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Author Topic: John2038's Research News  (Read 202004 times)

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Offline John2038

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Re: John2038's Research News
« Reply #200 on: December 11, 2008, 03:49:31 AM »
Cancer to be world's top killer by 2010, WHO says

Few are aware that cancer already kills more people in poor countries than HIV, malaria and tuberculosis combined.

Rising tobacco use in developing countries is believed to be a huge reason for the shift, particularly in China and India, where 40 percent of the world's smokers now live.

So is better diagnosing of cancer, along with the downward trend in infectious diseases that used to be the world's leading killers.

Cancer diagnoses around the world have steadily been rising and are expected to hit 12 million this year. Global cancer deaths are expected to reach 7 million, according to the new report by the World Health Organization.

An annual rise of 1 percent in cases and deaths is expected — with even larger increases in China, Russia and India. That means new cancer cases will likely mushroom to 27 million annually by 2030, with deaths hitting 17 million.

Underlying all this is an expected expansion of the world's population — there will be more people around to get cancer.

By 2030, there could be 75 million people living with cancer around the world, a number that many health care systems are not equipped to handle.

"This is going to present an amazing problem at every level in every society worldwide," said Peter Boyle, director of the WHO's International Agency for Research on Cancer.

Boyle spoke at a news conference with officials from the American Cancer Society, the Lance Armstrong Foundation, Susan G. Komen for the Cure and the National Cancer Institute of Mexico.

The "unprecedented" gathering of organizations is an attempt to draw attention to the global threat of cancer, which isn't recognized as a major, growing health problem in some developing countries.

"Where you live shouldn't determine whether you live," said Hala Moddelmog, Komen's chief executive.

The organizations are calling on governments to act, asking the U.S. to help fund cervical cancer vaccinations and to ratify an international tobacco control treaty.

Concerned about smoking's impact on cancer rates in developing countries in the decades to come, the American Cancer Society also announced it will provide a smoking cessation counseling service in India.

"If we take action, we can keep the numbers from going where they would otherwise go," said John Seffrin, the cancer society's chief executive officer.

Other groups are also voicing support for more action.

"Cancer is one of the greatest untold health crises of the developing world," said Dr. Douglas Blayney, president-elect of the American Society of Clinical Oncology.

"Few are aware that cancer already kills more people in poor countries than HIV, malaria and tuberculosis combined. And if current smoking trends continue, the problem will get significantly worse," he said in a written statement.


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Offline John2038

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Re: John2038's Research News
« Reply #201 on: December 11, 2008, 04:16:20 AM »
NATAP News

Targeting HIV Entry: 4th Interntnl Wrkshp

Low Enfuvirtide and Maraviroc Penetration of CSF--and CSF Resistance to Enfuvirtide
A case report from the University Medical Center Utrecht documented low levels of the entry inhibitors enfuvirtide and maraviroc in cerebrospinal fluid (CSF) despite adequate levels in plasma and undetectable plasma viremia. Virus resistant to enfuvirtide, but not to maraviroc, could be detected in CSF of this salvage therapy patient.
A 50-year-old man with multidrug-resistant virus began a rescue regimen including the fusion inhibitor enfuvirtide (90 mg once daily), the CCR5 antagonist maraviroc (300 mg twice daily), and reverse transcriptase inhibitors tenofovir plus zidovudine and lamivudine coformulated as Combivir. Presalvage genotyping disclosed no enfuvirtide-related mutations in gp41, and the Trofile assay determined that the virus used the CCR5 coreceptor. After a months-long drop in plasma viremia, the viral load eventually did fall below 50 copies and remained undetectable for 8 months. At that point clinicians performed a spinal tap in an attempt to diagnose neurologic symptoms.
Although viral load remained undetectable in plasma, two CSF samples had detectable loads of 2780 and 1490 copies. Adding darunavir/ritonavir to the regimen pushed CSF loads below the limit of detection. Plasma concentrations of enfuvirtide and maraviroc were adequate at 3.74 and 0.146 micrograms/mL, but CSF levels of both drugs were low: 0.055 micrograms/mL for enfuvirtide and only traces of maraviroc below the limit of detection. CSF levels of darunavir were low but detectable.
...

Vicriviroc Phase 3 Trial and Naive Study May Afford New Angle on Role of CCR5 Blockers
Phase 3 trials of vicriviroc, the CCR5 antagonist that works best in a ritonavir-boosted regimen, are fully enrolled. And some baseline data suggest differences between this phase 3 study population and those in recent salvage trials could afford further insights into the eventual role of CCR5 antagonists. But those differences may also make the results harder to interpret. At the same time Schering's Lisa Dunkle offered a new analysis of pooled results from phase 2 trials, issued an update on cancer incidence among vicriviroc takers, and outlined a novel trial of this CCR5 antagonist in previously untreated people.
...
The surprise development of cancer in 6 people taking vicriviroc and 2 taking placebo in ACTG 5211 ignited fears that plugging CCR5 coreceptors somehow touches off malignancies. Summarizing cancer reports among vicriviroc takers through June 2008, including 600 person-years of vicriviroc exposure, Dunkle counted only a handful of additional cancer cases as use of the drug soared. Except for a single early report of gastric carcinoma, all malignancies have been lymphomas or cutaneous cancers. Malignancies per 100 person-years peaked in June 2006 at around 6 and dropped to around 3 by June 2008.
...

Almost 40% of Viruses in Treatment-Experienced German Group Use CXCR4
Testing coreceptor use with the enhanced Trofile assay, German investigators determined that nearly 40% of viruses isolated from treatment-experienced people could use the CXCR4 coreceptor, a result meaning CCR5 antagonists will not help much in controlling these patients' viral replication. As in earlier studies, a gene-based algorithm used to predict coreceptor use had high specificity but relatively low sensitivity in yielding the same results as Trofile. Contrary to other studies, however, the German survey found that genotyping predicted Trofile-determined coreceptor use better in people with a non-B HIV-1 subtype than in people infected with subtype B virus.
...

Neurological/Cognitive Impairment on HAART: 50% on HAART have cognitive impairment
"As HIV practitioners, we must be aware of possible ongoing disruption of neurocognitive function in our patients who otherwise appear to be doing well and to the potential for HIV-related neurologic damage in the HIV-infected population as a whole. Optimization of HIV therapy in this regard may include starting antiretroviral treatment early enough to avoid neuronal loss and using viral control in the CNS as an efficacy measure. Good CNS penetration does not appear to have been a goal of recent antiretroviral drug development, and we need to support efforts to decide if brain penetration is a crucial component in the design of therapy. We should also encourage further research to develop effective means to protect the brain from alternate pathways of damage. New therapies for amyloid toxicity are being developed, and these may eventually play a role in the treatment of HIV-associated dementia."
...

