of impaired renal function are independent predictors of increased mortality risk among the general population, a meta-analysis showed.

Action Points

Explain to interested patients that this meta-analysis suggested that both estimated glomerular filtration rate and urinary albumin-to-creatinine ratio (ACR) may be useful in defining and staging chronic kidney disease.


This meta-analysis suggests, but does not establish a cause and effect, for increased mortality risk among individuals with a higher urine ACR and a reduced glomerular filtration rate.
Estimated glomerular filtration rates (eGFRs) of 60 mL/min/1.73 m2 or lower and urine albumin-to-creatinine ratios (ACR) of 1.1 or higher were associated with a greater risk of death in a pooled analysis of 21 studies, according to Josef Coresh, MD, PhD, of Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues from the International Chronic Kidney Disease Prognosis Consortium.


The findings are consistent with thresholds set by the Kidney Disease Outcomes Quality Initiative -- eGFR of 60 mL/min/1.73 m2 or less and albumin-to-creatinine ratio of 3.4 or higher -- for increased mortality, the researchers reported online in The Lancet.


In an accompanying editorial, Roberto Pontremoli, MD, PhD, of the University of Genoa in Italy, and colleagues, wrote, "Data from today's meta-analysis confirm beyond doubt that the current thresholds are indicative of increased all-cause and cardiovascular mortality risk."


The findings "will hopefully promote greater use of renal function tests in clinical practice aimed at global risk assessment," they said.


According to Coresh and his colleagues, there is continuing controversy around the use of eGFR and the presence of urinary albuminuria (protein in urine) to define chronic kidney disease and assign its stages.
They performed the meta-analysis to evaluate the associations of each measure -- both separately and combined -- with mortality in cohorts from the general population.


The analysis included 21 studies from Asia, Europe, North America, and Australia -- 14 with 105,872 total participants and urine albumin-to-creatinine ratio measurements and seven with 1,128,310 participants and urine protein dipstick measurements.


Through a median follow-up of 7.9 years, there were 45,584 deaths, including 9,637 from cardiovascular disease.


In the studies with ACR measurements, eGFRs between 75 and 105 mL/min/1.73 m2 were not significantly associated with mortality, but lower eGFRs were linked with a greater risk of death.


Compared with an eGFR of 95 mL/min/1.73 m2, the adjusted hazard ratios for all-cause mortality were 1.18 (95% CI 1.05 to 1.32) for 60 mL/min/1.73 m2, 1.57 (95% CI 1.39 to 1.78) for 45 mL/min/1.73 m2, and 3.14 (95% CI 2.39 to 4.13) for 15 mL/min/1.73 m2.


The hazard ratios tended to be higher in participants younger than 65 than in older patients, although tests for an interaction between eGFR and age did not reach statistical significance in most studies.


Urine albumin-to-creatinine ratio was associated with mortality in a linear fashion.


Compared with a ratio of 0.6 mg/mmol, the adjusted hazard ratios for all-cause mortality were 1.20 (95% CI 1.15 to 1.26) for 1.1 mg/mmol, 1.63 (95% CI 1.50 to 1.77) for 3.4 mg/mmol, and 2.22 (95% CI 1.97 to 2.51) for 33.9 mg/mmol.


All of the findings were similar in studies using dipstick measurements and when cardiovascular mortality was the outcome.


Both measures of reduced kidney function independently predicted mortality risk and, in most studies, did not have significant interactions with each other.


"In other words," the editorialists wrote, "knowing one's level of urine albumin excretion provides additional prognostic information for almost any given value of eGFR, and vice versa."


Coresh and his colleagues noted that the meta-analysis had several limitations:a lack of uniform study protocol and centralized analysis of laboratory results for all cohorts, and no standardized measurements for creatinine and albuminuria.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #129 on: May 19, 2010, 05:53:48 PM »
Bone Guidelines

Osteoporosis in Men
Apr 3, 2008 ... Guidelines The International Society for Clinical Densitometry recommends bone mineral density screening in men 70 years of age or older and ...
www.natap.org/2008/HIV/040708_01.htm
"These guidelines recommend bisphosphonates as first-line treatment for men in this age group whose bone mineral density is in the osteoporotic range, for men over the age of 50 years who have had fractures and have a T score below -1.5, and for men of any age who have osteopenia and have taken corticosteroids for 3 or more months or who have hypogonadism. Recent National Osteoporosis Foundation guidelines59 recommend pharmacologic therapy in men 50 years of age or older with hip or vertebral fractures; in men with a T score below -2.5; and in men with a T score between -1.0 and -2.5 with either a 10-year hip fracture probability of 3% or more or a total minimal trauma fracture probability of 20% or more."


Aging/HIV Clinical Care & Research - New IDSA Guidelines
New IDSA HIV Guidelines Push 'Adherence to Care' - (08/17/09) Bone Guidelines Excerpted From New IDSA Guidelines- pdf of full paper attached - (08/12/09) ...
www.natap.org/2009/HIV/082509_03.htm

"Baseline bone densitometry should be performed in postmenopausal women aged >65 years and in younger postmenopausal women with >1 additional risk factor(s) (other than being female and postmenopausal) for premature bone loss. Baseline bone densitometry should be considered in HIV-infected persons aged >50 years, especially if they have 1 risk factor(s) for premature bone loss. If the test demonstrates osteopenia or if the patient has a history of fragility or fracture, intervention with a bisphosphonate or other medical therapy should be considered"

CLINICIAN'S GUIDE TO PREVENTION AND TREATMENT OF OSTEOPOROSIS ...
NATIONAL OSTEOPOROSIS FOUNDATION http://www.nof.org. Since the NOF first published the guide in 1999, it has become increasingly clear that many patients ...
www.natap.org/2008/HIV/070708_01.htm

"In postmenopausal women and men age 50-70, recommend BMD testing when you have concern based on their risk factor profile......

Clinical Assessment of Osteoporosis in Postmenopausal Women and Men Age 50 and Older
-- Obtain a detailed patient history pertaining to clinical risk factors for osteoporosis-related fracture
-- Modify diet/supplements and other clinical risk factors for fracture
-- Estimate patient's 10-year probability of hip and any major
osteoporosis-related fracture using the
US-adapted WHO algorithm
-- Decisions on whom to treat and how to treat should be based on clinical judgment using this guide and all available clinical information
-- Consider FDA-approved medical therapies based on the following:
- A vertebral or hip fracture
- A DXA hip (femoral neck or total site) or spine T score ≦ -2.5
- Low bone mass and a U.S.-adapted WHO 10-yr probability of a hip fracture ≥ 3% or probability of any major osteoporosis-related fracture ≥ 20%
- Patient preferences may indicate treatment for people with 10-yr fracture probabilities below
these levels
-- Consider non-medical therapeutic interventions
- Modify risk factors related to falling
- Consider physical and occupational therapy including walking aids and hip pad protectors
- Weight-bearing activities daily
-- Patients not requiring medical therapies at the time of initial evaluation should be clinically reevaluated
when medically appropriate
-- Patients taking FDA-approved medications should have laboratory and bone density re-evaluation after two years or when medically appropriate"

Low Bone Mineral Density, Renal Dysfunction, and Fracture Risk in ...
Dec 1, 2009 ... Although the National US Osteoporosis Foundation does not recommend BMD screening for all patients with HIV, it explicitly states that ...
www.natap.org/2009/HIV/113009_01.htm

Men and Osteoporosis from the National Osteoporosis Foundation Today, 2 million American men have osteoporosis, and another 12 million are at risk for this disease. Yet, despite the large number of men affected, osteoporosis in men remains underdiagnosed and underreported.


Bone growth
During youth, bones grow in length and density. During the teen years, maximum height is reached, but bones continue to grow more dense until about age 30 when peak bone mass is attained. After that point, bones slowly start to lose density or strength. Throughout life, bone density is affected by heredity, diet, sex hormones, physical activity, lifestyle choices and the use of certain medications. Men have larger, stronger bones than women which explains, in part, why osteoporosis affects fewer men than women.


Risk factors for osteoporosis
The following risk factors are associated with osteoporosis in men:
Prolonged exposure to certain medications, such as steroids used to treat asthma or arthritis, anticonvulsants, certain cancer treatments and aluminum-containing antacids
Chronic disease that affects the kidneys, lungs, stomach and intestines and alters hormone levels
Undiagnosed low levels of the sex hormone testosterone
Lifestyle habits:
1. Smoking
2. Excessive alcohol use
3. Low calcium intake
4. Inadequate physical exercise
Age: Bone loss increases with age
Heredity
Race: Of all men, white men appear to be at greatest risk for osteoporosis. However, men from all ethnic groups develop osteoporosis
How is osteoporosis diagnosed?
Unfortunately, the diagnosis of osteoporosis in men is often overlooked. Your physician may take a medical history to identify risk factors and conduct a complete physical exam, in bone mineral density test (BMD Test), a special type of x-ray that can diagnose osteoporosis.


If you notice a loss of height, change in posture or sudden back pain, it is important to inform your doctor.


How can osteoporosis in men be prevented and treated?
Experts agree that all persons should take the following steps to preserve bone health.
Recognize and treat any underlying medical conditions that affect bone health. Identify and evaluate the use of medications that are known to cause bone loss.
Change unhealthy habits, such as smoking, excessive alcohol intake, and inactivity.
Make sure to get enough calcium each day to keep bones healthy.  Men under age 50 need 1,000 mg of calcium daily, and men age 50 and over need 1,200 mg of calcium daily.
Make sure to get adequate vitamin D.  Men under age 50 need 400-800 IU of vitamin D daily, and men age 50 and over need 800-1,000 IU of vitamin D daily.
Engage in a regular regimen of weight-bearing exercises where bone and muscles work against gravity. This includes walking, jogging, racquet sports, stair climbing and team sports. Also, lifting weights or using resistance machines appears to help preserve bone density. Exercise also improves balance and muscle tone and imparts a sense of well-being. If you have already been diagnosed with osteoporosis, any exercise program should be evaluated for safety by your doctor before you begin. Twisting motions and impact activities may need to be curtailed depending on the severity of your condition.
What medications can slow or stop bone loss in men?
Medications to treat osteoporosis fall into two main categories:  antiresorptives and anabolics. Antiresorptives slow bone loss. The Food and Drug Administration (FDA) has approved three antiresorptive medications to treat osteoporosis in men.  These are alendronate (brand name Fosamax?), risedronate (brand name Actonel?) and zoledronic acid (brand name Reclast?). These medications are in a class of drugs called bisphosphonates.



Anabolics speed up bone formation. Only one anabolic medication has been approved to treat osteoporosis. This medication is teriparatide (brand name Forteo?), and it is approved for men. This medication is in a class of drugs called parathyroid hormone.



Testosterone helps protect the bones of men.  When osteoporosis is due to low testosterone levels, testosterone replacement therapy may be a treatment option.


New members of the NOF family receive our quarterly newsletter, Osteoporosis Report, and a copy of our newly revised, 100+ page handbook, Boning Up on Osteoporosis. Renewing members receive NOF's quarterly newsletter.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #130 on: May 20, 2010, 06:33:38 AM »
When it Comes to Sparking a Woman?s Sexual Desire, Most Men ? and Even Women ? May Not Know Where to Start
- Actress Lisa Rinna kicks off campaign highlighting connection between brain, body and sexual desire -


Washington, D.C., May 12, 2010 ?When it comes to sex, more than half of men and women don?t recognize the brain as an important female sexual organ, according to a new survey.*
?The root of a woman?s desire is complex, but it is thought to start with her brain.  The brain is the center for thoughts and emotions, but it is also home to a complex system of nerves, hormones and other chemicals that can affect sexual desire,? said Laura Berman, LCSW, Ph.D., and sex and relationship expert.



Interestingly, the survey revealed that women and men?s feelings about sex and sexual desire are more alike than people may think, as they both agree that sexual health is important for a woman?s overall health and well being.  Yet, while most women surveyed would be concerned if they experienced, and most men would be concerned if their partner experienced, a decrease in sexual desire, less than half of both women and men have ever discussed these issues with their partner.


Today, the Society for Women?s Health Research (SWHR), along with actress and TV personality Lisa Rinna, launched ?Sex Brain Body: Make the Connection,? a new educational campaign about female sexual health, particularly about the role the brain is thought to play in female sexual desire.



?As a woman, wife and mother, I know that women?s sexual desire can fluctuate.  For some women that?s normal, but for others it may be something more,? Rinna said.  ?Everyone is entitled to a healthy sex life.  That?s why I?m encouraging women to learn more about their sexual health and the brain?s potential role in desire, so they can talk more openly about it with a partner and health care provider.  By visiting www.SexBrainBody.com, I want to empower women to learn more about their sexual health and better understand sexual desire.?   



Experts believe that chemicals in the brain may play a role in sexual response, impacting a woman?s sexual desire.  Women and men surveyed believe that desire is important for a healthy sex life, and that a decline in a woman?s desire would be distressing to the woman.  Yet, few people realize that a lack of sexual desire accompanied by distress might be something more than stress from a demanding career or family commitments.  It may be a medical condition known as Hypoactive Sexual Desire Disorder, or HSDD.


By visiting www.SexBrainBody.com, women can learn more about HSDD, as well as find helpful tips for starting what may be an uncomfortable conversation with their partners or health care providers about their sexual health and any issues they may be experiencing.



?For 20 years, SWHR has provided resources and knowledge to empower women to take control of their health.  We are proud to be supporting this campaign to help women understand their sexual health and give them the confidence to discuss their needs,? said Phyllis E. Greenberger, M.S.W., President and CEO of SWHR in Washington, D.C.


Survey Findings
The ?Sex Brain Body: Make the Connection? survey included 1,300 women ages 30 to 55 years and 1,129 men ages 30 to 65 years.  The survey was designed to explore the attitudes and behaviors of women regarding their sexual health, as well as men?s perception of a woman?s sexual health.



Highlights of the survey include the following:


Nearly 75 percent of women report experiencing a lack of sexual desire at least occasionally, with 20 percent reporting a lack of desire frequently
Both women and men believe a woman?s lack of desire for sex would cause distress in a relationship (78 percent women, 63 percent men); more than half of women and men say that a lack of desire would have a negative impact on their relationship
Most women (roughly 60 percent) say they would discuss low sexual desire with their health care provider, yet only 14 percent have actually done so
More women would rather discuss other health topics such as allergies, skin care, hair loss and weight issues with their health care provider than talk about their sexual health
Women are seven times more familiar with erectile dysfunction (66 percent) than Hypoactive Sexual Desire Disorder (HSDD) (9 percent)


About ?Sex Brain Body: Make the Connection?
?Sex Brain Body: Make the Connection? is an educational campaign meant to help women recognize the potential links between the brain, the body and sexual desire, so they can better understand and address their own sexual health.  The campaign is sponsored by the Society for Women?s Health Research and content was developed with the support of a sponsorship from Boehringer Ingelheim Pharmaceuticals, Inc.  To learn more about the sex-brain-body connection, visit www.SexBrainBody.com.