ICAAC


AIDS-Defining Conditions (ADCs) in the BENCHMRK -1 and -2 Trials: 48 Week Analysis
In the BENCHMRK studies, the rates of clinical endpoints occurring during the double-blind phase were lower for raltegravir compared with placebo at week 48, regardless of endpoint. These differences did not reach statistical significance.
Esophageal candidiasis was the most frequent ADC in both treatment groups.
Advanced disease (low CD4 counts, high HIV RNA levels, and previous ADC) rather than treatment history or GSS appeared to be associated with disease progression and/or death.
Patients who experienced an ADC or died showed lower responses for HIV RNA suppression and smaller CD4 cell increases than patients who did not.
The BENCHMRK studies are ongoing and will provide an opportunity for further analysis at time points beyond week 48.


Studies


ddi + hydroxyurea making comeback
...
A new concept of combining drugs with antiviral properties with those that act directly on the T cell target of HIV is emerging._These combinations of drugs are called "ViroStatic" as they combine anti viral and cytostatic mechanisms to inhibit viral replication.__
Virostatic combinations are being investigated to restrict virus target populations (CD4+ T lymphocytes), target viral reservoirs, and possibly restore immune functions by reducing excess immune activation - a fundamental component of HIV/AIDS pathogenesis.__
Cytostatic drugs such as hydroxyurea, mycophenolic acid, leflunomide and rapamycin utilize multiple novel mechanisms of action to impede HIV by targeting host cellular proteins that are not susceptible to mutation. Therefore, their resistance profile appears to be quite favorable. Since many of these drugs act by inhibiting the synthesis of deoxynucleotides, essential for HIV reverse transcription, they also favor the incorporation of nucleoside analogues into viral DNA, thus synergizing with the antiviral activity of currently used nucleoside reverse transcriptase inhibitors (NRTIs).
...

Nut-Enriched Mediterranean Diet Helps Reverse Metabolic Syndrome
A non-energy-restricted traditional MedDiet enriched with nuts, which is high in fat, high in unsaturated fat, and palatable, is a useful tool in managing the MetS (metabolic syndrome)
In this clinical trial, older participants at high risk for developing CVD who consumed a non-energy-restricted, traditional Mediterranean-style diet supplemented with 1 daily serving of mixed nuts for 1 year showed a reduction in the overall prevalence of MetS (metabolic syndrome) compared with participants given advice on following a low-fat diet. Subjects in the MedDiet + VOO (olive oil) group showed a nonsignificant reduction in MetS prevalence. The beneficial effect of the MedDiet + nuts was more a consequence of higher rates of reversion among participants who had the MetS at baseline than of a lesser incidence among those not meeting criteria for the syndrome at baseline, and was independent of sex, age, baseline obesity status, or changes in body weight. These results provide further evidence of the potential benefit of healthy dietary patterns on MetS status.13-15 The novelty of our findings is that a positive effect on MetS was achieved by diet alone, in the absence of weight loss or increased energy expenditure in physical activity.
The traditional MedDiet is characterized by a high intake of cereals, vegetables, fruits, and olive oil; a moderate intake of fish and alcohol, mostly wine; and a low intake of dairy products, meats, and sweets.10 The MedDiet is a high-fat, high-unsaturated-fat food pattern because olive oil is used abundantly as culinary fat and for dressing dishes, which facilitates intake of substantial quantities of vegetables. Nuts are another high-fat, high-unsaturated-fat food commonly consumed in the MedDiet. Evidence from epidemiological and clinical studies suggests that regular nut intake might have a positive effect on adiposity, insulin resistance, and other metabolic disturbances linked to the MetS
...

Offline John2038

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Re: John2038's Research News
« Reply #202 on: December 11, 2008, 04:17:58 AM »
Charged with faking AIDS test for sex

An HIV-positive Queens man is facing jail time after allegedly faking a clean bill of health to persuade his girlfriend to have unprotected sex.

Duane Lang, 48, typed up an official-looking HIV test report from the AIDS Center of Queens, the city's Department of Investigation charged.

The report said that as of last Dec. 12, Lang was "negative/nonreactive for the HIV-1 antibody based upon the rapid HIV antibody test," investigators said.

Lang - who has been HIV-positive since 2002 - used to volunteer at the city-funded AIDS Center, authorities said.

"With deceit and depravity, the defendant repeatedly endangered the life of a person he supposedly cared for," DOI Commissioner Rose Gill Hearn said.

"Rarely have we seen a forged document used in a way that is so directly and personally destructive to another human being."

Lang was arrested Monday and charged with reckless endangerment and criminal possession of a forged document. He was released on his own recognizance and faces seven years in prison if convicted.

The victim had unprotected sex as many as 10 times at Lang's Richmond Hill apartment from December 2007 to March, authorities said. It was unclear if the unidentified woman contracted the virus.

The horrified victim finally got the truth about Lang's medical condition on March 19, when she questioned him about the authenticity of his test report, authorities said.

Lang admitted he was HIV-positive and the test was a fake, the criminal complaint says.

He told investigators the form was used as a demonstration on a retreat. He claimed he took it home to "rip it up ... and next thing he knew it was gone," prosecutors said.

The center's medical director, Dr. Marc Johnson, was listed on the bogus test report. His name was spelled wrong and there was no signature, the complaint says. The agency is not facing any charges.


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Offline John2038

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Re: John2038's Research News
« Reply #203 on: December 11, 2008, 04:19:30 AM »
Merck plans to push for expanded use of its Isentress AIDS med and the Gardasil

Merck plans to push for expanded use of its Isentress AIDS med and the Gardasil vaccine next year. In particular, the drugmaker will seek FDA approval to market the Gardasil HPV vaccine for women up to 45 years old and…men.

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Offline John2038

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Re: John2038's Research News
« Reply #204 on: December 11, 2008, 06:16:35 PM »
After Mbeki..

Bad news for HIV patients

No new patients will be put on antiretroviral medication in the Free State until the provincial health department's financial woes are sorted out, a department spokesperson said on Thursday.

Other chronic medicines would also run out due to the lack of money, Elke de Witt said.

"Stocks must run out if you do not have money to replenish them."

The department announced its financial problems on November 14.

"We have said it from the start that no new patients would be accommodated and only existing patients would be serviced."

De Witt said the department had had to make some tough decisions about its finances.

She said it was not known when the situation would change.

On November 12 the national health department announced steps to help the Free State's shortage of ARVs, caused by budget constraints.

Amongst the measures announced was the immediate transfer of R9,5-million to buy essential drugs for patients on the ARV programme.

The Volksblad newspaper reported on Thursday that some 170 medicines were out of stock at the Universitas Hospital in Bloemfontein.

These included medicines to treat TB, asthma, epilepsy, high blood pressure and hypertension and some antibiotics.

The Free State health department had issued a circular telling hospital personnel to do only "absolutely essential services".