Low sexual desire is the most commonly reported female sexual complaint.  Approximately one in 10 women reported low sexual desire with associated distress, which may be HSDD.  HSDD is a form of female sexual dysfunction (FSD) and has been recognized as a medical condition for more than 30 years.  As defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), HSDD is the persistent or recurrent lack (or absence) of sexual fantasies or desire for any form of sexual activity causing marked distress or interpersonal difficulty and not better accounted for by another disorder (except another sexual dysfunction), direct physiological effects of a substance (including medications), or a general medical or psychiatric condition.  Generalized, acquired HSDD is not limited to certain types of stimulation, situations or partners, and develops only after a period of normal functioning.  There has been an unmet need for women as there is no FDA-approved treatment for HSDD.  It can affect women of all ages and at any stage of life.


*About the Survey
A demographically representative national internet sample of 1,300 women between the ages of 30 and 55 and 1,129 men 30-65 were invited via email to participate in a 10-minute self-administered online survey.  Women meeting any of the following criteria were eliminated from participating: had a full hysterectomy, currently take hormone replacement therapy, are post-menopausal and have already gone through menopause.  The surveys were administered between February 8 and March 18, 2010.  Data for these studies are tested for statistical difference at a confidence level of 95 percent.  Data are weighted to reflect accurate representation of population.


About Society for Women?s Health Research
The Society for Women?s Health Research (SWHR), a national non-profit organization based in Washington, D.C., is widely recognized as the thought leader in research on sex differences and is dedicated to improving women?s health through advocacy, education, and research.  SWHR was founded in 1990 by a group of physicians, medical researchers and health advocates who wanted to bring attention to the myriad of diseases and conditions that affect women uniquely.  Women?s health, until then, had been defined primarily as reproductive health.  Women were not routinely included in most major medical research studies and scientists rarely considered biological sex as a variable in their research.


About GfK Healthcare
GfK Healthcare (www.gfkhc.com) is the largest provider of fully integrated custom health care marketing research in the United States. With the broadest range of custom, syndicated and proprietary research offerings, paired with expertise in managed markets and sales force effectiveness, GfK Healthcare is equipped to meet a product?s needs across its life cycle, through flexible marketing research resources, responsive to clients? evolving challenges. GfK Healthcare is part of the GfK Group.


About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.


The Boehringer Ingelheim group is one of the world?s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.


In 2009, Boehringer Ingelheim posted net sales of US $17.7 billion (12.7 billion euro) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #131 on: May 20, 2010, 06:34:31 AM »
Boehringer Ingelheim Sexual Drive Drug For Women in Clinical Trials

http://www.femininereview.com

Girosa or Flibanserin?
Girosa is supposed proposed name given to the Flibanserin drug under clinical trials by Boehringer Ingelheim. There is a lot of secrecy shrouding the product line and not much information can be found and for good reason. It is estimated that the market for the sometime called female Viagra is valued at around $30 million dollars a year in sales. The product has been under development and trials for several years now and the name has typically been known as Flibanserin but there is knowledge that Girosa will be the official product name if it is approved for use in the United States.
What is it?
Girosa is actually a non-hormonal drug made up from dopamine or D4 receptors and serotonin receptors known as 5-HT. Ironically it was first researched to become an antidepressant but our guesses are that as soon as improvements in female libido were recognized the company saw that there would be more profit in this area than the over flooded mood enhancer arena. Basically, it is a drug that raises dopamine in the female body. Dopamine is partially responsible for sexual desire and arousal and therefore this drug may have the ability to help with pre-menopausal Hypo Sexual Desire Disorder or Female Sexual Dysfunction. At least, that's the target market and goal for the end product.
Ironically Boehringer Ingelheim is not completely sure how the positive impact on sexual health occurs from Flibanserin but they are seeing positive results during all of their 4 clinical trials that have included over 5,000 women located in over 220 clinics worldwide. Just like BioSante is aiming to get LibiGel approved by the FDA in the next 18 months Boehringer is hoping to have an FDA approval for US medical use in 2009. Aiming at the Viagra market but for women it is easy to see how a billion dollar industry for men can have a trickle effect into the women's market being that scientists and doctors currently estimate 40% of all women in the US suffer from some symptom of FSD or HSDD.
Can I buy Girosa?
Currently the race is on to make a product available for women suffering from lower libido or any of the ailments associated with decreased sexual activity. However, there currently is not a legal option for women in the United States. This drug looks very promising as the clinical trials have been under development for quite some time. We will commit to keeping our readers up to date with the most recent information on Flibanserin.
Tell me about these clinical trials
The German bio pharmaceutical firm Boehringer Ingelheim has been sponsoring clinical studies to research the ability for Girosa (Flibanserin) to aid in women suffering from HSDD or FSD. The studies are taking place in over 350 locations around the world including the US, Europe, and Canada and more than 5,000 women have partaken in the study or trials.
During the clinical trials, it has been noted that the number one coprimary endpoint of mean desire in a month stabilised at about 9 months at an approximate 4.5 decrease from the randomized baseline of 34.2. By just under 9 months. This was a significant improvement over the group administered a placebo which stabilised much later around 11 months and showed a lesser decrease of approximately 8.5 percent decrease.
The second study which basically measured the amount of satisfying sexual events per month has shown some pretty clear results in a positive side for Girosa compared to the measured placebo group and at a much quicker rate as well.
Are there any known side effects yet?
As with any medication there are bound to be side effects found and established. The body simply does not agree with every type of therapy and every person reacts differently. While this is not an FDA approved product yet and all information is preliminary there have been some Girosa side effects mentioned including:
Fatigue or Tiredness
Headaches
Some Dizziness
Nausea or General Sickness
Rare cases of Urinary Infections
Sinusitis
Some cases of Diarrhea
These don't appear to be extremely adverse effects related to the drug and the results that it could promise may be well worth the risks.
What about now?
Well, as we always mention you should probably talk to your doctor about all available therapies and treatments that can help with symptoms you may be experiencing. There are plenty of natural resources available on the market and you can browse through our review section to see what women have been saying about some of the products like Lyriana and Provestra which both are getting pretty decent reviews that appear to be backing up the product manufacturers claims. We will be sure to let everybody know the latest info on Girosa though.
----------------------




Boehringer Ingelheim announces new data on flibanserin in pre-menopausal women with HSDD
New analyses from pivotal Phase III flibanserin trials presented today
http://www.eurekalert.org



Ridgefield, CT, May 18, 2010 ? Data from pivotal Phase III clinical trials demonstrate that a higher proportion of pre-menopausal women with Hypoactive Sexual Desire Disorder (HSDD) receiving flibanserin 100mg reported both an improvement in their condition and a meaningful benefit from their treatment, compared to placebo. Flibanserin is an investigational compound being developed by Boehringer Ingelheim Pharmaceuticals, Inc. for the treatment of HSDD in pre-menopausal women. HSDD is a persistent or recurrent decrease or lack of sexual desire that causes distress for the patient, may put a strain on relationships with partners, and is not due to the effects of a substance, including medications, or another medical condition.


The findings, presented at the 58th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists in San Francisco, include data from a pre-specified pooled analysis of two pivotal North American trials (DAISY? and VIOLET?) assessing flibanserin 100mg in pre-menopausal women suffering from HSDD.


"These new data offer a unique perspective on the effects of flibanserin 100 mg from the patient's point of view. Not only did pre-menopausal women with HSDD report feeling an improvement in their symptoms of low desire and associated distress when taking flibanserin, but they also reported that this change had a meaningful benefit to them," said John Thorp, MD, study investigator, Professor of Obstetrics and Gynecology, University of North Carolina Medical School.


These findings add to data from the primary and secondary endpoint analysis of flibanserin pivotal trials. According to the pre-specified pooled analysis of women who completed 24 weeks of treatment, flibanserin 100mg showed statistically significant improved measures of sexual desire, overall sexual functioning, distress associated with low sexual desire, and the number of satisfying sexual events (SSE), compared with placebo.


"HSDD is an under-recognized and often misunderstood condition that can take a toll on women," said Peter Piliero, MD, executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We are committed to advancing flibanserin's development to help understand and find a treatment for women affected by this distressing medical condition."


North American Phase III Trial Results


Patient Perspective Analysis
The pooled analysis included 1,378 pre-menopausal women with HSDD treated with either flibanserin 100 mg or placebo for 24 weeks. The women evaluated their overall improvement in "bothersome decreased sexual desire" using the Patient's Global Impression of Improvement (PGI-I), which is a 7-point scale from 1 (very much improved) through 4 (no change) to 7 (very much worse). By 24 weeks, 48.3 percent of women receiving flibanserin and 30.3 percent of women receiving placebo reported feeling very much improved, much improved or minimally improved (p<0.0001).


In addition, more women in the flibanserin group versus placebo reported experiencing a meaningful benefit from the study medication (40.5 percent versus 25.2 percent, respectively; p < 0.0001), using a single-question Patient Benefit Evaluation (Overall, do you believe that you have experienced a meaningful benefit from the study medication?).


Analysis of Completers
The pooled analysis included 971 (flibanserin 100 mg qhs: 450; placebo: 521) pre-menopausal women who completed the 24-week trials. In that analysis, flibanserin 100mg significantly increased the frequency of SSE versus placebo (increase of 2.1 events vs. 0.9 events, respectively; p < 0.0001) over the 24-week study period. The analysis also found that, compared with placebo, flibanserin 100 mg showed statically significant improved measures of sexual desire using an electronic daily diary or eDiary (primary endpoint) and on the Female Sexual Function Index (FSFI) desire domain (secondary endpoint). Compared with placebo, flibanserin also showed statistically significant improved sexual functioning (as measured by the FSFI total score), and distress related to low sexual desire (based on the Female Sexual Distress Scale-Revised, FSDS-R, total score), which were secondary endpoints.


The FSFI and FSDS-R desire scores are independently developed and validated tools that provide additional measurement of changes in desire over a four-week recall period. The FSFI is a 19-item self-administered questionnaire composed of six domains (desire, arousal, lubrication, orgasm, satisfaction, and pain). The FSDS-R is a 13-item self-administered questionnaire. The total score ranges from zero to 52, with the higher scores indicating more sexual distress.


Pivotal Trials Safety Data
The most commonly reported adverse events (AEs) with flibanserin 100mg in the pivotal North American trials were mild to moderate and emerged during the first 14 days of treatment. These AEs reported by more women on flibanserin than on placebo included somnolence (daytime sleepiness), dizziness, fatigue, anxiety, dry mouth, nausea and insomnia. The majority of these AEs resolved with continued treatment. About 15 percent of women on flibanserin 100mg and seven percent of women on placebo discontinued treatment due to AEs.


###


About Flibanserin
Flibanserin is an investigational compound being developed by Boehringer Ingelheim for the treatment of HSDD in pre-menopausal women. Pooled data from pivotal phase III trials demonstrated that flibanserin 100mg increased the number of satisfying sexual events (SSE) and sexual desire while decreasing the distress associated with HSDD. The most commonly reported adverse events (AEs) with flibanserin 100mg were mild to moderate and emerged during the first 14 days of treatment. These AEs reported by more women on flibanserin than on placebo included somnolence (daytime sleepiness), dizziness, fatigue, anxiety, dry mouth, nausea and insomnia. The majority of these AEs resolved with continued treatment. About 15 percent of women on flibanserin 100mg and seven percent of women on placebo discontinued treatment due to AEs.


About Hypoactive Sexual Desire Disorder
Low sexual desire is the most commonly reported female sexual complaint. Approximately one in 10 women report low sexual desire with associated distress, which may be HSDD. HSDD is a form of female sexual dysfunction (FSD) and has been recognized as a medical condition for more than 30 years. As defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), HSDD is the persistent or recurrent lack (or absence) of sexual fantasies or desire for any form of sexual activity causing marked distress or interpersonal difficulty and not better accounted for by another disorder (except another sexual dysfunction), direct physiological effects of a substance (including medications), or a general medical or psychiatric condition. Generalized, acquired HSDD is not limited to certain types of stimulation, situations or partners, and develops only after a period of normal functioning. There is an unmet need for women as there is no FDA-approved treatment for HSDD. It can affect women of all ages and at any stage of life.


Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.


The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.


In 2009, Boehringer Ingelheim posted net sales of US $17.7 billion (12.7 billion euro) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.


For more information, please visit http://us.boehringer-ingelheim.com
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

“Neither look forward where there is doubt nor backward where there is regret. Look inward and ask not if there is anything o

Offline red_Dragon888

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Re: http://natap.org/
« Reply #132 on: May 20, 2010, 06:35:23 AM »
Boehringer?s sexual desire drug for women hits the spot

19 May 2010
pharmatimes.com

Boehringer Ingelheim has posted interesting late-stage data for its female sexual dysfunctional drug flibanserin which suggests that the treatment increases satisfaction.

Data from two Phase III trials run in North America were presented at the American College of Obstetricians and Gynaecologists annual meeting in San Francisco. They demonstrate that a higher proportion of pre-menopausal women with hypoactive sexual desire disorder receiving flibanserin 100mg ?reported both an improvement in their condition and a meaningful benefit from their treatment, compared to placebo?.

The analysis included 1,378 pre-menopausal women with HSDD who were evaluated about "bothersome decreased sexual desire" using a seven-point scale from 1 (very much improved) through 4 (no change) to 7 (very much worse). After 24 weeks, 48.3% of women receiving flibanserin and 30.3% on placebo reported feeling very much improved, much improved or minimally improved . In addition, more women on the Boehringer drug reported experiencing a meaningful benefit from the study medication (40.5% versus 25.2%).

Study investigator John Thorp of the University of North Carolina Medical School said the data ?offer a unique perspective on the effects of flibanserin from the patient's point of view?. Not only did the women feel an improvement ?in their symptoms of low desire and associated distress when taking flibanserin, but they also reported that this change had a meaningful benefit to them?.

These latest findings add to data from other pivotal trials which have shown that flibanserin demonstrated statistically significant improved measures of sexual desire, overall sexual functioning, distress associated with the condition and the number of satisfying sexual events, compared with placebo.

Flibanserin, an oral treatment that was originally developed as an antidepressant, affects levels of serotonin and other chemicals in the brain but how it affects sex drive remains unclear. In mid-June, an advisory panel of the US Food and Drug Administration will vote on whether to recommend approval.

Given the nature of HSDD, it is unsurprising that flibanserin is being referred to in some media circles as ?female Viagra?. However, Paula Hall, a sexual and relationship psychotherapist from the UK, said that although HSDD affects thousands of women, ?it is often misunderstood or overlooked?. She added that in both of these study analyses, ?we?re seeing very positive outcomes with flibanserin, which is really quite exciting and could hold hope for those suffering with this distressing condition.?
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #133 on: May 20, 2010, 06:37:53 AM »
press announcement

Boehringer Ingelheim Announces New Data on Flibanserin in Pre-Menopausal Women with Hypoactive Sexual Desire Disorder
- New analyses from pivotal Phase III flibanserin trials presented today -


Ridgefield, CT, May 18, 2010 ?Data from pivotal Phase III clinical trials demonstrate that a higher proportion of pre-menopausal women with Hypoactive Sexual Desire Disorder (HSDD) receiving flibanserin 100mg reported both an improvement in their condition and a meaningful benefit from their treatment, compared to placebo.  Flibanserin is an investigational compound being developed by Boehringer Ingelheim Pharmaceuticals, Inc. for the treatment of HSDD in pre-menopausal women.  HSDD is a persistent or recurrent decrease or lack of sexual desire that causes distress for the patient, may put a strain on relationships with partners, and is not due to the effects of a substance, including medications, or another medical condition.


The findings, presented at the 58th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists in San Francisco, include data from a pre-specified pooled analysis of two pivotal North American trials (DAISY? and VIOLET?) assessing flibanserin 100mg in pre-menopausal women suffering from HSDD.



?These new data offer a unique perspective on the effects of flibanserin 100 mg from the patient?s point of view.  Not only did pre-menopausal women with HSDD report feeling an improvement in their symptoms of low desire and associated distress when taking flibanserin, but they also reported that this change had a meaningful benefit to them,? said John Thorp, MD, study investigator, Professor of Obstetrics and Gynecology, University of North Carolina Medical School.


These findings add to data from the primary and secondary endpoint analysis of flibanserin pivotal trials.  According to the pre-specified pooled analysis of women who completed 24 weeks of treatment, flibanserin 100mg showed statistically significant improved measures of sexual desire, overall sexual functioning, distress associated with low sexual desire, and the number of satisfying sexual events (SSE), compared with placebo.


?HSDD is an under-recognized and often misunderstood condition that can take a toll on women,? said Peter Piliero, MD, executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.  ?We are committed to advancing flibanserin?s development to help understand and find a treatment for women affected by this distressing medical condition.?


North American Phase III Trial Results


Patient Perspective Analysis

The pooled analysis included 1,378 pre-menopausal women with HSDD treated with either flibanserin 100 mg or placebo for 24 weeks.  The women evaluated their overall improvement in ?bothersome decreased sexual desire? using the Patient?s Global Impression of Improvement (PGI-I), which is a 7-point scale from 1 (very much improved) through 4 (no change) to 7 (very much worse).  By 24 weeks, 48.3 percent of women receiving flibanserin and 30.3 percent of women receiving placebo reported feeling very much improved, much improved or minimally improved (p<0.0001).



In addition, more women in the flibanserin group versus placebo reported experiencing a meaningful benefit from the study medication (40.5 percent versus 25.2 percent, respectively; p<0.0001), using a single-question Patient Benefit Evaluation (Overall, do you believe that you have experienced a meaningful benefit from the study medication?).


Analysis of Completers

The pooled analysis included 971 (flibanserin 100 mg qhs: 450; placebo: 521) pre-menopausal women who completed the 24-week trials.  In that analysis, flibanserin 100mg significantly increased the frequency of SSE versus placebo (increase of 2.1 events vs. 0.9 events, respectively; p<0.0001) over the 24-week study period.  The analysis also found that, compared with placebo, flibanserin 100 mg showed statically significant improved measures of sexual desire using an electronic daily diary or eDiary (primary endpoint) and on the Female Sexual Function Index (FSFI) desire domain (secondary endpoint).  Compared with placebo, flibanserin also showed statistically significant improved sexual functioning (as measured by the FSFI total score), and distress related to low sexual desire (based on the Female Sexual Distress Scale-Revised, FSDS-R, total score), which were secondary endpoints.


The FSFI and FSDS-R desire scores are independently developed and validated tools that provide additional measurement of changes in desire over a four-week recall period.  The FSFI is a 19-item self-administered questionnaire composed of six domains (desire, arousal, lubrication, orgasm, satisfaction, and pain).  The FSDS-R is a 13-item self-administered questionnaire.  The total score ranges from zero to 52, with the higher scores indicating more sexual distress.



Pivotal Trials Safety Data

The most commonly reported adverse events (AEs) with flibanserin 100mg in the pivotal North American trials were mild to moderate and emerged during the first 14 days of treatment.  These AEs reported by more women on flibanserin than on placebo included somnolence (daytime sleepiness), dizziness, fatigue, anxiety, dry mouth, nausea and insomnia.  The majority of these AEs resolved with continued treatment.  About 15 percent of women on flibanserin 100mg and seven percent of women on placebo discontinued treatment due to AEs. 



About Flibanserin
Flibanserin is an investigational compound being developed by Boehringer Ingelheim for the treatment of HSDD in pre-menopausal women.  Pooled data from pivotal phase III trials demonstrated that flibanserin 100mg increased the number of satisfying sexual events (SSE) and sexual desire while decreasing the distress associated with HSDD.  The most commonly reported adverse events (AEs) with flibanserin 100mg were mild to moderate and emerged during the first 14 days of treatment.  These AEs reported by more women on flibanserin than on placebo included somnolence (daytime sleepiness), dizziness, fatigue, anxiety, dry mouth, nausea and insomnia.  The majority of these AEs resolved with continued treatment.  About 15 percent of women on flibanserin 100mg and seven percent of women on placebo discontinued treatment due to AEs.   



About Hypoactive Sexual Desire Disorder
Low sexual desire is the most commonly reported female sexual complaint.  Approximately one in 10 women report low sexual desire with associated distress, which may be HSDD.  HSDD is a form of female sexual dysfunction (FSD) and has been recognized as a medical condition for more than 30 years.  As defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), HSDD is the persistent or recurrent lack (or absence) of sexual fantasies or desire for any form of sexual activity causing marked distress or interpersonal difficulty and not better accounted for by another disorder (except another sexual dysfunction), direct physiological effects of a substance (including medications), or a general medical or psychiatric condition.  Generalized, acquired HSDD is not limited to certain types of stimulation, situations or partners, and develops only after a period of normal functioning.  There is an unmet need for women as there is no FDA-approved treatment for HSDD.  It can affect women of all ages and at any stage of life.


About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.


The Boehringer Ingelheim group is one of the world?s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of US $17.7 billion (12.7 billion euro) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.


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Offline red_Dragon888

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Re: http://natap.org/
« Reply #134 on: May 23, 2010, 11:28:04 AM »
New Aging/HIV Study: Study pinpoints how a normally defensive immune response can help HIV



May 19, 2010

http://news.ucsf.edu






Researchers have identified how a normal response to infection, one that usually serves to limit the amount of inflammation, actually contributes to disease progression and viral persistence in HIV-infected patients.




The findings, published in the May 19 issue of the journal Science Translational Medicine, offer important opportunities for further research, both for treatment of long-term persistence of HIV in those who are infected and for prevention of infection in those who are not, according to the study team.




The study, led by UCSF researchers, focused on the body?s production of an enzyme called indoleamine 2,3-dioxygenase 1 (IDO1). To prevent the harm associated with chronic inflammation, the body typically turns on IDO1, which then serves to suppress inflammation and immune responses. In the setting of HIV infection, the authors found that IDO1 instead acts to alter the balance between two types of T-cells that have opposing functions.




One type of immune cell, called TH17, releases interleukin-17, a cytokine that has a central role in maintaining the integrity of the mucosal barrier in the gut. The other type, named Treg, prevents inflammation in a non-specific manner and can also turn off immune responses against viruses such as HIV.




The authors found that induction of IDO1 by HIV results in loss of TH17 cells and a relative increase in Tregs. This change in the balance of TH17 cells and Tregs allows bacteria to cross the mucosal barrier of the gut, initiating new inflammatory reactions in the process. At the same time, the increased number of Tregs may prevent the immune system from attacking HIV in areas of the body where strong HIV-specific immune responses are most needed. The altered TH17/Treg balance, in sum, leads to an endless cycle of inflammation induced by the invading microbes, more induction of IDO1, and continued loss of TH17 cells.




?In most instances, reducing inflammation following immune system activation to fight infection is beneficial.  But, in HIV disease, this can establish a reinforcing cycle that is strongly linked to disease progression and that may help HIV to persist in patients, said study lead co-author, Jeff Mold, PhD, from the UCSF Division of Experimental Medicine.  ?Mucosal defenses are breached, microbes cross over, and inflammation results. This leads to increasing IDO1 activity, continued changes in the balance of TH17 and Treg cells, further weakening of the mucosal defenses, and even more inflammation.?




The findings represent the next step in a series of research studies reported previously by the same group of investigators, showing that SIV infection of monkeys leading to AIDS is associated with a similar change in TH17 and Treg balances.  The change in T cell balance was not observed in another primate, African green monkeys, where infection with SIV is harmless and does not cause disease.




In the current study, the investigators looked at IDO1 activity in HIV-infected human subjects at various stages of disease and in healthy non-infected subjects.




?We confirmed that IDO1 activity is associated with HIV disease progression.  But we went further and also looked at the TH17 and Treg balance, and found that the change in the ratio leading to decreasing TH17 cells is also associated with HIV disease progression,? said study lead co-author, David Favre, PhD, formerly at UCSF, now with the National Immune Monitoring Laboratory, Montreal.




With pharmacological inhibitors of IDO1 in development and currently in clinical trials for cancer immunotherapy, the finding may lead to new therapeutic approaches for assisting in the control of HIV disease, noted the study team.




?Most of an infected person?s own immune responses that are known to affect HIV disease outcomes cannot be manipulated or altered clinically and, hence, have not really had much of an impact for patients. This work, however, is very different, as it has uncovered several possible pathways that might be addressed clinically with developing or available therapeutics,? said study co-author, Steven Deeks, MD, professor of medicine at the UCSF Division of HIV/AIDS at San Francisco General Hospital.




IDO1 may play a role in the ability of HIV to persist in HIV-infected patients for their lifetimes, notwithstanding effective treatment with antiretroviral therapies.




?Steve Deeks and I are continuing to examine the role of IDO1 through a study recently announced by amfAR, the Foundation for AIDS Research, into whether the disruption of IDO1 will reduce the level of immune activation, which could then lead to a decrease in viral persistence,? said senior study author Joseph M. McCune, MD, PhD, chief of the UCSF Division of Experimental Medicine.




In addition to Favre, Mold, Deeks, and McCune, other study co-authors include Peter Hunt, Bittoo Kanwar, Lillian Seu, Jason Barbour, Margaret Lowe, Anura Jayawardene, Francesca Aweeka, Yong Huang, Jeffrey Martin, and Frederick Hecht from UCSF; Daniel Douek and Jason Brenchley from the National Institute of Allergy and Infectious Diseases, NIH, and P?ng Loke from NYU.




The research was funded by grants from the Elizabeth Glaser Pediatric AIDS Foundation, the National Institute of Allergy and Infectious Diseases, the National Institutes for Health, the Harvey V. Berneking Living Trust, the UCSF-GIVI Center for AIDS Research, and the UCSF Clinical and Translational Institute Clinical Research Center.




The UCSF Division of Experimental Medicine and the UCSF Division of HIV/AIDS at SFGH are affiliated with the AIDS Research Institute (ARI) at UCSF.  UCSF ARI houses hundreds of scientists and dozens of programs throughout UCSF and affiliated labs and institutions, making ARI one of the largest AIDS research entities in the world.




UCSF is a leading university dedicated to defining health worldwide through advanced biomedical research, graduate level education in the life sciences and health professions, and excellence in patient care.

------------------


 Sci Transl Med  19 May 2010:

Vol. 2, Issue 32, p. 32ps23



    COMMENTARY




Insights into Therapy: Tryptophan Oxidation and HIV Infection




   Michael F. Murray

 Department of Medicine, Brigham and Women?s Hospital, Boston, MA 02115, USA.

E-mail: mmurray@partners.org




Abstract




New data from Favre and colleagues strengthen the link between activation of the tryptophan oxidation (TOx) pathway?via the indoleamine 2,3-dioxygenase enzymes IDO1 and IDO2?and chronic inflammation in progressive HIV disease. It can now be appreciated that a pathogenic TOx activation cycle exists in HIV. TOx regulation is a therapeutic target for other diseases, such as cancer and autoimmune disorders. Here TOx control is examined with an eye to eventual therapeutic intervention in HIV disease.






HIV AND BEYOND




Microbial products, including lipopolysaccharide (LPS), the immunostimulatory endotoxin from the outer membrane of Gram-negative bacteria, are known to induce the tryptophan oxidation (TOx) pathway, which is the key degradation route for the essential amino acid l-tryptophan (l-Trp). The first (and rate-limiting) step in the pathway?the conversion of l-Trp to N-formyl-kynurenine?is catalyzed by the indoleamine 2,3-dioxygenases IDO1 and IDO2, two enzymes that are synthesized in both immune cells and other tissues and are the gatekeepers of the immune response via the TOx pathway. In this issue of Science Translational Medicine, Favre and colleagues add to a growing body of knowledge linking LPS-induced endotoxemia (the presence of bacterial endotoxins in the blood), activation of the TOx pathway, and the chronic inflammatory state of progressive HIV disease (1). Researchers currently are developing targeted therapies to alter TOx activation in a number of disease contexts, and a richer understanding of pathway regulatory mechanisms will help to guide these drug discovery and development efforts. Here various aspects of TOx regulation are examined from the perspective of potential therapeutic intervention.




TOX PATHWAY PERMUTATIONS




As an essential amino acid, Trp cannot be synthesized in humans and must be obtained through the diet. Dietary Trp feeds into three major metabolic pathways: (i) protein synthesis; (ii) synthesis of the neurotransmitter serotonin; and (iii) TOx, to form either energy [adenosine triphosphate (ATP)], nicotinamide and related compounds [nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)], or other side products (such as xanthurenic acid). In humans, oxidative catabolism of Trp can be initiated by one of three different enzymes: tryptophan-2,3-dioxygenase (TDO2) in the liver, as well as IDO1 and IDO2, which have incompletely overlapping nonhepatic tissue distributions. These three enzymes open the indole ring, causing the irreversible loss of Trp (2). The TOx pathway is interconnected with other metabolic networks (3) and is variously regulated in a number of tissues.




The liver is thought to be the only organ with substantial TDO2 activity, and this enzyme is not believed to drive the immunoregulatory effects of TOx. Instead, TDO2 is induced by dietary protein and corticosteroids, but not by cytokines such as interferon-γ (IFN-γ) (4). Recent work by Schmidt et al. demonstrated an in vitro immunoregulatory effect associated with TDO2 activity, which may implicate the activity of pathway metabolites more than a clinically significant in vivo effect, although a contribution to immunomodulation within the liver has not been excluded (5). The hepatic end products generated via activation of this pathway are ATP, CO2, and water.