"The department acknowledges that due to the possible non-treatment of patients and lack of stock it might face legal action," the report read.

The health department would take full responsibility in such cases, the report noted.

De Witt said government officials were "working very hard" to solve the financial problems.

"A lot of people (officials) are very worried. The situation is seen as very serious by all the stakeholders."

The provincial health department's cost containment measures, announced on November 25, would be in effect until the end of January 2009.

The measures were applicable in 31 hospitals, clinics and administrative offices in the province.

They included the postponement of all routine, non-emergency surgical cases until the end of January 2009. Any patients that could, would be discharged.

All privately-funded patients would be redirected to private medical facilities. Public hospitals would only accept emergency referrals from other institutions and other provinces.

Staff would also be given mandatory leave.

All non essential meetings, including "non-critical appointments", were cancelled. - Sapa


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Offline John2038

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Re: John2038's Research News
« Reply #205 on: December 11, 2008, 06:18:34 PM »
Individual’s DNA sets time clock for HIV to turn into AIDS

A new study has revealed how quickly HIV turns into AIDS might depend on an individual’’s DNA.

In the study, Stephen O”Brien from the National Cancer Institute in Frederick, Maryland, and colleagues found that some variations in the DNA in mitochondria, the parts of cells that generate energy, seem to make AIDS develop twice as fast as others.

For the study, they examined data from five long-term studies tracking a total of 1833 people with HIV during the 1980s and early 1990s.

This was before antiretroviral therapy (HAART) was commonly used, so the team could follow the disease’’s development without intervention.

By examining the time it took for the subjects to develop AIDS-related diseases and linking it to their genetic information, the researchers found that some mitochondrial DNA genotypes are linked to rapid development of AIDS.

For example, subjects with specific sets of variations known as U5a1 and J haplogroups progressed to AIDS at twice the average rate of the studied population. On contrary, people with the H3 haplogroup progressed less than twice as slowly.

This supports existing theories that mitochondria are implicated in the progression of HIV/AIDS.

The virus kills immune cells by triggering cell suicide, which appears to happen more easily in cells with mitochondria that generate less energy.

“Having less energy available seems to exacerbate the effects of the disease,” said co-author Sher Hendrickson.

The U5a1 and J haplogroups seem to be responsible for this lack of energy.

Hendrickson said that this means mitochondrial DNA tests could one day give an accurate prognosis for people with HIV, although further work on other genetic and environmental influence factors would be necessary first. (ANI)


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Offline John2038

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Re: John2038's Research News
« Reply #206 on: December 12, 2008, 01:51:51 AM »
RNA Interference Can Facilitate Vaccine Development

Pharmaceutical companies and universities are racing to develop drugs that use the gene silencing mechanism known as RNA interference to treat a host of diseases. Now, a new study opens up an entirely new possibility for this powerful tool: Researchers at the University of Georgia have demonstrated for the first time that RNA interference can be used as a tool in the development of vaccines.

"Our data suggest that, at least in an animal model system, an RNAi prophylactic treatment can reduce infection and disease pathogenesis while also acting like a vaccine to engender immunity that protects against subsequent re-infection," said Ralph Tripp, Georgia Research Alliance Eminent Scholar in Vaccine Development at the UGA College of Veterinary Medicine.

Tripp, whose results appear in the December issue of the Journal of Virology, co-authored the study with doctoral student Wenliang Zhang. Previous studies by Tripp and other researchers have shown that treating mice with a small interfering RNA (siRNA) drug can reduce the replication of respiratory syncytial virus and reduce the duration of illness. RSV is a common virus that causes flu-like symptoms in otherwise healthy adults but can be fatal in infants, the elderly and people with compromised immune systems. Work from the Tripp lab has already contributed to the testing of an RNAi therapeutic for RSV infection known as ALN-RSV01, which is undergoing phase II clinical trials initiated by Cambridge, Mass.-based Alnylam Pharmaceuticals, Inc. In the latest study, Tripp explored how a related drug impacts the body's ability to respond to later infection.

The researchers treated mice with the siRNA drug, and, for control groups, treated mice with a non-specific siRNA or saline. In prophylactic treatments in which the mice were given the drug 12 hours before RSV infection, the siRNA drug reduced the viral load by up to 80 percent compared to both controls. The drug also prevented detectable disease in the mice.

Tripp pointed out that RSV replication was reduced in a dose-dependent manner, meaning that the viral load decreased in proportion to the amount of drug administered. He said it's possible to halt viral replication entirely with higher doses of the drug, but that his goal was to expose the immune system to enough of the virus so that it could mount a strong response upon future exposure.

In the next phase of the study, the researchers took mice that three weeks earlier were exposed to RSV after being prophylactically treated with either the drug or the controls and challenged them with the virus for a second time. The researchers found that levels of specific cells associated with the memory immune response were substantially increased in the experimental group versus the control groups, while the mice treated with the siRNA drug had virus concentrations that were more than 80 percent less than the control groups and recovered an average of two days faster.

"This is the first study of its kind to show the utility of using any siRNA to improve the immune system's memory response to an infectious agent," Tripp said. "We were able to reduce virus replication enough to prevent the development of disease but still induce immunity later on."

Between 75,000 to 125,000 children under age one are hospitalized with complications of RSV annually, according to the Centers for Disease Control and Prevention. Tripp notes that there is currently no effective vaccine for the virus. Unlike most viruses, the exact same strain of RSV can infect the same person repeatedly. Scientists are just now beginning to understand the many ways in which RSV evades the memory immune response, but Tripp's finding reveals that keeping RSV replication and protein expression at a low level prevents the virus from eluding the immune system.

Tripp said preliminary data also suggest siRNA drugs are likely to behave as effective vaccines for other common viral diseases, such as influenza and measles, and may help control outbreaks of emerging infectious diseases.

"Making siRNAs today is relatively simple because most disease-causing viruses have been sequenced or have closely-related cousins with conserved regions in their genes that can be targeted," Tripp said. "So you could prophylactically treat an animal, challenge it with the virus and see if you get reduced replication of the virus and whether that is sufficient to vaccinate against future challenge. Our data suggest that this is going to be a good strategy."

The research was supported by the Georgia Research Alliance



Source

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HIV DART 2008
Rio Grande, Puerto Rico
December 9-12, 2008


Dropout Rate in Study of US Minority Women Near 25% at 24 Weeks

Almost one quarter of antiretroviral-experienced women enrolled in the GRACE trial of darunavir/ritonavir dropped out of the study by week 24, but usually not because of side effects and in only one case because of virologic failure. GRACE (Gender, Race, and Clinical Experience) aimed to enroll minority women in the United States and Puerto Rico and succeeded in recruiting a population that is nearly two thirds African American and nearly one quarter Hispanic. The dropout rate suggests the difficulties in treating a poor, often marginalized population, even in a wealthy country. (from Jules: and the diffiulty of completing a study in the patient population, particularly when there are so many more treatment options available today as compared to years ago without having to remain in a study).