The metabolic pathway initiated by the extrahepatic enzymes IDO1 and IDO2 is shown in Fig. 1. IDO1 and IDO2 are inducible and less substrate-specific for Trp than TDO2. While there are many cytokine inducers of IDO-mediated TOx, the most effective pathway inducer appears to be IFN-γ (4). That said, there are important tissue-specific differences in cytokine induction, leading to different tissue responses to the same systemic signals. For example, in the brain it appears that interleukin-6, and not IFN-γ, drives IDO induction (6). Elucidation of the differences in IDO1- versus IDO2-induced cytokine responses will require further study. Many different microbial infections?bacterial, viral, and parasitic?have been implicated in IDO-induced TOx (7), and a number of microbial products can directly induce the pathway. Bacterial LPS and the HIV-Nef and HIV-Tat proteins are among the best-studied but are not likely to be unique in this capability.



The second enzyme in the TOx pathway is arylformamidase (AFMID), which is responsible for converting the dioxygenase product (N-formyl-kynurenine) to l-kynurenine (l-KYN). l-KYN is subsequently converted to 3-hydroxy-l-kynurenine (3-HKA) by kynurenine 3-monooxygenase (KMO), and 3-HKA is metabolized to 3-hydroxy-anthranilic acid (3-HAA) by kynureninase (KYNU). Favre et al. noted that the 3-HKA and 3-HAA metabolites have effects on the T helper 17 cell (TH17)?to?regulatory T cell (Treg) ratio in vitro (1). It appears that 3-HAA is removed from the tissue microenvironment only by the action of another dioxygenase, 3-hydroxyanthranilate 3,4-dioxygenase (HAAO). This means that, in order to prevent the in vivo accumulation of 3-HAA and its potential effects on T cell ratios, the organism is dependent on the relative activity of this specific enzyme. Outside of the central nervous system (CNS), TOx pathway activation does not lead to the accumulation of quinolinic acid (QA), suggesting that the relative activities of the aminocarboxymuconate semialdehyde decarboxylase (ACMSD) and quinolinate phosphoribosyltransferase (QPRT) enzymes are sufficient to divert QA to other products. In a multistep process initiated by QPRT, the downstream metabolism of QA results in the formation of NAD, NADP, and nicotinamide. In general, it is presumed that the QPRT-driven pathway to nicotinamide and nicotinamide nucleotides occurs preferentially in the extrahepatic TOx pathway, and the ACMSD-driven subpathway to ATP appears to occur preferentially by hepatic TOx, although further detailed studies may alter this understanding (4). In the CNS, QA is produced locally in response to either local or systemic inflammatory signals and stimulates the N-methyl-d-aspartate (NMDA) receptor, a key component in learning and memory (8). Overstimulation of NMDA receptors can cause neurotoxic effects that have been implicated in neurological diseases.




In HIV-infected patients, the amounts of QA measured in the brain and cerebrospinal fluid (CSF) are greatly increased compared to those in controls. In one study (8), a 100-fold variation in the amounts of QA in the CSF and brain tissue was detected among HIV patients, and these elevations did not correlate with serum QA concentrations (8). These data suggest that the degradation of Trp via the TOx pathway is stalled in the CNS. This tissue-specific accumulation of QA may result from a relatively low amount of QPRT activity compared to that of HAAO and other upstream enzymes (Fig. 1). Recent work by Connor and colleagues revealed that systemic stimuli such as LPS induce IDO and KMO activities in the mammalian brain but do not alter kynurenine aminotransferase (KAT) activity (6). A critical question is whether QPRT is also inducible and under what circumstances, because this effect would have the potential to draw down the local QA concentrations and interrupt the neurotoxic effects associated with high concentrations of this metabolite.




OVERACTIVE TOX




The new work by Favre et al. builds on the relationship between LPS and TOx first reported in 1978 by Yoshida and Hayaishi (9) and the findings of Brenchley and others (in 2006) that HIV infection is marked by chronically elevated circulating amounts of LPS (10). Favre et al. place the observations of Terness and others regarding TOx metabolites into a new disease-specific context (11, 12) and provide evidence that the intermediate TOx metabolites 3-HKA and 3-HAA are regulators of a specific T lymphocyte subset ratio; namely, the TH17:Treg ratio (1). The loss of a normal TH17:Treg ratio in the gut is associated with increased LPS endotoxemia and persistent induction of TOx overstimulation in the setting of HIV (13). These data add to an impression that chronic TOx induction during HIV infection is a central pathogenic process that results in the disruption of normal T lymphocyte function and is driven by a combination of endogenous cytokines (particularly IFN-γ), viral products (the HIV-Tat and HIV-Nef proteins), and bacterial products (including LPS) (Fig. 2).



The detrimental effects of TOx induction in progressive HIV disease contrast with the demonstrable benefit of TOx activation in the normal placenta and the presumed value of TOx in limiting microbial access to Trp in some nonviral infections (14). In HIV infection, the mediators of TOx pathogenicity appear to be the altered concentrations of the pathway products, in particular Trp, 3-HKA, 3-HAA, and QA.




The growing interest in targeted therapies to alter TOx activation in cancer management (15) needs to be extended to HIV infection, as well as reproduction, organ transplantation, neurodegenerative diseases, and autoimmune syndromes, in which TOx pathway activation has also been implicated in aspects of disease pathogenesis (16?20).




TOX THERAPEUTIC TACTICS




There is accumulating evidence that small molecules that participate in the TOx pathway are capable of acting as immune regulators outside of their direct role in amino acid catabolism. Further study of the tissue-specific bioavailability of 3-HKA and 3-HAA is needed to confirm their in vivo significance in pathogenic immunoregulatory signaling; however, what emerges through the work to date is a model for chronic activation of IDO-associated TOx, leading to T lymphocyte dysregulation in HIV infection (Fig. 2). Given the number of diseases in which TOx activation appears to be linked to pathogenesis, it is likely that multiple clinical trials will emerge to test agents that might therapeutically manipulate this pathway. Oral Trp loading is one approach to avoid in going forward, except perhaps in a carefully controlled research setting, because it has been associated with both an increase in circulating TOx pathway intermediates (21) and the still poorly understood phenomenon of eosinophilia-myalgia syndrome (22).




As with any metabolic pathway, the pharmacological regulation of extrahepatic TOx can be approached in several ways. The approach that is currently being tried is inhibition of the first and rate-limiting step in the TOx pathway, namely IDO activity (both IDO1 and IDO2). This is being pursued with the competitive inhibitor 1-methyl-D-tryptophan (D-1MT), and there are currently at least four D-1MT trials (phase 1 and 2) in the clinical oncology domain (23). D-1MT was also used in a study of SIV?infected macaques, an animal model of HIV, with some benefit (24). A number of other IDO inhibitory molecules have been studied, but they have not yet progressed to clinical trials (25). There also is interest in the use of Trp catabolite mimetics, such as 3,4-DAA [N-(3,4-dimethyoxycinnamoyl) anthranilic acid], which is orally active and may represent a lead compound for inhibiting autoreactive TH1 cells in autoimmune diseases (20). Furthermore, it may be desirable in some therapeutic settings to differentially regulate IDO1 and IDO2 (26). Because a functional IDO2 gene product is not expressed in as many as 25 to 30% of certain human populations (27), the consequences of this natural experiment need to be better understood, so that they may guide our evolving understanding of how to successfully use pharmacological agents to inhibit this pathway.




Other conceptual therapeutic approaches that target TOx include (i) diverting the pathway from toxic intermediates or end products by inducing benign metabolic side-product formation, (ii) inducing downstream pathway activity to drive end-product formation and avoid the accumulation of toxic intermediates, and (iii) feedback inhibition of the pathway via increased end-product concentrations. On the basis of data that suggested that HIV-infected patients display a metabolic drive toward increased available nicotinamide (28), we initiated a very small clinical trial of oral nicotinamide in part to provide potential feedback inhibition of the TOx pathway (29). We found that oral nico‐tinamide administration resulted in increased circulating Trp in HIV-infected patients, but followup is needed to determine the clinical implications of this result (4, 29). Nicotinamide and other endogenous TOx-related compounds may ultimately prove to be useful adjuncts to therapy or lead compounds for the development of new pharmacological agents to treat HIV and other diseases associated with TOx-induced pathogenesis.


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Offline red_Dragon888

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Re: http://natap.org/
« Reply #135 on: May 24, 2010, 01:38:35 PM »
Prolonged Control of Viremia After Transfer of Autologous CD4 T ...
17th CROI Conference on Retroviruses and Opportunistic Infections ... Expressing Long Antisense to HIV env (VRX496). Reported by Jules Levin CROI 2010 ...
www.natap.org/2010/CROI/croi_182.htm


VIRxSYS Presents Results from Multiple Studies at the 13th ASGCT Annual Meeting
 
GAITHERSBURG, MD ? May XX, 2010 ?VIRxSYS Corporation, a privately held company developing vaccines and RNA therapies for serious diseases such as AIDS and cardiovascular disease, will present eight abstracts at the 13th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) taking place in Washington, DC, from May 17-22, 2010. The abstracts represent results of the company?s clinical trials for Lexgenleucel-T (VRX496?), an autologous cell and gene therapy product for the treatment of HIV/AIDS; preclinical trials of the company?s prophylactic HIV vaccine, VRX1273; and work utilizing the company?s spliceosome mediated RNA trans-splicing (SMaRT?) platform technology.
 
?We are honored to present so much of our research at the 13th ASGCT Annual Meeting,? said Dr. Riku Rautsola, PhD, President and CEO of VIRxSYS. ?Our clinical trials continue to demonstrate promising results as we work toward new treatments for HIV.  We are also pleased to see our SMaRTTM platform technology performing well in critical pre-clinical studies.?
 
Highlights of the presentations include data from VIRxSYS?s Phase 2 study of Lexgenleucel-T, which continue to show no evidence of long-term safety issues after the cumulative infusion of over 4 x 1012 vector copies in a total of 2 x 1012 modified CD4 T cells. To date, data from the Lexgenleucel-T clinical trial program comprises of the largest safety database of subjects enrolled in a clinical trial using a lentiviral vector. In accordance with FDA guidelines, all subjects will continue to be monitored for safety for up to 15 years. Additional data from the Lexgenleucel-T Phase 2 study demonstrate that the therapeutic efficacy of Lexgenleucel-T treatment is not affected by the development of anti-vector antibodies, nor is the development of these antibodies associated with clinically detectable adverse events, a common concern in gene therapy trials.
 
Other highlights include:
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #136 on: May 24, 2010, 01:39:29 PM »

 

Do n-3 fatty acids prevent osteoporosis?
Ovariectomized mice fed a diet high in fish oil had significantly less bone loss at the femur and lumbar vertebrae than did ovariectomized mice fed a diet ...
www.natap.org/2007/HIV/032607_02.htm
Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Diseases
J Am Coll Cardiol, 2009
Wang C, Harris WS, Chung M, et al. n-3 fatty acid from fish or fish-oil supplements .... Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular ...
www.natap.org/2009/HIV/080509_04.htm

Convincing evidence from extensive research over the past 3 decades points out the potential beneficial effects of -3 PUFA in primary prevention, CHD and post-MI, SCD, HF, atherosclerosis, and AF. Based on the growing evidence for the benefits of fish oils, we agree that this story represents a "fish tale withgrowing credibility."


A detailed discussion of all of the potential mechanisms of -3 PUFA and CV diseases (summarized in Table 2) is beyond the scope of this review. It appears that -3 PUFA confer CV benefits largely through DHA and EPA enrichment of membrane phospholipids (65). In addition to mechanisms discussed above, -3 PUFA produces vasodilation, reduces blood pressure (31,66), improves arterial and endothelial function (67), and reduces platelet aggregation (68). The antiplatelet, anti-inflammatory, and triglyceride-lowering effects of -3 PUFA (Fig. 5) (69) require relatively higher doses of DHA and EPA (e.g., 3 to 4 g/day), whereas some of the antiarrhythmic effects, reduction of SCD, and improvement in HF can be achieved at lower doses (500 to 1,000 mg/day). Nevertheless, higher doses may be even more effective in HF, as discussed previously. Although the effects of -3 PUFA on C-reactive protein levels have been inconsistent (70), these agents have been shown to suppress production of pro-inflammatory cytokines such as interleukin-1B, interleukin-6, and tumor necrosis factor-alpha (71). When administered to obese patients, 1.8 g of EPA increased the levels of adiponectin, which can reduce inflammation and improve insulin sensitivity (72), in addition to the potential beneficial HF effects discussed earlier. Although benefits on the autonomic nervous system are well established and are reviewed earlier, studies in patients undergoing heart transplantation suggest that -3 PUFA can reduce heart rate independently of vagal activation (73), in addition to reducing mean arterial pressure and systemic vascular resistance by 25% and reducing LV hypertrophy and improving diastolic function in heart transplantation patients with cyclosporine-induced hypertension (66).


Fish Reduces Risk of Dementia by 47% in Framingham Heart Study
Nov 11, 2006 ... from the diet or can be obtained directly by consuming foods rich in DHA such as fish or fish oil or supplements containing DHA. ...
www.natap.org/2006/HIV/121806_06.htm


Heart Association Recommends Daily Intake of Omega-6 Fatty Acids
Jan 26, 2009 ... omega-3 fatty acid a-linolenic acid,57,59,60 and simultaneous recommendations to increase fish and cod liver oil use.58 Nevertheless, ...
www.natap.org/2009/HIV/012809_02.htm


Nut-Enriched Mediterranean Diet Helps Reverse Metabolic Syndrome
"The traditional MedDiet is characterized by a high intake of cereals, vegetables, fruits, and olive oil; a moderate intake of fish and alcohol, ...
www.natap.org/2008/HIV/120908_01.htm


Fish Intake, Contaminants, and Human Health
Oct 18, 2006 ... Fish oil capsules contain 20% to 80% of EPA and DHA by weight (200-800 mg/g185-
186), little to no mercury,187 and variable levels of PCBs ...
www.natap.org/2006/HIV/102606_11.htm


http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #137 on: May 25, 2010, 06:24:41 AM »
NATAP http://natap.org/
_______________________________________________




Upcoming FDA Advisory Committee Meeting on Egrifta (tesamorelin acetate) to reduce excess visceral abdominal fat in HIV-related lipodystrophy


Food and Drug Administration - March 22, 2010
Richard Klein & Kimberly Struble

--------------------------------------------------------------------------------
The Food and Drug Administration (FDA) will hold a public meeting of its Endocrinologic and Metabolic Drugs Advisory Committee to discuss the safety and efficacy of new drug application (NDA) 22-505, EGRIFTA (tesamorelin acetate), sterile lyophilized powder for injection, by Theratechnologies, Inc. EGRIFTA is an analogue (a chemical compound that resembles another compound in structure) of growth hormone releasing hormone (GHRH). The proposed indication (use) for EGRIFTA in this application is to induce and maintain a reduction of excess visceral abdominal fat in human immunodeficiency virus (HIV)-infected patients with lipodystrophy (a condition in which abnormal deposits of fat are seen partly as a result of using certain drugs to treat HIV disease).