...

Siliciano Proposes Novel Gauge of Antiretroviral Activity

A new way to rate antiretroviral activity ranks darunavir as the strongest current antiretroviral. Tied for second place are saquinavir and indinavir.
What's wrong with this picture? Nothing, according to Robert Siliciano of Johns Hopkins University. The first scientist to show that current antiretroviral combinations cannot eradicate the virus, Siliciano seems set to shake up the HIV field again with a new yardstick--instantaneous inhibitory potential (IIP)--to gauge activity of antiretrovirals.
Everyone would agree that darunavir, the highest-ranking drug in Siliciano's scheme, is a powerhouse antiretroviral. But saquinavir and indinavir? And the surprises don't end there. Integrase inhibitors like raltegravir are no stronger than nucleosides, according to IIP analysis. Nonnucleosides (NNRTIs) do a little better.
Siliciano spelled out the details at HIV DART 2008 [1] and in a recent Nature Medicine report. He argued that standard dose-response methods, like 50% inhibitory concentration (IC50) or inhibitory quotient (drug concentration/IC50), have a severe limit: They're linear, while potent antiretroviral combinations have an exponential (logarithmic) impact in limiting viral replication. As a result, Siliciano proposed, you need a logarithmic scale to measure antiretroviral activity.

Hint of Higher Foot-Fracture Risk With Tenofovir-Containing Regimens

A retrospective case series from the Cedars-Sinai Health System in Los Angeles suggested a slightly higher risk of foot fracture among men taking tenofovir than among those not taking this antiretroviral [1]. Earlier research tied tenofovir to lower bone mineral density in adults and children [2-4]. But a bone substudy of the SMART treatment interruption trial did not isolate tenofovir as a risk factor for decreasing bone density [5]. In the Cedars-Sinai analysis, an array of contributing factors makes it impossible to discern the impact of tenofovir on foot fractures in these patients.
Collaborating with investigators from GlaxoSmithKline (the maker of competing products), the Cedars-Sinai team scrutinized medical records of all HIV-infected men in the Cedars-Sinai system with MRI-confirmed foot fractures. Among the 30 men with broken foot bones, 17 (57%) had taken a tenofovir-containing regimen before the fracture and 13 (43%) had not. Median time from starting tenofovir to foot fracture measured 2.57 years and ranged from 1.17 to 5.69 years.

...

Early Results With Antiretrovirals Plus Immunotoxins That Target Viral Reservoirs

Immunotoxins that target resting HIV-infected cells could prove a valuable adjunct to antiretroviral therapy, according to Edward Berger of the National Institute of Allergy and Infectious Diseases, who discovered the CXCR4 coreceptor on CD4 cells [1]. Several years of immunotoxin research show that combining these agents with antiretrovirals prevents viral rebound after antiretroviral treatment stops in a mouse model of HIV infection. Immunotoxins alone kill cells chronically infected with HIV while largely sparing uninfected cells.
Berger outlined results on two immunotoxins. CD-PE40 is a recombinant single-chain chimeric protein containing the translocation and cytotoxic domains of Pseudomonas aeruginosa exotoxin A linked to a specific protein that binds to HIV-1 Env. This immunotoxin targets Env with soluble CD4. 3B3-PE38 is a similar construct, but it homes in on Env with a single-chain antibody fragment (scFv) of the 3B3 monoclonal antibody.
CD4-PE40 killed chronically HIV-infected cells at a 50% inhibitory concentration (IC50) of approximately 2 nM. 3B3-PE38 killed the cells much more efficiently, at an IC50 of 0.03 nM. Both immunotoxins limited viral spread in peripheral blood mononuclear cells in experiments using HIV-1 isolates of various strains, with 3B3-PE38 again flexing more antiviral muscle [2]. 3B3-PE38 also blocked spreading infection in primary macrophages. The immunotoxins had negligible activity against cells not infected by HIV.

...



-----------

Panacos Provides Update on Corporate Strategy

The Company is reducing its workforce, effective immediately, from 33 employees to 15. These actions are being taken to manage capital resources while Panacos pursues strategic alternatives, including the financing, partnering or sale of the Company or one of its several antiviral assets, including bevirimat (PA-457), the Company's first-in-class maturation inhibitor, which is currently in Phase 2b clinical studies in HIV-positive patients, the next-generation maturation inhibitor program (consisting of second- and third-generation compounds) and the oral fusion program (consisting of its lead compound, PA-161).

"Our talented and dedicated development team has worked so diligently on programs that continue to show great promise," stated Alan W. Dunton, MD, President and Chief Executive of Panacos. "However, we are faced with the reality that we must take drastic measures to reflect the current market environment. These actions are in line with our goal to secure partnerships or sale for our spectrum of HIV programs, including bevirimat, our second- and third-generation maturation inhibitors, as well as the oral fusion inhibitor program. Ultimately, everyone at Panacos is dedicated to ensuring HIV patients have access to these compounds, as there are limited choices for patients once their virus becomes resistant to the treatments that are currently available."

As of September 30, 2008, unrestricted cash, cash equivalents and marketable securities totaled $26.9 million. Under the terms of the recently terminated loan agreement with Hercules Technology Growth Capital, Inc. (NASDAQ: HTGC), Panacos paid Hercules approximately $17.9 million on Monday, November 24, 2008. As of December 8, 2008, unrestricted cash, cash equivalents and marketable securities totaled approximately $4.7 million. The Company is seeking additional sources of capital to continue operations.

Panacos' Development Programs

Panacos' lead compound, bevirimat (PA-457), is the first in the new class of HIV drugs under development called maturation inhibitors, discovered by Company scientists and their academic collaborators. Bevirimat is designed to have potent activity against a broad range of HIV strains, and studies have shown bevirimat is a potent inhibitor of HIV isolates that are resistant to currently approved drugs. Panacos has completed 15 clinical studies with bevirimat in nearly 650 patients and healthy volunteers, showing significant reductions in viral load in HIV-infected patients and a promising safety profile. It is currently in Phase 2b clinical studies. The Company previously determined the optimal dose range of bevirimat and identified patient response predictors to bevirimat, which now have been confirmed in multiple laboratory analyses and a prospective study. Panacos has recently developed a tablet formulation of bevirimat that demonstrates bioavailability and pharmacokinetics comparable to that of the previous solution formulation (Study 114). The Company has also completed a Phase 2b study of bevirimat (Study 204) that confirmed an optimal dose can be achieved with a twice daily dose of bevirimat tablets. Efficacy and additional safety data obtained from Study 204 support the Company's view that the 100mg bevirimat tablet formulation should be studied further in HIV patients.