The meeting will take place on May 27, 2010, from 8 a.m. to 5 p.m, at The Inn and Conference Center, University of Maryland University College (UMUC), 3501 University Blvd. East, Adelphi, MD. You can contact the hotel directly at 301-985- 7300 for directions or to arrange accomodations.
The meeting will be open to the public, and no registration is required.


Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.


Written submissions may be made to Paul Tran, Center for Drug Evaluation and Research (HFD- 21), Food and Drug Administration, 5600 Fishers Lane (for express delivery, 5630 Fishers Lane, rm. 1093) Rockville, MD 20857, 301-827-7001, FAX: 301- 827-6776, e-mail: paul.tran@fda.hhs.gov on or before May 13, 2010.


Oral presentations from the public (the open public hearing) will be scheduled between approximately 1 p.m. and 2 p.m. Those desiring to make formal oral presentations should notify Paul Tran, and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before May 5, 2010.


Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session.
Those requesting time to present will be notified regarding their request to speak by May 6, 2010.


FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its Web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA's Web site after the meeting. Background material can be found at http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm. Scroll down to the appropriate advisory committee link.


Please call the FDA Advisory Committee Information Line for up-to-date information about this meeting, at 1-800-741-8138 (301-443-0572 in the Washington, DC area), and use code 3014512536. A notice in the Federal Register about last minute modifications that impact a previously announced advisory committee meeting cannot always be published quickly enough to provide timely notice. Therefore, you should always check the agency's Web site and call the appropriate advisory committee hot line/phone line to learn about possible modifications before coming to the meeting.


Persons attending FDA's advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.


FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Paul Tran at least 7 days in advance of the meeting.
FDA is committed to the orderly conduct of its advisory committee meetings. Please visit our Web site at http://www.fda.gov/ AdvisoryCommittees/AboutAdvisoryCommittees/ucm111462.htm for procedures on public conduct during advisory committee meetings.


Richard Klein
Office of Special Health Issues
Food and Drug Administration


Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
100322
FD100302
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #138 on: May 26, 2010, 04:32:56 PM »
FDA:Theratechnologies Drug Cuts Abdominal Fat In HIV Patient


By Jennifer Corbett Dooren
Of DOW JONES NEWSWIRES
 WASHINGTON (Dow Jones)--A proposed Theratechnologies Inc. (THTCF) drug cut abdominal fat in HIV patients, but might increase the risk of
diabetes, a U.S. Food and Drug Administration staff review said Tuesday.


Theratechnologies, based in Montreal, is seeking FDA approval for a proposed drug tesamorelin to treat HIV-associated lipodystrophy, an accumulation of a specific type of fat in the abdominal region that puts patients at risk of developing cardiovascular disease.


Tesamorelin, which the company has proposed selling under the brand name Egrifta, faces a review on Thursday by the FDA's Endocrinologic and Metabolic Drugs Advisory Committee.


The committee, which is made up of non-FDA medical experts, is being asked to vote on whether it thinks the product should be approved. The product, an insulin-like shot that would be self-injected daily, is designed to help the body produce a growth hormone.


In briefing documents posted to the FDA's website Tuesday, agency staff reviewers said patients treated with tesamorelin had their levels of excess abdominal fat reduced by an average of 17.5%. However, the FDA said the fat mostly returned after treatment was stopped, suggesting patients would have to be treated with tesamorelin on an on-going basis.


Two studies were conducted that involved a total of 816 patients. During the studies 543 patients received tesamoralin while the rest received a placebo, or fake treatment for six months. At the end of the study, patients in the placebo group were then treated with tesamorelin for six months while patients previously treated with the drug were re-randomized to stay on the drug or receive a placebo shot. FDA's review said more patients developed diabetes during the study compared to patients receiving a placebo, while some patients in the study shifted from what's considered pre-diabetes to diabetes during treatment.


In Toronto Tuesday, shares of Theratechnologies have dropped 54% to C$2.02.


Canaccord Genuity analyst Neil Maruoka said the diabetes risk came as a surprise, but said questions about whether the product could reduce the risk of cardiovascular disease were expected.


Lipodystrophy was thought to be solely associated with anti-retroviral drugs that are used to treat HIV but there's evidence that having HIV itself plays a role.


Daniel Berger, an HIV specialist and founder of Northstar Healthcare in Chicago, said about 25% of HIV patients have lipodystrophy, which is marked by an accumulation of visceral fat or fat inside the body cavity. It differs from subcutaneous fat, or that type of fat that accumulates underneath the skin, and is thought to be more dangerous. Berger was one of the leaders of tesamorelin's clinical studies.


Theratechnogolies noted, in a document also posted to FDA's website, that there's no approved treatment for lipodystrophy and said tesamorelin has a "positive impact" on reducing visceral fat. The company also said some patients stop their anti-retroviral therapy which puts them at risk of HIV progression and other complications.


-By Jennifer Corbett Dooren, Dow Jones Newswires; 202-862-9294; jennifer.corbett@dowjones.com
-Andy Georgiades contributed to this report.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #139 on: May 29, 2010, 10:43:47 AM »
_______________________________________________

Clean Teeth Again Linked to Healthy Heart
"Low-grade inflammation appeared to be playing a role.....the risk of a fatal or nonfatal event was 40% greater for those who brushed once rather than twice a day and 2.3-fold higher for those who brushed less than once a day....They also had increased concentrations of both C reactive protein [inflammation marker] (β 0.04, 0.01 to 0.08) and fibrinogen (0.08, ?0.01 to 0.18).....The literature clearly shows that raised pro-inflammatory cytokines are present in both cardiovascular disease and periodontal disease"

MedPage Today
Published: May 28, 2010

Regular toothbrushing could help stave off cardiovascular disease, according to a nationally-representative study in Scotland.

Action Points 
--------------------------------------------------------------------------------
Explain to interested patients that poor dental hygiene -- brushing less than twice daily -- is thought to be a major cause of periodontal disease and may also impair cardiovascular health.


Individuals who rarely or never brushed were 70% more likely to have a heart attack or other cardiovascular disease event (P<0.001) even after controlling for many other factors, found researchers led by Richard Watt, MSc, PhD, of University College London.


Even brushing once a day rather than twice a day was associated with a significant 30% increase in the risk of these fatal or nonfatal events.


Low-grade inflammation appeared to be playing a role, although whether it is a causal role remains uncertain, Watt's group reported online in BMJ.


These increases in risk could have a "profound public health impact," they wrote in the study.
Nearly 40% of the population has some degree of periodontal disease, a complex chronic inflammatory condition largely caused by poor oral hygiene, the investigators noted.


Its link to cardiovascular disease has been extensively studied with results affirmed and strengthened by the new population-level data.


The researchers used self-reported frequency of toothbrushing as a proxy for periodontal disease, which wouldn't have been feasible for a large-scale population study, they said.


The analysis included 11,869 men and women ages 35 and older (mean 50) who retained their natural teeth and were without preexisting cardiovascular disease in the 1995, 1998, and 2003 iterations of the Scottish Health Survey of the general population.


Overall, their oral health was good. Regular visits to a dentist at least every six months were reported by 62% of respondents and 71% reported brushing twice a day.


More frequent toothbrushing appeared to be dose-dependently protective against cardiovascular disease events -- fatal or nonfatal, including cardiovascular disease-related hospitalization, acute MI, coronary artery bypass surgery, percutaneous coronary angioplasty, stroke, and heart failure.
In the analysis adjusted only for age and sex, the risk of a fatal or nonfatal event was 40% greater for those who brushed once rather than twice a day and 2.3-fold higher for those who brushed less than once a day (P=0.001 for trend).


Further adjustment for socioeconomic status, smoking, physical activity, and visits to the dentist attenuated the link. Additional controls for body mass index, family history of cardiovascular disease, hypertension, and physician-diagnosed diabetes also reduced the relationship but not to the point where significance was lost.


For cardiovascular disease-related death alone, similar trends were seen with a 10% elevated risk with once-a-day brushing and 50% elevated risk with less than once-a-day brushing compared with twice daily. However, this relationship lost significance with multivariate adjustment.


The other independent predictors of fatal and nonfatal cardiovascular disease events combined included:
Smoking (hazard ratio 2.4, 95% confidence interval 1.9 to 2.9)
Hypertension (HR 1.7, 95% CI 1.4 to 2.0)
Diabetes (HR 1.9, 95% CI 1.4 to 2.7)
A subgroup of 4,830 study participants gave blood samples from which markers of inflammation (C reactive protein) and coagulation (fibrinogen) were measured.


Among them, less frequent toothbrushing appeared to have an effect that remained significant after multiple adjustments (P=0.46 for trend in C reactive protein levels and P=0.015 for trend in fibrinogen levels).


Inclusion of inflammatory markers partly attenuated the point estimates for the link between toothbrushing and cardiovascular disease "thus suggesting a possible mediating role," Watt's group wrote in BMJ.


They cautioned that residual confounding may have played a role as well.


Even though the study could not prove that inflammation from poor dental hygiene was causing the increase in cardiovascular events, Watt and colleagues concluded that "educating patients in improving personal oral hygiene is beneficial to their oral health regardless of the relation with systemic disease."




BMJ, 27 May 2010


"Toothbrushing, inflammation, and risk of cardiovascular disease: results from Scottish Health Survey"


Discussion
Abstract
Introduction
Methods
Results
Discussion
References


Toothbrushing is associated with cardiovascular disease, even after adjustment for age, sex, socioeconomic group, smoking, visits to dentist, BMI, family history of cardiovascular disease, hypertension, and diagnosis of diabetes. Our results largely confirm those of previous studies.20 21 We examined the association between toothbrushing behaviour and cardiovascular disease and whether markers of low grade inflammation/coagulation were associated with low frequency of toothbrushing. Our results also suggest that toothbrushing is associated with concentrations of C reactive protein and fibrinogen. To the best of our knowledge, this is the first study to show an association between a single item self reported measure of toothbrushing and incident cardiovascular disease in a large representative sample of adults without overt cardiovascular disease. As self reported measures of oral hygiene have been associated with clinically confirmed periodontal disease,13 a simple self report measure of toothbrushing could therefore be associated with future risk for cardiovascular disease.


Oral health and cardiovascular disease
The role of oral health in the aetiology of cardiovascular disease has received considerable attention. Periodontal disease is a complex chronic inflammatory disease, resulting in a loss of connective tissue and bone support of the teeth.22 It is a major cause of tooth loss in adults aged over 40, and, according to the World Health Organization, affects people worldwide at prevalence rates of up to 10-20% for the most severe forms.23 Periodontal disease is highly prevalent, especially in late middle age when coronary artery disease is also most common,24 and it is caused mostly by poor oral hygiene.


In our study, participants who brushed their teeth less often had a 70% increased risk of a cardiovascular disease event in fully adjusted models. These results confirm findings from several observational epidemiological studies that showed that poor periodontal health status is associated with an increased risk of cardiovascular disease.1 In a study of 15 year follow-up data from the First National Health and Nutritional Examination Survey (NHANES I) Epidemiologic Follow-up Study, DeStefano et al found that people with periodontal disease had a 25% increased risk for coronary heart disease relative to those with minimal periodontal disease, after adjustment for age, sex, race, education, poverty index, marital status, systolic blood pressure, total cholesterol concentration, diabetes, BMI, and alcohol consumption.25 In a longitudinal study, Beck et al found that the odds ratios were 1.5 for total coronary heart disease and 1.9 for fatal coronary heart disease among people with periodontal bone loss compared with those without bone loss, after adjustment for several risk factors for cardiovascular disease.26


One meta-analysis concluded that periodontal disease and poor oral health overall indeed contribute to the pathogenesis of cardiovascular disease.27 Another meta-analysis, by Bahekar et al, confirmed that having periodontal disease might enhance the risk for cardiovascular disease but concluded that this risk was not robust.20


Periodontal disease seems to be associated with a 19% increase in the risk of future cardiovascular disease. This increase in relative risk is more prominent (44%) in people aged under 65. The increment of risk between people with or without periodontal disease in the general population is modest, at around 20%, because nearly 40% of the population have periodontal disease. This modest increase might, however, have a profound public health impact.28
In our study, less frequent toothbrushing was associated with increased concentrations of both C reactive protein and fibrinogen, and these associations remained significant after multiple adjustments including acute infections such as influenza. The work on serum markers of inflammation in both cardiovascular and periodontal research is extensive. The literature clearly shows that raised pro-inflammatory cytokines are present in both cardiovascular disease and periodontal disease. As a result, accumulating evidence has associated severe periodontal disease with increased odds of future cardiovascular disease events.3 Our study suggests a possible role of poor oral hygiene in the risk of cardiovascular disease via systemic inflammation. Raised inflammatory and homoeostatic responses as well as lipid metabolism disturbance caused by periodontal infection might be possible pathways underlying the observed association between periodontal disease and the increased risk for cardiovascular disease.29 Few studies, however, have examined these potential pathways. If these biological mechanisms are responsible for a slight increase in the risk of cardiovascular disease, better controlled and larger studies will be needed to identify them. Such efforts would be important because of the relatively high prevalence of periodontal disease.


Strengths and limitations
The Scottish Health Survey is nationally representative, with a rigorous design and data linked to a patient based database of hospital admissions and deaths with follow-up. The Scottish population is relatively homogeneous, with a high incidence of cardiovascular disease and poor indicators of oral health, thus our findings have high relevance to this population.


Though clinical data regarding the periodontal disease status of the participants might have strengthened our findings, previous research has also shown a good correlation between self report and clinical evaluation of periodontal disease.13 We had no follow-up data on toothbrushing behaviour. There is, however, evidence showing stability of oral health related behaviour such as toothbrushing and dental flossing,30 thus small changes in oral health behaviour are unlikely to affect the present findings. Both residual confounding and potential influence of effect modifiers could be responsible for a substantial attenuation of the relative risk in fully adjusted models. In addition, misclassification of both the exposure and the outcome could have played a role.


Conclusions
Our results confirmed and further strengthened the suggested association between oral hygiene and the risk of cardiovascular disease. Furthermore, inflammatory markers were significantly associated with poor oral health behaviour. Future experimental studies will be needed to confirm whether the observed association between oral health behaviour and cardiovascular disease is in fact causal or merely a risk marker. Nevertheless, use of a simple one item measure of self reported toothbrushing could be a useful and cost effective marker of future health risk in large scale population studies.


Given the high prevalence of oral infections in the population, doctors should be alert to the possible oral source of an increased inflammatory burden. In addition, educating patients in improving personal oral hygiene is beneficial to their oral health regardless of the relation with systemic disease.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #140 on: May 29, 2010, 10:45:43 AM »
http://oudaily.com/news/2010/may/28/ou-researchers-discover-vaccine-potential-treat-hi/

OU researchers discover vaccine with potential to treat HIV, cancer
Daily Staff Report/The Daily
Friday, May 28, 2010


 
Microbiology professor William Hildebrand. Photo provided.
 