In addition to bevirimat, the Company has second- and third-generation programs in HIV maturation inhibition that include compounds with activity against HIV containing Gag polymorphisms. Panacos has also selected a lead compound, PA-161, for preclinical development in its oral HIV fusion inhibitor program.



Source

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Increasing number of HIV/AIDS cases recorded in Philippines, official says

The registry shows that 59 new HIV cases were recorded in October, with 19% of the cases involving young people ages 15 to 24 and 27% involving people ages 25 to 29.

The Philippine's Department of Health has recorded an 84% increase in the number of HIV/AIDS cases since it began monitoring in 1984, causing some officials to express concerns about the increasing prevalence of the disease in the country, the Manila Bulletin reports. Joel Atienza -- technical component manager at the health department for a Global Fund To Fight AIDS, Tuberculosis and Malaria Round 6 HIV/AIDS Project -- said that the number of cases recorded by the National AIDS Registry from January to October of this year is "alarming" because the "number is double than last year's increase." He added that it is "already near 100%."

According to the Bulletin, the registry shows that 59 new HIV cases were recorded in October, with 19% of the cases involving young people ages 15 to 24 and 27% involving people ages 25 to 29. Atienza said that most of the youth cases involved boys and men and that the "sudden increase" of new cases seen in October leads him to "[think] that the youth are really engaging in early sexual debut." However, he added that the increase could be "attributed to the youth's awareness on the services of the [health department] and they are accessing these health services." According to the Bulletin, about 12% of the total number of cases in last year's national registry involved young people. According to the Bulletin, 13 of the 59 cases affected men and all newly reported cases were transmitted sexually (Manongdo, Manila Bulletin, 12/10).


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Offline John2038

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« Reply #207 on: December 13, 2008, 10:17:57 AM »
DART

Darunavir vs Lopinavir at 96 Weeks in People With Naïve Advanced HIV - ARTEMIS Study

Antiretroviral-naive people starting treatment with once-daily darunavir/ritonavir had a significantly better 96-week virologic response than those starting once- or twice-daily lopinavir/ritonavir in the ARTEMIS trial. Response differences between darunavir and lopinavir were more marked among people who began treatment with a viral load above 100,000 copies or a CD4 count under 200. The findings extend recently published 48-week results.


Raltegravir Efficacy and Safety After 96 Weeks of Phase 2 Trial
 
Nearly half of heavily pretreated people who took the integrase inhibitor raltegravir for 96 weeks in the phase 2 protocol 005 had a viral load below 50 copies in a noncompleter-equals-failure analysis [1]. Nine of 94 people (9.6%) who continued raltegravir in the trial's open-label phase had a virologic rebound above 50 copies after week 48.


AIDSMAP


Adherence of 80-95% not good enough for long-term treatment success in British Columbia HIV patients

Adherence of less than 95% is associated with a substantially lower chance of a good response to treatment, even using relatively relaxed definitions of virologic and immune success, according to a new analysis reported in AIDS. The study, by investigators in British Columbia, also found that people who took less than 80% of their medication (people likely to be missing doses on a weekly basis) had only a 10 – 15% probability of achieving and maintaining a good response to treatment during the four-year follow-up period, while those taking between 80% and 95% of all doses had no more than a 41% probability of a good response to treatment.


MISC

Advanced liver disease in people with HIV

As HIV positive people live longer due to effective antiretroviral therapy, liver disease has become an increasingly important cause of illness and death in this population.


Merck announces FDA acceptance of supplemental new drug application for ISENTRESS in adult patients previously untreated for HIV-1

ISENTRESS is approved for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.


Strange prosecution may result in case of HIV status forgery

A man who sought to have unprotected sex with a woman allegedly gave her a forged medical document stating he had tested negative for HIV. The man, who apparently knew he was HIV positive, now might face prison time.


Schering-Plough announces FDA approval of PEGINTRON and REBETOL combination therapy for treating pediatric hepatitis C

First and only approved peginterferon in combination with ribavirin for previously untreated children with chronic hepatitis C addresses unmet medical need.


Report examines discrimination against, social exclusion of HIV-positive people in Eastern Europe, CIS region

The report examined exclusion in the health, education and employment fields from the perspectives of people living with HIV.


Pope discusses HIV, TB, malaria in annual peace address

The pope called for education for young people and increased access to treatment for HIV/AIDS, TB and malaria for low-income people.

Offline John2038

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« Reply #208 on: December 19, 2008, 03:15:10 PM »
Critical new way a man can transmit the HIV virus to a woman discovered

Instead of infiltrating breaks in the skin, HIV appears to attack normal, healthy genital tissue, U.S. researchers said on Tuesday in a study that offers new insight into how the AIDS virus spreads.

Scientists had long believed that the normal lining of the female vaginal tract was an effective barrier to invasion of the HIV virus during sexual intercourse. They thought the large HIV virus couldn't penetrate the tissue.

But new research from Northwestern University's Feinberg School of Medicine has shown for the first time that the HIV virus does indeed penetrate a woman's normal, healthy genital tissue to a depth were it can gain access to its immune cell targets.

"This is an unexpected and important result," said Thomas Hope, principle investigator and professor of cell and molecular biology at the Feinberg School. "We have a new understanding of how HIV can invade the female vaginal tract."

"Until now, science has really had no idea about the details of how sexual transmission of HIV actually works," Hope added. "The mechanism was all very murky."

Full article


AIDS Nobel Laureate Joins Viral Genetics

Luc Montagnier, co-winner of the 2008 Nobel Prize for Medicine and the co-discoverer of the HIV virus, has joined Viral Genetics (OTCBB: VRAL), a biotechnology company that discovers and develops immune-based therapies.

Montagnier joins a current team of esteemed advisors with diverse expertise to help guide Viral Genetics as it develops unique therapies for HIV and other diseases of the immune system.

Dr. Montagnier, Nobel Prize winner 2008 for his role in the discovery of HIV, said:

“While some preventive candidate vaccines failed to protect against HIV infection, and since there is no treatment able to cure the disease, it is important to come back to basic research and to explore new ways of research and treatment such as those explored by Viral Genetics. This is why I joined the Advisory Board of this Company.”

The purpose of the Viral Genetics Advisors is to provide independent wisdom and insight to assist Viral Genetics in the accomplishment of its medical and scientific objectives by providing advice that is consistent with best-in-class scientific and medical practices and principles. Based on new information from ongoing AIDS and Lyme disease studies being led by head of research Dr. M. Karen Newell, PhD, new components of the mechanism of TNP, the Company’s drug compound, have been identified. Viral Genetics continues to aggressively seek out the appropriate individuals in relevant fields to assist as the studies continue to move forward. These will include highly sought-after individuals in many diverse fields of research. The existing group and new advisors to be added have come together in an effort to spearhead Viral Genetics’ promising new model of targeted peptide therapies for AIDS and other immune disease as swiftly as possible.

Dr. M. Karen Newell, head of Viral Genetics’ latest research and discoverer of TNP’s mechanism stated, "We are looking forward to the guidance of Dr. Montagnier in our efforts. He will not only help us in our research efforts, but also to identify experts in the studies of immune response genes and HIV, protein and peptide chemistry, cell death and apoptosis, pharmaco-genomics and computational biology. We look to augment our existing scientific advisory team with expertises that will strengthen and accelerate our ability to return to clinical trials - armed with a new and improved model, a newly identified potential mechanism of action, and a biologic product with characteristics of a novel, therapeutic vaccine strategy than has ever been tried in the past."

Full article


HIV transmission rate in US has declined enormously

Fewer people with HIV transmitted the infection to others in 2006 than ever before, according to new figures released by US researchers and published in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

Investigators from Johns Hopkins University and the US Centers for Disease Control and Prevention calculated that in 2006 95% of people with HIV did not pass on the infection to someone who was HIV-negative. They further calculated that there has been a steady decline in the rate of HIV transmission since the 1980s. They attribute this to the success of HIV prevention initiatives, particularly increased HIV testing.

The investigators calculated the rate of HIV transmission as the number of people with HIV per 100 who infected an HIV-negative individual in a year. Recent revisions in the HIV incidence rate in the US prompted the researchers to look at the rate of HIV transmission between 1977 and 2006.

Full article


Oral sex risk very low, but not zero, concludes systematic review

The risk of HIV transmission during oral sex is very low, but not zero, conclude researchers from Imperial College and the London School of Hygiene and Tropical Medicine in the December 2008 issue of the International Journal of Epidemiology. The researchers attempted to identify all the relevant observational studies on the topic, but found that given the lack of data, it would be inappropriate to make summary estimates for the transmission risk through oral sex.

The authors conducted a systematic review (an analysis of all the medical research on a particular subject that meets pre-defined requirements). Cohort studies and other observational studies were included, while case reports and reviews were excluded.

The studies reviewed include data from heterosexual, lesbian and gay couples, covering both fellatio and cunnilingus.

Full article

Offline John2038

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« Reply #209 on: December 20, 2008, 01:58:32 PM »

Natural Immune Response to HIV Not Sufficient to Prevent Secondary Superinfection

Researchers studying the phenomenon known as HIV superinfection have determined that the immune system's initial antibody response may not be sufficient to provide protection against later infection with a different HIV virus, a finding that may have significant implications for HIV vaccine development.

full story

Synthetic Molecules Prevent HIV Virus From Reproducing Within The Body, Study Suggests

Evolving HIV viral strains and the adverse side effects associated with long-term exposure to current treatments propel scientists to continue exploring alternative HIV treatments. In a new study, a University of Missouri researcher has identified broad-spectrum aptamers. Aptamers are synthetic molecules that prevent the HIV virus from reproducing. In lab tests, aptamers known as RT5, RT6, RT47 and some variants of those were recently identified to be broad-spectrum, which would allow them to treat many subtypes of HIV-1.

full story

Charting HIV's Rapidly Changing Journey In The Body

HIV is so deadly largely because it evolves so rapidly. With a single virus as the origin of an infection, most patients will quickly come to harbor thousands of different versions of HIV, all a little bit different and all competing with one another to most efficiently infect that person's cells. Its rapid and unique evolution in every patient is what allows HIV to evade the body's defenses and gives the virus great skill at developing resistance to a pantheon of antiviral drugs.

full story

New Therapy For Hepatitis C Treatment

Combination therapies similar to those used for HIV patients may be the best way of treating hepatitis C virus (HCV), say researchers from the University of Leeds.
A study of a protein called p7, has revealed that differences in the genetic coding of the protein between virus strains - known as genotypes - alter the sensitivity of the virus to drugs that block its function.

full story


Researchers Successfully Used the 454 Sequencing System for Sensitive Detection of HIV Tropism

Life Sciences, a Roche company, announced today that a team of researchers from the BC Centre of Excellence in HIV/AIDS and the University of British Columbia, Canada have used the Genome Sequencer FLX system to monitor low frequency HIV variants from human samples in a recent study. The preliminarily results of the study were presented by Dr. Richard Harrigan, the Centre’s Director of Research Labs at the HIV DART 2008 conference in Puerto Rico in a presentation entitled “Quantification of HIV Tropism by Deep Sequencing Shows a Broad Distribution of X4 Variants in Clinical Samples Associated with Virological Outcome.”

The background of this research study is that correct determination of “HIV tropism” is critical for the administration of a new class of drugs called CCR5 antagonists used for the treatment of AIDS. HIV tropism refers to the type of cell the HIV virus infects, as determined by so-called co-receptors that the virus employs for entry into the cell. Determining the co-receptor that a HIV strain uses, either CCR5, CXCR4 or a combination of both, is a critical component of monitoring and treating HIV.

full story

Hospital admits a mistake when it told a man he has HIV

Video


HIV couples will be allowed to marry

KUALA LUMPUR: All Muslim couples in the peninsula will have to undergo mandatory screening for the human immunodeficiency virus (HIV) before they get married.

full story

Malaysia to impose mandatory pre-marital HIV/AIDS screening

Kuala Lumpur - Couples in Malaysia will be required to undergo mandatory screening for HIV infection before they can get married, a news report said Thursday.

full story

Offline John2038

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« Reply #210 on: January 10, 2009, 11:08:27 AM »
Interactions Between Drugs for Erectile Dysfunction and Other Medications

Anyone with a television probably knows that three prescription medications currently are used to treat erectile dysfunction (ED):

- sildenafil (VIAGRA)
- tadalafil (CIALIS)
- vardenafil (LEVITRA).

These drugs, which belong to the class of drugs called phosphodiesterase-5 inhibitors (PDE5i), are widely used, especially in older men. And because older men are more likely to be concurrently taking other medications, they should be aware of the potential for dangerous interactions when ED drugs are mixed with other prescription drugs. This article deals only with these three approved prescription ED drugs, not the many untested ED products widely advertised on the Internet and elsewhere (see Tables 1, 2, and 3).

How do ED drugs interact?
Sildenafil, tadalafil and vardenafil are drugs that cause the dilation of blood vessels (vasodilators) and this effect can be magnified when they are used with other medications with similar vasodilating effects. It is this vasodilating effect that increases blood flow to the penis causing an erection. Most ED drug interactions, however, result from the fact that these drugs are metabolized by the enzyme CYP3A4 in the intestine and liver. CYP3A4 is the most important enzyme for drug metabolism, and many medications can interact with ED drugs by decreasing or increasing CYP3A4 activity, causing ED drug levels to increase or decrease, respectively.