For the first time, OU researchers have discovered a way to create a new vaccine using a protein that activates a distinct part of the immune system.

The OU Health Sciences Center research has potential treatment and prevention applications for cancer, tuberculosis, HIV and several other viral diseases, according to a press release from the HSC.

Until now, vaccines have focused on generating antibodies, or B-cells, to keep from getting sick. But this T-cell vaccine uses a protein to activate a distinct part of the immune system, according to the release.

?No one has ever done this with a T-cell vaccine, so we?re learning; but now we are starting to get some traction. We are finding that a T-cell vaccine can work,? said William Hildebrand, the lead researcher on the project.

Hildebrand and his research team have been working with the body's alarm system to learn how cells alert the immune system that something is wrong. The goal is to create viable targets for vaccines that activate T-cells in the immune system, said Hildebrand, microbiology and immunology professor.

T-cells are responsible for killing virus-infected cells in the body. T-cells also kill cells that become cancerous. Some vaccines such as the smallpox vaccine activate T-cells, but this occurs inadvertently. Until now, vaccines have focused on generating antibodies to keep people from getting sick, according to the release.

While many of these antibody vaccines work well, the dependence on antibodies has prompted some viruses to skirt antibody immunity, making vaccines less effective or not effective at all for some viruses. With a T-cell vaccine, researchers would be able to activate another arm of the immune system to target a specific virus in the body and kill it.

To develop the vaccine, Hildebrand began by determining how the immune system distinguishes between a virus-infected or cancerous cell and a healthy cell.

Researchers started with West Nile virus since it doesn't change like the flu or develop resistance like cancer or HIV. After developing the target, researchers at the HSC worked with colleagues at Washington University in St. Louis to create a vaccine, the release stated.

The process is now being repeated for targets and vaccines in other areas, such as cancer, where activating T-cells can be difficult.

"Now that we have demonstrated the feasibility of developing a T-cell-specific vaccine, we intend to use the same process to discover other reliable targets, validate them and develop additional vaccines,? Hildebrand said.

The research appears in the latest issue of The Journal of Immunology and is funded by grants and contracts totaling $15 million from the National Institutes of Health, according to the release.
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Re: http://natap.org/
« Reply #141 on: June 01, 2010, 10:52:25 AM »
Vaginal Gel That Kills Herpes, HIV May Be Available by 2012 (Just in time for the end of the World)

May 31, 2010


June 1 (Bloomberg) -- The world?s first herpes-killing vaginal gel may be available within two years, said its developer Starpharma Holdings Ltd., which plans to start patient studies on its effectiveness.


Starpharma is in discussions with ?a number of groups? about trials of its VivaGel product in women at risk of contracting genital herpes, Chief Executive Officer Jackie Fairley said in an interview in Singapore, declining to identify the partners. The Melbourne-based company licensed its VivaGel- coated condoms in 2008 to SSL International Plc, maker of the world?s best-selling Durex brand.


No cure exists for genital herpes, a condition that infects about one in six Americans and produces painful sores and increases HIV transmission, U.S. Centers for Disease Control and Prevention data show. While other gels are being developed to prevent HIV infections, VivaGel is the only microbicide designed to stop herpes infections, Fairley said.


?Commercially it?s actually the herpes market which we think is a more important market? than that for HIV, she said May 27. ?Because herpes is such a massive problem, particularly in the U.S., we think that the herpes opportunity alone is more than attractive enough.?


The company expects to complete the discussions on funding this year, before setting a date for trials to start, Fairley said. Starpharma is also seeking public funding for separate studies of VivaGel aimed at preventing HIV infection, she said.


Deadliest Disease


Trials of microbicides have so far failed to prevent the spread of HIV, the world?s deadliest infectious disease, which kills about 2 million people each year, according to World Health Organization figures.


PRO 2000, a gel made by Endo Pharmaceuticals Holdings Inc. failed in a late-stage trial in December after an earlier study suggested it worked.


Carraguard, a gel produced from seaweed that was developed by New York-based nonprofit group Population Council, flopped in 2008. A year earlier, tests of a product called Ushercell, from Toronto-based Polydex Pharmaceuticals Ltd., were halted after more of the women who used it became infected with HIV than those who received a placebo.


A trial of VivaGel in 61 healthy, sexually active women showed the product was safe, Starpharma said in March. The company plans to study the product?s effectiveness against bacterial vaginosis, the most common vaginal infection in women of childbearing age, later this year, it said at the time.


Condoms are more effective at preventing HIV than genital herpes because the herpes virus is spread through sores on the skin.


Starpharma, which said in September 2008 that VivaGel is designed to halt both viruses, expects to start receiving royalties from condom maker SSL, in 2011, Fairley said.


Starpharma shares have slumped 28 percent since reaching a five-year high of 75 Australian cents in February. The company had A$23.7 million in cash as of Dec. 31 and doesn?t plan to use that money to fund its trials, Fairley said.


--Editors: Lena Lee, Carey Sargent.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #142 on: June 01, 2010, 11:18:36 AM »
Hopes for breast cancer vaccine - pdf attached full article
 
A radiologist studies mammograms 
news.bbc



American scientists say they have developed a vaccine which has prevented breast cancer from developing in mice.


The researchers - whose findings are published in the journal, Nature Medicine - are now planning to conduct trials of the drug in humans.


But they warn that it could be some years before the vaccine is widely available.


The immunologist who led the research says the vaccine targets a protein found in most breast tumours.


Vincent Tuohy, from the Cleveland Clinic Learner Research Institute, said: "We believe that this vaccine will someday be used to prevent breast cancer in adult women in the same way that vaccines have prevented many childhood diseases.


Unique challenge
"If it works in humans the way it works in mice, this will be monumental. We could eliminate breast cancer."


In the study, genetically cancer-prone mice were vaccinated - half with a vaccine containing ?-lactalbumin and half with a vaccine that did not contain the antigen.


None of the mice vaccinated with ?-lactalbumin developed breast cancer, while all of the other mice did.


The US has approved two cancer-prevention vaccines, one against cervical cancer and one against liver cancer.


However, these vaccines target viruses - the human papillomavirus (HPV) and the Hepatitis B virus (HBV) - not cancer formation itself.


 

 We look forward to seeing the results of large-scale clinical trials to find out if this vaccine would be safe



Caitlin Palframan, Breakthrough Breast Cancer

 
In terms of developing a preventive vaccine, cancer presents problems not posed by viruses - while viruses are recognised as foreign invaders by the immune system, cancer is not.


Cancer is an over-development of the body's own cells. Trying to vaccinate against this cell over-growth would effectively be vaccinating against the recipient's own body, destroying healthy tissue.


Caitlin Palframan, of charity Breakthrough Breast Cancer, said: "This research could have important implications for how we might prevent breast cancer in the future.


"However, this is an early stage study, and we look forward to seeing the results of large-scale clinical trials to find out if this vaccine would be safe and effective in humans."


She added there were already steps women could take to reduce the risk of breast cancer, including reducing alcohol consumption, maintaining a healthy weight and taking regular exercise.
Cancer Research UK's professor of oncology, Robert Hawkins, said: "This very early study describes an interesting approach to the prevention of breast cancer.


"It will be several years before this vaccine can be tested fully to assess its safety and effectiveness as a way to stop the disease developing in women."


Breast cancer is the most common cancer in the UK, affecting more than 45,500 women every year.


The study authors gave vaccinations to mice that were genetically engineered to be susceptible to cancer. The mice that were vaccinated with an anti-cancer antigen didn't develop tumors, but all the others did.


Researchers say the vaccine would be targeted at women over the age of 40, because it disrupts breast-feeding and older women are less likely to become pregnant. Older women are also more likely to develop breast cancer.
----------------


Nature Medicine | Letter
Published online
30 May 2010
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #143 on: June 02, 2010, 07:34:45 AM »
NATAP http://natap.org/
_______________________________________________

Microbicides Conference
May 22-25, 2010
Pittsburgh, Pennsylvania

New ARTs Research Takes The Lead: HIV Microbicides Conference Report - (05/28/10)

Researchers upbeat on ART/HIV drugs as Microbocides: We hope that by 2012, we would have found evidence to the fact that ARVs do work in preventing HIV transmission

By Paidamoyo Chipunza recently in PENNSYLVANIA, US

HIV and Aids researchers from across the world are hopeful there will be breakthroughs in two years that will bring a glimmer of hope to people infected with the virus.

Speaking at the International Microbicide Conference that ended in Pittsburgh last week, Pro-Vice Chancellor of the University of KwaZulu Natal in South Africa Dr Salim Abdool Karim was optimistic that by 2012, technological developments would enable researchers to tell if participants of current research were adhering to trial drugs.

Prof Karim said: "Currently, there is no way we can tell that these participants are adhering to their drugs except to take participant?s word of mouth and this really affects the results.

"We hope technological developments will speed up the whole process of conducting clinical trials and gathering information from participants."

Leading Zimbabwean researcher Professor Mike Chirenje, who is working with the University of Zimbabwe in collaboration with the University of San Francisco in California, was confident that the next two years would prove or disprove the safety of microbicides use in pregnant women.

"We do not know if microbicide use is safe in pregnant women. Several studies are currently underway to determine if the use of these chemicals is safe for development of the foetus. Results of these studies are expected before 2012," Prof Chirenje said.

Chief executive officer of the International Partnership for Microbicides Dr Zeda Rosenberg said the future of HIV prevention lay in antiretroviral drugs.

"There is future in antiretroviral drugs. We hope that by 2012, we would have found evidence to the fact that ARVs do work in preventing HIV transmission," Dr Rosenberg said.

The microbicide conference is held biannually to evaluate progress in global HIV research.

This year?s meeting ? unlike previous conferences ? covered other HIV prevention strategies such as male circumcision and ARVs among other issues.

The conference?s theme was "Building bridges in HIV prevention".

The next high-level meeting has been scheduled for Australia in 2012.

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Re: http://natap.org/
« Reply #144 on: June 02, 2010, 07:36:13 AM »
Control Serum Glucose to Reduce HF Risk in Diabetics

MedPage Today
Published: June 01, 2010

BERLIN -- For patients with diabetes, moderate chronic kidney disease, and anemia, glycated hemoglobin (HbA1c) and estimated glomerular filtration rate (GFR) are independent risk factors for developing heart failure, researchers reported here.

Those findings emerged from a post hoc analysis of data from the Trial to Reduce Cardiovascular Events with Aranesp (TREAT) study, which revealed that the hazard ratio for developing heart failure was 1.11 for every 1% increase in HbA1c from baseline (P=0.002, 95% CI 1.04 to 1.19), said Eldrin F. Lewis, MD, of Harvard Medical School and Brigham and Women's Hospital in Boston.

For estimated GFR, heart failure risk decreased with every 1 unit increase from baseline (HR 0.99, 95% CI 0.98 to 1.00, P=0.047), Lewis reported in a late-breaking clinical poster presented here at the Heart Failure Congress.

Action Points 
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This analysis suggests that tight management of modifiable risk factors such a HbA1c and estimated GRF may reduce the risk for developing heart failure in anemic patients with diabetes or chronic renal disease.


Point out that these conclusions come from a post-hoc analysis and therefore can be considered hypothesis generating only.


Note that this study was published as a poster and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


In an interview with MedPage Today, Lewis said the strongest independent predictor of heart failure among patients in the TREAT study was a history of heart failure (HR, 2.47 95% CI 1.98 to 3.07, P<0.001), followed by baseline loop diuretic use (HR 1.64, 95% CI 1.28 to 2.09, P<0.001), and history of myocardial infarction (HR 1.48, 95% CI 1.19 to 1.85 P<0.001).


But, he said the analysis indicated it is "the modifiable risk factors such as diabetes and estimated GFR that should be the focus of prevention efforts."


The TREAT study enrolled 4,038 patients with diabetes, chronic kidney disease (defined as estimated GFR of 20 to 60 mL/min/1.732) and anemia, defined as hemoglobin ≤11 g/dL. The patients were randomized to darbepoetin (Aranesp) or placebo and followed for a median of 29 months.


The median age of the patients was 68 and 57% were women. The median estimated GFR was 34 mL/min/ 1.732. Roughly 18% of the study population had a history of myocardial infarction and 10.7% had a confirmed history of heart failure.


Overall, 10.7% of the TREAT patients developed heart failure during follow-up. In this group, age, a history of heart failure, higher HbA1c, lower estimated GFR, a history of myocardial infarction, male gender, and baseline use of loop diuretics were independently associated with increased risk of acute heart failure or cardiovascular death.


Included in the 434 patients who developed heart failure, there was a subset of 173 patients who developed incident heart failure during follow-up.


Lewis said that when he and his colleagues analyzed data from this subset, they discovered similar patterns of risk factors as independent predictors.


The TREAT trial investigated the potential role for darbepoetin alfa (Aranesp) for treatment of patients with diabetes or chronic renal disease and anemia. The trial found no benefit for darbepoetin alfa but did reveal a doubling of the risk for stroke. In this analysis, there was no significant association between randomization to darbepoetin alfa and incident heart failure.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #145 on: June 02, 2010, 07:38:22 AM »
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NATAP http://natap.org/
_______________________________________________

Microbicides Conference
May 22-25, 2010
Pittsburgh, Pennsylvania

New ARTs Research Takes The Lead: HIV Microbicides Conference Report - (05/28/10)

Researchers upbeat on ART/HIV drugs as Microbocides: We hope that by 2012, we would have found evidence to the fact that ARVs do work in preventing HIV transmission

By Paidamoyo Chipunza recently in PENNSYLVANIA, US

HIV and Aids researchers from across the world are hopeful there will be breakthroughs in two years that will bring a glimmer of hope to people infected with the virus.

Speaking at the International Microbicide Conference that ended in Pittsburgh last week, Pro-Vice Chancellor of the University of KwaZulu Natal in South Africa Dr Salim Abdool Karim was optimistic that by 2012, technological developments would enable researchers to tell if participants of current research were adhering to trial drugs.

Prof Karim said: "Currently, there is no way we can tell that these participants are adhering to their drugs except to take participant?s word of mouth and this really affects the results.

"We hope technological developments will speed up the whole process of conducting clinical trials and gathering information from participants."

Leading Zimbabwean researcher Professor Mike Chirenje, who is working with the University of Zimbabwe in collaboration with the University of San Francisco in California, was confident that the next two years would prove or disprove the safety of microbicides use in pregnant women.

"We do not know if microbicide use is safe in pregnant women. Several studies are currently underway to determine if the use of these chemicals is safe for development of the foetus. Results of these studies are expected before 2012," Prof Chirenje said.

Chief executive officer of the International Partnership for Microbicides Dr Zeda Rosenberg said the future of HIV prevention lay in antiretroviral drugs.