Interactions with vasodilators

People who take nitrates (drugs commonly used to dilate the blood vessels in the heart for patients with coronary artery disease, such as nitroglycerin), either on a regular schedule or as needed, should not use these ED drugs. A dangerous reduction in blood pressure may occur, potentially leading to a heart attack or stroke, and so these drugs should not be used in combination. ED drugs also can enhance the blood pressure-lowering effects of alpha blockers such as doxazosin (CARDURA), prazosin (MINIPRESS), terazosin (HYTRIN), tamsulosin (FLOMAX) and alfuzosin (UROXATRAL). These drugs are used to treat both high blood pressure and enlarge prostate glands. If you are on an alpha blocker, consult your physician before taking an ED drug; he or she may recommend dosage adjustments or other precautions.

Interactions with drugs that decrease CYP3A4 activity
Drugs that inhibit CYP3A4 can substantially increase plasma concentrations of ED drugs, potentially leading to toxicity. See Table 2 for a list of drugs that inhibit CYP3A4. If you are taking any of these drugs, check with your physician before taking an ED drug. Your physician may advise a dosage reduction of the ED drug, especially if you are taking a potent CYP3A4 inhibitor such as ketoconazole, itraconazole or ritonavir. Keep in mind that grapefruit juice is also a CYP3A4 inhibitor.

Interactions with drugs that increase CYP3A4 activity
Drugs that increase CYP3A4 activity (see Table 3) tend to reduce the effect of ED drugs. This is not dangerous, of course, but it may render the ED drug ineffective. If the increased CYP3A4 activity is marked — such as in patients taking the antibiotic rifampin, even the highest recommended dose of the ED drug may be ineffective. Again, if you are taking any of the medications in Table 3, talk to your physician before starting an ED drug so he or she will know that the effect of the ED drug may be compromised. (See Tables 1, 2 and 3 on Page 3.)

What You Can Do
Many medications have the potential to interact with ED drugs, so it is important to make sure that the physician prescribing the ED drug is aware of all the other medications you are taking. If you start or stop other medications after receiving a prescription for an ED drug, check to make sure your ED drug effect will not increase or decrease as a result.


Table 1: List of Drugs That May Cause Excessive Decreases in Blood Pressure When Taken with ED Drugs

Nitrates
Generic NameBrand Name
Isosorbide dinitrateDILATRATE-SR, ISORDIL, SORBITRATE
Isosorbide mononitrateIMDUR, ISMO, MONOKET
NitroglycerinMINITRAN, NITRO-BID, NITRO-DUR, NITROSTAT, TRANSDERM-NITRO

Alpha Blockers
Generic NameBrand Name
Doxazosin**CARDURA**
Prazosin*MINIPRESS*
Terazosin*HYTRIN*
Tamsulosin**FLOMAX**
Alfuzosin***UROXATRAL***


Table 2. Drugs That May Cause ED Drug Toxicity by Decreasing CYP3A4 Activity
Generic NameBrand Name
AmprenavirAGENERASE
AprepitantEMEND
AtazanavirREYATAZ
Clarithromycin**BIAXIN**
ConivaptanVAPRISOL
CyclosporineNEORAL, SANDIMMUNE
DarunavirPREZISTA
DasatinibSPRYCEL
DelavirdineRESCRIPTOR
Diltiazem**CARDIZEM, CARDIZEM CD, DILACOR XR, TIAZAC**
ErythromycinEES, ERYTHROCIN
FluconazoleDIFLUCAN
Fluvoxamine**LUVOX**
FosamprenavirLEXIVA
Grapefruit Juice-
ImatinibGLEEVEC
IndinavirCRIXIVAN
Itraconazole*SPORANOX*
KetoconazoleNIZORAL
LapatinibTYKERB
MifeprestoneMIFEPREX
Nefazodone*SERZONE*
NelfinavirVIRACEPT
PosaconazoleNOXAFIL
QuinupristinSYNERCID
RitonavirNORVIR
SaquinavirFORTOVASE, INVIRASE
Telithromycin*KETEK*
TroleandomycinTAO
VerapamilCALAN, CALAN SR, COVERA-HS, ISOPTIN, ISOPTIN SR, VERELAN
VoriconazoleVFEND
Zafirlukast*ACCOLATE*


Table 3. Drugs That May Inhibit the Effect of ED Drugs by Increasing CYP3A4 Activity
Generic NameBrand Name
AminoglutethimideCYTADREN
BosentanTRACLEER
CarbamazepineCARBATROL, TEGRETOL
DexamethasoneDECADRON, HEXADROL, MYMETHASONE
EfavirenzSUSTIVA
Modafinil*PROVIGIL*
NafcillinNALLPEN, UNIPEN
NevirapineVIRAMUNE
OxcarbazepineTRILEPTAL
Phenobarbital**LUMINAL, SOLFOTON**
PrimidoneMYSOLINE
PhenytoinDILANTIN
RifabutinMYCOBUTIN
RifampinRIFADIN, RIMACTANE
RifapentinePRIFTIN
St. John’s wort-

* Do Not Use in Worst Pills, Best Pills News
** Limited Use in Worst Pills, Best Pills News
*** Do Not Use Until 2010 in Worst Pills, Best Pills News

Source
« Last Edit: January 10, 2009, 11:10:43 AM by John2038 »

Offline John2038

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« Reply #211 on: January 10, 2009, 11:22:45 AM »
NATAP News

Prospective study of physical fitness, adiposity, and inflammatory markers in healthy middle-aged men and women
In summary, changes in low-grade inflammation were positively associated with adiposity but not with fitness. Fit-overweight participants do, however, appear to have a lower risk of CVD than do their unfit counterparts. Because the excess risk of CVD events associated with obesity is partly explained by inflammation-sensitive plasma proteins, the antiinflammatory effects of exercise may partly contribute to a lower CVD risk in obesity.....

ICAAC: New CCR5 Drug PRO 140 Reduced Viral Load by 2 Logs With Single 10 mg Intravenous Dose;
5/5 patients with single 10 mg dose had >2 log reduction in viral load








Childhood Trauma and Neurological Development and Stress, and Chronic Fatigue Syndrome

We previously suggested that early adverse experience such as childhood abuse, neglect, and loss might be a predisposing factor that interferes with successful adaptation to stress, thereby conveying risk to develop CFS.7 This hypothesis was based on evidence from developmental neurosciences suggesting that stress early in life within a genetic window of vulnerability permanently programs the organism's responsiveness to subsequent stress throughout the lifespan. These long-term consequences of early-life stress occur through direct effects on brain circuits implicated in the mediation of cognitive-emotional regulation, vigilance, arousal, and the integration of endocrine, autonomic, and immune regulatory systems.8-10 Of note, similar changes in these circuits and regulatory outflow systems have been implicated in the pathophysiology of CFS.11-12 It is therefore conceivable that adverse experience in childhood is causally associated with developing CFS, particularly in response to challenge.