"There is future in antiretroviral drugs. We hope that by 2012, we would have found evidence to the fact that ARVs do work in preventing HIV transmission," Dr Rosenberg said.

The microbicide conference is held biannually to evaluate progress in global HIV research.

This year?s meeting ? unlike previous conferences ? covered other HIV prevention strategies such as male circumcision and ARVs among other issues.

The conference?s theme was "Building bridges in HIV prevention".

The next high-level meeting has been scheduled for Australia in 2012.
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Offline WhySoUnfair

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Re: http://natap.org/
« Reply #146 on: June 02, 2010, 12:00:18 PM »
1.5 more years, fingers & toes crossed...

Offline red_Dragon888

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Re: http://natap.org/
« Reply #147 on: June 02, 2010, 03:43:40 PM »
HIV-associated neurocognitive disorders: is there a hidden epidemic? - Editorial Comment



"the population of HIV-infected individuals is aging and further study is needed to assess the concatenation of age-related and HIV-related cognitive deterioration. We cannot ignore the very unique characteristics of the brain as a potential sanctuary for persistent infection and ongoing inflammatory damage.......the data suggest that we cannot be complacent and assume that systemic virological and immunological control will uniformly control CNS disease.....we must develop and promulgate screening techniques to detect and track HAND and screening should be included in routine care. Furthermore, integration of these data into treatment guidelines is important and the assuming that systemic treatment ?will take care of the brain? is dangerous....association of previous advanced immunosuppression with prevalent and sustained impairment suggests that there may be a non-reversible component of neurological injury that tracks with systemic disease progression [24]. Furthermore, 21% developed HAND despite effective HAART (although the precise number who were aviremic is unclear) [24]. Similarly, in a cohort of individuals with AIDS, 21% of aviremic individuals (who also had undetectable CSF HIV RNA) progressed to HAD [25]. A third prospective study also identified HAND in 8?34% (depending on the time point of the assessment) of aviremic patients without comorbidities and with a nadir CD4 cell count less than 200 cells/μl [26]......Identified risk factors for HAND include a high HIV viral set point, lower CD4 cell counts [27], anemia, low body mass index, increasing age, systemic symptoms [27,28], injection drug use [29], and female sex"



AIDS:

1 June 2010 - Volume 24 - Issue 9 - p 1367?1370




McArthur, Justin C; Brew, Bruce J

aDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

bDepartment of Neurology, St Vincent's Hospital, Darlinghurst, New South Wales, Australia.



The neurocognitive disorders associated with HIV (HAND) remain among the most common clinical disorders encountered in people infected with HIV, even in an era in which potent antiretroviral therapy is widely deployed. HAND is currently considered to encompass a hierarchy of progressively more severe patterns of central nervous system (CNS) involvement ranging from asymptomatic neurocognitive impairment (ANI), to minor neurocognitive disorder (MND), to the more severe HIV-associated dementia (HAD) [1]. With the improved survival of individuals treated with antiretrovirals, comorbid conditions have become increasingly salient, including particularly coinfection with hepatitis C and the effects of aging. Treatment guidelines for preferred initial antiretroviral regimens and for second or salvage regimens are essentially silent on the approach to HAND. For example, HIV-nephropathy is one indication for initiation of HAART, yet inexplicably HAND is not, unless it is severe enough to manifest as dementia. Brain penetration is crucial to achieve the goal of maximal suppression of HIV replication. Cerebrospinal fluid (CSF) antiretroviral concentrations are generally much lower than plasma concentrations, particularly for the protease inhibitors, and active efflux pumps, such as the P-glycoprotein may eliminate this class of drug [2]. An index of the CNS penetration of antiretrovirals can differentiate HAART regimens by their theoretical CNS penetration [3] and specific combinations have better brain penetration or greater efficacy in reversing HAND's deficits or suppressing CSF HIV RNA [4?7]. It remains uncertain whether individuals who have had prolonged aviremia can develop HAND. The study by Simioni et al. [8] sheds new light on this question by studying individuals with long-duration aviremia. It also raises concerns about the adequacy of current screening techniques for HAND. In their study, HAND was diagnosed in a high proportion of 200 long-duration (several years) aviremic individuals. The overall prevalence of cognitive complaints was 27%. The prevalence of HAND was 84% among patients with cognitive complaints and 64% in those without. ANI was found in 24%, MND in 52%, and HAD in 8%. HAND was more common in women, those with lower premorbid IQ (as measured by NART scores), or with neuropsychiatric symptoms.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #148 on: June 02, 2010, 03:44:17 PM »
The role of cytology (Pap tests) and human papillomavirus testing in anal cancer screening



AIDS:

1 June 2010 - Volume 24 - Issue 9 - p 1307?1313



Salit, Irving E; Lytwyn, Alice; Raboud, Janet; Sano, Marie; Chong, Sylvia; Diong, Christina; Chapman, William; Mahony, James B; Tinmouth, Jill

aHealth Network, Toronto General Hospital, Canada

bUniversity of Toronto, Toronto, Canada

cHenderson Hospital, Canada

dMcMaster University, Hamilton, Canada

eSt. Joseph's Hospital, Toronto, Canada

fSt. Joseph's Healthcare, Hamilton, Canada

gSunnybrook Medical Centre, Toronto, Ontario, Canada.



Abstract




Objective: To assess anal oncogenic human papillomavirus (HPV) and anal cytology as screening tests for detecting high-grade anal intraepithelial neoplasia (AIN 2+), as this is an immediate anal cancer precursor.




Design: Cross-sectional study of 401 HIV-positive men who have sex with men (MSM). The endpoint was histologically confirmed AIN 2+ obtained by high-resolution anoscopy. Cytology and biopsy specimens were assigned random numbers and independently assessed by two pathologists.




Methods: We did concomitant anal cytology, anal HPV testing and HRA with directed biopsies without knowing the results of each intervention. The main outcome measures were the sensitivity, specificity, negative predictive value and positive predictive value of anal cytology and oncogenic HPV for the detection of AIN 2+.




Results: Cytology was abnormal in 67% of patients: high-grade squamous intraepithelial lesion, 12%; low-grade squamous intraepithelial lesion, 43% and atypical squamous cells of undetermined significance, 12%. Biopsies were abnormal in 68% of patients: AIN 2+, 25% and AIN 1, 43%. HPV was detected in 93% with multiple HPV types in 92% and oncogenic HPV types in 88%. Test performance characteristics for the detection of AIN 2+ using any abnormality on anal cytology were: sensitivity 84%, specificity 39%, negative predictive value 88% and positive predictive value 31%; using oncogenic HPV: sensitivity 100%, specificity 16%, negative predictive value 100% and positive predictive value 28%.




Conclusion: Anal cytology and HPV detection have high sensitivity but low specificity for detecting AIN 2+. HIV-positive men who have sex with men have a high prevalence of AIN 2+ and require high-resolution anoscopy for optimal detection of high-grade anal dysplasia.

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #149 on: June 02, 2010, 03:45:00 PM »
Rosiglitazone improves lipoatrophy in patients receiving thymidine-sparing regimens



AIDS:

1 June 2010 - Volume 24 - Issue 9 - p 1291?1298



Tungsiripat, Marisa; Bejjani, Dalia El; Rizk, Nesrine; O'Riordan, Mary Ann; Ross, Allison C; Hileman, Corrilynn; Storer, Norma; Harrill, Danielle; McComsey, Grace A

aCleveland Clinic, USA

bMetrohealth Medical Center, USA

cCase Western Reserve University, and University Hospitals Case Medical Center, Cleveland, Ohio, USA.



Abstract




Objective: Thymidine reverse transcriptase inhibitors (tNRTI) are strong inhibitors of PPAR-γ and clearly implicated as a cause of lipoatrophy. Thiazolidenediaones (TZD), potent PPAR-γ agonists, would be expected to be beneficial in HIV lipoatrophy, but prior studies have been conflicting. None specifically excluded the use of tNRTIs. We report the first study in individuals treated with tNRTI-sparing regimens using a TZD for treatment of HIV lipoatrophy.




Design: This double-blind, placebo-controlled study evaluated limb fat in HIV-infected individuals with lipoatrophy who discontinued tNRTI at least 24 weeks prior to enrollment.




Methods: Individuals were randomized to rosiglitazone vs. placebo for 48 weeks. Dual energy X-ray absorptiometry (DEXA)-scans and fasting metabolic assessments were serially performed.




Results: We enrolled 71 individuals, 17% were female and 51% white. Baseline characteristics were similar between groups except for higher total cholesterol in the placebo group (P = 0.04). At 48 weeks, limb fat (grams) increased significantly (P = 0.02) more in the rosiglitazone than in the placebo group: median (IQR) 448 (138, 1670) vs. 153 (−100, 682), respectively. Of lipids parameters, only total cholesterol increased significantly more in the rosiglitazone group (P = 0.008). Prevalence of metabolic syndrome and total bone mineral density did not change between or within groups.




Conclusion: In the absence of tNRTI, rosiglitazone significantly improves lipoatrophy without deleterious effect on bone mineral density. Total cholesterol, but not triglycerides, significantly increased in the rosiglitazone arm. The glitazones may be a promising addition for accelerating fat recovery in individuals who had switched off tNRTI and remain with significant lipoatrophy.

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #150 on: June 02, 2010, 03:55:39 PM »
White House HIV/AIDS office again opens the floor -- and phones -- for community input
by Yusef Najafi
Published on  May 20 2010


The White House Office of National AIDS Policy (ONAP) presented a tentative outline of a National HIV/AIDS Strategy during a community meeting in D.C. and a national conference call on Friday, May 14.


''What we're telling you is where we're at, but I think we can all recognize that this will evolve,'' said ONAP Director Jeffrey Crowley, addressing the crowd of about 60 people in the South Court Auditorium of the Eisenhower Executive Office Building.

ONAP reps (l-r): senior program manager James Albino, senior policy advisor Gregorio Millett, director Jeffrey Crowley and policy advisor Adelle Simmons.
(Photo by Yusef Najafi)


The 72-page booklet distributed at the meeting, ''Community Ideas for Improving the Response to the Domestic HIV Epidemic,'' provided the outline that was crafted after ONAP conducted an Internet survey on its website, as well as hosted 14 community discussions around the country, including one at the University of D.C. on Sept. 21, 2009.


The work-in-progress strategy is broken down into three components: prevent new HIV infections, increase access to care and optimize health outcomes, and reduce HIV-related health disparities.


''We can evolve based on what we hear today, but also as we continue engaging with the [Presidential Advisory Council on HIV/AIDS (PACHA)] and also our federal partners,'' Crowley added, later opening up the floor to comments from the audience.


''What we hear today is not set in stone, but we want to give you an update that will really signal the direction that we're moving in.''


Jen Heitel Yakush, director for public policy at the Sexuality Information and Education Council of the United States (SIECUS), based in D.C., attended the meeting and said comprehensive sex education is key.


''We need to be talking about HIV prevention and STI prevention in addition to unintended pregnancy prevention, and the inter-related health needs of particularly LGBT young people,'' Yakush, who is bisexual, told Metro Weekly immediately following the hearing.


''I have a lot of hope for the National HIV/AIDS Strategy,'' she added. ''We know that it's going to be broad strokes. I hope there's going to be some detailed goals and measurements within the National HIV/AIDS Strategy. We also know that even in these tight fiscal times we need increased funding if we're really going to have an impact on the number of new HIV infections every year.''


Among other local attendees was Don Blanchon, CEO of the Whitman-Walker Clinic, though he did not speak at the event.


For more information about the Office of National AIDS Policy, visit whitehouse.gov/administration/eop/onap/.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #151 on: June 02, 2010, 03:57:11 PM »
http://www.eurekalert.org/pub_releases/2010-06/sri-srs060110.php


Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute

Scripps research scientists determine structure of immune molecule that counteracts HIV strains
The findings advance the effort to develop an AIDS vaccine
LA JOLLA, CA ? June 1, 2010 ?In findings that contribute to efforts to design an AIDS vaccine, a team led by Scripps Research Institute scientists has determined the structure of an immune system antibody molecule that effectively acts against most strains of human immunodeficiency virus (HIV), the virus that causes AIDS.

The study, which is being published in an advance, online issue of the journal Proceedings of the National Academy of Sciences (PNAS) during the week of June 1, 2010, illuminates an unusual human antibody called PG16.

"This study advances the overall goal of how to design an HIV vaccine," said Scripps Research Professor Ian Wilson, who led the team with Dennis Burton, Scripps Research professor and scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center at Scripps Research. "This antibody is highly effective in neutralizing HIV-1 and has evolved novel features to combat the virus."

The Problem with HIV

According to the World Health Organization's latest statistics, around 33 million people are living with HIV worldwide. During 2008 alone, more than 2 million men, women, and children succumbed to the disease and an estimated 2.7 million were infected with HIV. One of the most compelling medical challenges today is to develop a vaccine that will provide complete protection to someone who is later exposed to this virus.

HIV causes AIDS by binding to, entering, and ultimately leading to the death of T helper cells, which are immune cells that are necessary to fight off infections by common bacteria and other pathogens. As HIV depletes the body of T helper cells, common pathogens can become potentially lethal.

An effective HIV vaccine would induce antibodies (specialized immune system molecules) against the virus prior to exposure to the virus. Also called immunoglobulins, these antibodies would circulate through the blood, and track down and kill the virus.

Most of the antibodies that the body produces to fight HIV, however, are ineffective. The surface of the virus is cloaked with sugar molecules that prevent antibodies from slipping in and blocking the proteins the virus uses to latch onto a cell and infect it. To make matters more complicated, HIV is constantly mutating, so there are multiple HIV strains that antibodies elicited in any vaccine must be able to sense and destroy.

Nonetheless, while rare, broadly neutralizing antibodies against HIV do exist.

Last year, a team of scientists from IAVI, Scripps Research, Theraclone Sciences, and Monogram Biosciences published research from a systematic search for such antibodies among 2,000 volunteers. The study revealed two powerful new broadly neutralizing antibodies against HIV?PG9 and PG16, isolated from a volunteer in Africa.

"Hammerhead" Structure

Once the broadly neutralizing antibodies were discovered, the next challenge was to figure out how they worked. To shed light on this question, in the current study members of the Wilson lab turned to x-ray crystallography, a technique that can solve structures to exquisitely high resolution.

In x-ray crystallography, scientists manipulate a protein or some other molecule so that a crystal forms. This crystal is then placed in front of a beam of x-rays, which diffract when they strike the atoms in the crystal. Based on the pattern of diffraction, scientists can reconstruct the shape of the original molecule. The scientists succeeded in forming crystals of the active part of the PG16 antibody, and in reconstructing the structure from the data?with some surprising results.

"The antibody has a novel and really interesting subdomain that hasn't been seen before," said Research Associate Rob Pejchal, who is first author of the paper. "This subdomain, which we found plays a major role in the recognition and neutralization of HIV, has a different kind of antibody architecture. We like to call it the 'hammerhead' because it resembles the head of a hammerhead shark. It reaches out from the main part of the antibody and it has two flat ends on top."

Co-author Laura Walker, a graduate student in the Scripps Research Kellogg School of Science and Technology, added, "This hypervariable loop (CDR3) that forms the novel subdomain is also unusually long for an antibody. Almost all of the antibodies we know to be broadly neutralizing against HIV have one unusual feature or another."

Pejchal notes that the study also revealed that PG16 was sulfated, suggesting possible mechanisms of action not usually seen in antibodies this effective against HIV.

While the scientists were unsuccessful so far in crystallizing PG16's sister molecule PG9, they were able to glean insight into its action from biochemical studies using both molecules. By switching a small (seven-amino acid) segment of the CDR3 subdomain of PG9 for a similar segment from PG16, the team changed the subset of HIV isolates neutralized by the antibody. This confirmed the loop in question was the "business end" of the antibody and suggested that it might be possible to create other interesting variants of the antibody by manipulating this region.

Seth Berkley, president and CEO of IAVI, which funded the study with the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH), noted, "These studies of PG16 have taught us a lot about how these neutralizing antibodies work. I am particularly excited by the possibilities these findings open up for AIDS vaccine development, since the breadth and potency of HIV neutralization achieved by PG16 is what we'd like to see in the antibodies elicited by a vaccine. IAVI and its researchers will continue to support the application of these findings to the design of novel immunogens against HIV. We hope that we will be able to translate the insights gleaned from this study into the design of a promising AIDS vaccine candidate."


###

In addition to Wilson, Burton, Pejchal, and Walker, authors of the paper, "Crystal structure and functional studies of broadly reactive antibody PG16 reveal a novel H3 subdomain that mediates potent neutralization of HIV-1," are Robyn Stanfield and Pascal Poignard of Scripps Research and IAVI, Wayne Koff and Sanjay Phogat of IAVI New York. This study was supported by IAVI, NIAID, the Skaggs Institute of the Scripps Research Institute, and the Ragon Institute.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is located in Jupiter, Florida.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #152 on: June 11, 2010, 04:38:32 PM »
Getting Pregnant With HIV+ Husband. Barrier to Sperm Washing in California, A perilous road to reproduction


The Calif governor’s surprising veto of a fertility-procedure bill means HIV-discordant couples must risk their own health in order to conceive.
By Katie Worth, Illustration by Matthew Hollister

July 1 2010, http://www.sanfranmag.com
This month, for the first time in her eight-year marriage, Deanna Crandell plans to have unprotected sex with her husband. It’s not a decision she made lightly: Her husband is HIV-positive and she is not, so the consequences could be grave. But Crandell, 34, is desperate to have a baby, and her only other option is a fertility procedure that most clinics aren’t willing to perform, despite the fact that it’s been legal in California for more than two years.

The method, called “sperm washing,” separates potentially infected semen from healthy sperm cells, making fertility treatments like in-vitro fertilization and intrauterine insemination safe for HIV-discordant couples like the Crandells. Until 2007, it was illegal in California because of an 18-year-old law that prohibited transferring tissue from an HIV-infected person to a healthy individual. But studies in the United States and Europe had recorded more than 4,500 successful sperm-washing inseminations without a single case of HIV transmission—so San Francisco state senator Carole Migden drafted a bill that would allow clinics to perform the procedure. It breezed through the state legislature and was signed by Governor Schwarzenegger.

Before advocates could celebrate, though, it became clear that the law contained at least one fatal flaw: It required the clinic that performed the procedure to provide post-treatment care, like administering antiretroviral drugs to further reduce a woman’s chances of contracting HIV. Most fertility specialists haven’t been trained in HIV care, so they’ve been reluctant to take on this responsibility—in fact, only one clinic in California offers the procedure.

In an effort to mend the ineffectual law, state assemblymember Jerry Hill, of San Mateo County, introduced a bill that essentially relieved clinics of the burden to provide post-treatment care. It was unanimously approved by the legislature and sent to the governor’s desk in September 2009. But something unexpected happened: Schwarzenegger vetoed it. He said he supported “the intent” of the bill, but he thought it would inappropriately restrict the California Department of Public Health. Senator Hill was struck dumb, especially since he had vetted the bill with the governor’s office and the CDPH, and neither had raised any red flags. “Families are running out of time here,” Hill says.

The Crandells, for instance, are no longer willing to wait. While they’ve saved enough money to be able to pay for the fertility procedure if it were offered locally, the couple cannot sustain repeated trips either out of state or to Los Angeles (where California’s only clinic willing to carry out HIV sperm washing is located) for the insemination plus the requisite follow-up appointments. So in October, Crandell met with doctors to prepare for her first attempt at timed unprotected sex. She knows she faces the possibility of contracting HIV (by one analysis, a 4.3 percent chance), but she feels it’s worth the risk. “We’ve been married for eight years,” she says. “We were ready to have kids eight years ago, and we’re more than ready now.”
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Offline red_Dragon888

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« Reply #153 on: June 13, 2010, 05:38:58 PM »
http://beforeitsnews.com/news/77/570/OU_Researchers_Develop_First_T-Cell_Vaccine;_Implications_for_West_Nile_Virus,_Cancer,_HIV_Hepatitis.html

OU Researchers Develop First T-Cell Vaccine; Implications for West Nile Virus, Cancer, HIV & Hepatitis

Powered by TranslateContributed by Alton Parrish (Editor)
Saturday, June 12, 2010 1:24
More stories from this contributorThis story has been viewed 80 times
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1 person on this page right nowResearchers at the University of Oklahoma Health Sciences Center have found a way, for the first time, to create a vaccine using a protein that activates a distinct part of the immune system. The research has potential treatment and prevention applications for several viral diseases, cancer, tuberculosis and HIV.

The work appears in a recent issue of The Journal of Immunology.

"No one has ever done this with a T-cell vaccine, so we’re learning; but now we are starting to get some traction. We are finding that a T-cell vaccine can work," said William Hildebrand, Ph.D., the lead researcher on the project.

For years, Hildebrand and his research team have been working with the body’s alarm system to learn how cells alert the immune system that something is wrong. The goal is to create viable targets for vaccines that activate T-cells in the immune system. T-cells are responsible for killing virus-infected cells in your body. T-cells also kill cells that become cancerous. Some vaccines such as the smallpox vaccine activate T-cells, but this occurs inadvertently. Until now, vaccines have focused on generating antibodies to keep you from getting sick.

While many of these antibody (B-cell) vaccines work well, the dependence on antibodies has prompted some viruses to skirt antibody immunity, making vaccines less effective or not effective at all for some viruses. With a T-cell vaccine, researchers would be able to activate another arm of the immune system to target a specific virus in the body and kill it.

To develop the vaccine, Hildebrand began by determining how the immune system distinguishes between a virus-infected or cancerous cell and a healthy cell. Researchers determine what unique proteins are sent to the surface of the infected cell to provide T-cells with an optimal target. Different viruses send different proteins.

Researchers started with West Nile virus since West Nile doesn’t change like the flu or develop resistance like cancer or HIV. After developing the target over several years, researchers at the OU Health Sciences Center worked with colleagues at Washington University in St. Louis to create a vaccine.

The process is now being repeated for targets and vaccines in other areas, such as cancer, where activating T-cells is difficult.

"Now that we have demonstrated the feasibility of developing a T-cell-specific vaccine, we intend to use the same process to discover other reliable targets, validate them and develop additional vaccines," Hildebrand said.

The research is funded by grants and contracts totaling $15 million from the National Institutes of Health.



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Re: http://natap.org/
« Reply #154 on: June 15, 2010, 05:00:58 PM »
http://www.pharmacynews.com.au/article/australian-researchers-pave-way-for-new-vaccine/518833.aspx

Australian researchers pave way for new vaccine
15 June 2010 | by Nick O'Donoghue    .Results of research carried out by the University of Sydney could help develop a vaccine to prevent Herpes Simplex Virus (HSV).   

Findings published in the Journal of Immunology identified how skin cells are infected by the virus, which is associated with the promotion and transmission of Human Immunodeficiency Virus (HIV).   

Lead investigator Associated Professor Cheryl Jones said HSV was a medically significant virus that caused devastating disease throughout life for sufferers.   

“Potentially, we may be on the right track for a new discovery.   

“The skin represents a major entry point; therefore understanding how immune cells behave during the infection is of vital importance to researchers trying to find a cure for HSV.   

“HSV infection of the skin and genital mucosa are important for the promotion and transmission of HIV, the virus that causes AIDS,” she said.   

The research carried out in mice found HSV can infect and kill Langerhans cells, the immune cell in the top layer of the skin, which should exit the skin to the lymph nodes to trigger a stronger immune response to infection.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #155 on: June 17, 2010, 07:08:52 AM »
_______________________________________________

Treatment Cuts HIV Transmission from Mother to Child




MedPage Today

Published: June 16, 2010




Perinatal transmission of HIV, including during breast-feeding, can be markedly reduced by antiretroviral therapy, either of mothers or their infants.




That's the message from two randomized trials in Africa that compared various ways of using antiretroviral medications to prevent perinatal transmission, both reported in the June 17 issue of the New England Journal of Medicine.




Despite differences between the trials, taken together they imply that "it should be possible to eliminate new perinatal HIV-1 infections globally" with the appropriate use of the medications, said Lynne Mofenson, MD, of the NIH.

Action Points 




    * Explain to interested patients that these studies suggest that a range of interventions can reduce the risk that HIV-positive mothers will pass the virus to their newborns.




In an accompanying editorial, Mofenson argued that debate over which regimen is best "should not be used to justify inaction."




Instead, Mofenson said, the choice of regimen is secondary to identifying, caring for, and treating HIV-positive women and their infants.




The two trials used different medications, took place in different countries, and had differing goals.




A study in Malawi, led by Charles van der Horst, MD, of the University of North Carolina in Chapel Hill, looked at the breast-feeding period and asked whether treating the mother or the infant would have better results.




In Botswana, a team led by Roger Shapiro, MD, of Beth Israel Deaconess Medical Center in Boston, compared the effects on transmission of two regimens of maternal triple-drug therapy starting in the third trimester and extending during a six-month breast-feeding period.




In the Malawi study, all mothers and children got the now-standard perinatal prophylaxis of a single dose of nevirapine (Viramune) and a week of nevirapine and lamivudine (3TC). The 2,369 HIV-positive breast-feeding mothers all had a CD4-positive lymphocyte count of at least 250 cells per cubic millimeter and thus -- by then-current standards -- did not require antiretroviral therapy.




After the perinatal intervention, they were randomly assigned to no further treatment (the control group), to maternal therapy with a triple-drug regimen, or to infant treatment with nevirapine. The intervention period lasted 28 weeks.




The researchers found:




    * 5% of infants were HIV-positive at two weeks.

    * The estimated risk of HIV transmission between then and the end of the study period was 5.7% in the control group, compared with 2.9% in the maternal-regimen group (difference significant at P=0.009), and 1.7% in the infant-regimen group (significant at P<0.001).

    * The estimated risk of the combined endpoint of infant HIV infection or death in the same period was 7.0% in the control group, 4.1% in the maternal-regimen group (difference significant at P=0.02), and 2.6% in the infant-regimen group (significant at P<0.001).

    * 6.2% of women getting antiretroviral therapy suffered from neutropenia, compared with 2.6% of those whose infants were treated and 2.3% in the control group.

    * 1.9% of the infants receiving nevirapine had a hypersensitivity reaction to the drug.




In the Botswana study, 560 pregnant HIV-positive women with a CD4 cell count of at least 200 per cubic millimeter were randomly assigned to get one of two triple-drug regimens, starting between 26 and 34 weeks gestation.




One group (dubbed the nucleoside reverse-transcriptase inhibitor [NRTI] group) got coformulated abacavir (Ziagen), zidovudine (AZT), and lamivudine, while the other (the protease-inhibitor group) got lopinavir-ritonavir (Kaletra) as well as zidovudine and lamivudine.




The control group consisted of 170 women with CD4 counts less than 200 cells per cubic millimeter who were treated with nevirapine, zidovudine, and lamivudine.




All infants got a single dose of nevirapine perinatally, followed by four weeks of zidovudine.




The researchers found:




    * Viral control -- less than 400 copies of HIV RNA per milliliter -- did not differ significantly among the groups at delivery: 96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the control group.

    * Viral control remained high and did not differ throughout the breast-feeding period: 92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the control group.

    * By six months, eight of the 709 live-born infants (1.1%) were infected. Six were infected in utero (four in the NRTI group, and one each in the other groups), and two were infected during breast-feeding (both in the NRTI group).

    * Side effects that limited treatment were seen in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the control group.




Although the trials can't be compared directly because of their different designs, Mofenson said some lessons can be learned.




One such lesson, she said, is that antiretroviral regimens aimed at preventing transmission should start during pregnancy. In the Malawi study, which did not treat women during pregnancy, in utero transmission was 5%, compared with 0.9% in the Botswana study.




The Malawi study also showed that highest risk for transmission was early in the breast-feeding period; during that period, the infant regimen reduced transmission by 86.1% (compared with the control group) and the maternal regimen reduced transmission by 52.8%.




The difference, Mofenson said, is probably a factor of the time the maternal regimen took to have an effect, suggesting that infant treatment is likely to be more important if the mother presents late in her pregnancy or during labor.




The Malawi study was supported by the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the University of North Carolina Center for AIDS Research, the NIH Fogarty AIDS International Training and Research Program, Abbott Laboratories, GlaxoSmithKline, Boehringer Ingelheim, Roche Pharmaceuticals, Bristol-Myers Squibb, the Elizabeth Glaser Pediatric AIDS Foundation, the United Nations Children's Fund, the World Food Program, the Malawi Ministry of Health and Population, Johnson & Johnson, and the U.S. Agency for International Development.




Van der Horst reported financial links with Abbott Laboratories and GlaxoSmithKline.




The Botswana study was supported by the National Institute of Allergy and Infectious Diseases and the Fogarty International Center.




Shapiro reported that Abbott Laboratories and GlaxoSmithKline supplied study drugs, but reported no other potential conflicts.




Mofenson made no disclosures.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #156 on: June 24, 2010, 02:05:03 PM »
NATAP http://natap.org/
_______________________________________________

Diet Soft Drinks Deplete Urinary Calcium



MedPage Today

Published: June 22, 2010




Action Points 




    * Explain to interested patients that this study suggests that drinking diet colas may be associated with a negative calcium balance, leaving people at risk for fracture.







    * Note that this was a very small study, presenting data from just 16 women.







    * Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.




SAN DIEGO -- Drinking too many diet soft drinks may result in a negative calcium balance, a marker of low bone mineral density, researchers here reported.




Mean calcium excretion over three hours after drinking diet cola was 6.85 mg higher than after drinking water (P=0.004)