AIDS Denialism by South African Govt Leader Pres Mbeki Loses 330,000 Lives & 35,000 HIV+ Babies Born
More than 330,000 lives or approximately 2.2 million person-years were lost because a feasible and timely ARV treatment program was not implemented in South Africa. Thirty-five thousand babies were born with HIV, resulting in 1.6 million person-years lost by not implementing a mother-to-child transmission prophylaxis program using nevirapine. The total lost benefits of ARVs are at least 3.8 million person-years for the period 2000-2005.

The incidence of and risk factors for MRSA bacteraemia in an HIV-infected cohort in the HAART era
To the best of our knowledge, this is the largest study of S. aureus bacteraemia to date in a US HIV-infected population. This study has several important findings. First, MRSA represented a large and growing proportion of S. aureus bacteraemias among our urban cohort of HIV-infected patients. Secondly, patients with MRSA bacteraemia were more likely to have low CD4 cell count, IDU exposure, and ESRD than were bacteraemia-free controls. Compared with patients with MSSA bacteraemia, those with MRSA bacteraemia were more likely to have ESRD and showed a trend towards a greater level of immunocompromise as measured by CD4 cell count."...."Initial antimicrobial therapy for presumed sepsis in HIV-infected patients may require agents active against MRSA, including vancomycin, linezolid and, in nonpulmonary infections, daptomycin, particularly in patients with risk factors for MRSA bacteraemia.

Long-term consequences of the delay between virologic failure of HAART and regimen modification
Among patients with a first HAART failure on a reverse transcriptase inhibitor-based regimen, a 3-month delay until treatment modification was associated with an elevated hazard of mortality and immunologic failure (hazard ratio = 1.23; 95% confidence interval (CI) 1.08, 1.40; P = 0.002 for death and hazard ratio = 1.21; 95% CI 1.07, 1.36; P = 0.002 for immunologic failure) (Table 3). In comparison, among patients failing a protease inhibitor-based first HAART regimen, a 3-month delay until treatment modification slightly reduced the hazard of mortality (hazard ratio = 0.93; 95% CI 0.87, 0.99; P = 0.03 for death and hazard ratio = 0.98; 95% CI 0.94, 1.03; P = 0.45 for immunologic failure); however, this weak association should be interpreted cautiously given the multiple comparisons performed. These findings were reasonably consistent across cohorts and following second HAART failures

Minority Quasispecies of Drug-Resistant HIV-1 That Lead to Early Therapy Failure in Treatment-Naive and -Adherent Patients
By using AS-PCR (sensitive genotypic test) , we were able to show a rapid outgrow of minority quasispecies of drug-resistant viruses, undetected at baseline by conventional genotyping, that led to eVF despite excellent adherence and a potent standard regimen of lamivudine, tenofovir, and either efavirenz or nevirapine. Further studies to confirm the clinical benefit of the detection of minority quasispecies of drug-resistant viruses before starting ART in treatment-naive patients are warranted, especially in the context of ART regimens with low genetic barriers to resistance.

The Management of Treatment-Experienced HIV-Infected Patients: New Drugs and Drug Combinations
Recent availability of new antiretroviral agents for HIV treatment....has led to a revision of current treatment guidelines, which now state that the goal of antiretroviral therapy in all patients is suppression of the plasma HIV RNA level to <50 copies/mL.....it is critical that clinicians use the new agents carefully and that patients understand the importance of adherence. The DUET [4, 5], MOTIVATE [20], and BENCHMRK [12-14] studies suggest that an effective and durable regimen should include at least 2-and preferably 3-active agents. The years 2007 and 2008 will be viewed as a landmark in this history of HIV therapy, because for the first time, almost all patients with access to therapy can now achieve virological suppression. Whether this is the beginning of a new era or just a brief "honeymoon period" will depend on how we use these valuable new agents

Switching from suppressive protease inhibitor-based regimens to nevirapine-based regimens: a meta-analysis of randomized controlled trials
...In our meta-analysis we observed that replacement of a PI by NVP had similar efficacy as continuation of PI-based therapy to maintain virological suppression. By intention-to-treat analysis, 81.2% of patients in the NVP group maintained viral suppression at the end of follow-up compared with 77.7% in the PI group. By on-treatment analysis, the figures were 91.1 and 88.5%, respectively. The efficacy of this strategy was similar to that reported for EFV substitution of PI-based therapy....
...The rate of hepatotoxicity leading to NVP discontinuation ranged in the literature from 12.5 to 21% in ARV-naive patients [32-34]. In most studies the risk was greater among persons with chronic viral hepatitis [32-33]. However, the risk of NVP discontinuation was lower in antiretroviral therapy-experienced patients than in ARV-naive patients in the EuroSIDA cohort, even in those with high CD4 cell counts [35]. A study conducted in India using generic NVP-based therapy in ARV-experienced men and women with elevated CD4 cell counts found no cases of severe hepatotoxicity [36]. It should be emphasized that patients on PIs were tolerating these drugs reasonably well, while the introduction of NVP runs the unavoidable risk of toxicity associated with this drug. Nevertheless, our meta-analysis showed no differences in the overall withdrawal rate between the two arms....

Lipoatrophy among HIV-infected patients is associated with higher levels of depression than lipohypertrophy

In this study of 250 HIV-infected patients attending the clinic for routine visits we found a high prevalence of body morphology abnormalities: 82% of patients had at least some degree of lipoatrophy or lipohypertrophy. Most abnormalities were mild, with 13% of patients reporting moderate-to-severe lipoatrophy or lipohypertrophy. Mean depression scores were significantly higher among patients with lipoatrophy or lipohypertrophy.....

Annual Zoledronate Increases Bone Density in Highly Active Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Men: A Randomized Controlled Trial
"MANY cross-sectional studies have reported low bone mineral density (BMD) or higher than expected rates of osteopenia and osteoporosis in people infected with HIV"
"Participants received annual iv administration of 4 mg zoledronate or placebo. All participants took 400 mg/d calcium and 1.25 mg/month vitamin D. Zoledronate is a potent third-generation bisphosphonate."
"At the lumbar spine, BMD increased by 8.9% over 2 yr in the zoledronate group compared with an increase of 2.6% in the control group (P < 0.001). At the total hip, BMD increased by 3.8% over 2 yr in the zoledronate group compared with a decrease of 0.8% in the control group (P < 0.001). At the total body, BMD increased by 2.3% over 2 yr compared with a decrease of 0.5% in the control group (P < 0.001)."
"The current study provides evidence for the efficacy of zoledronate in the treatment of HIV-infected men who manifest significant bone loss. We found that zoledronate significantly increased BMD at the lumbar spine, hip, and total body in HIV-infected men treated with HAART, and that the between-group differences in BMD at all sites tended to increase throughout the study. Bone resorption decreased substantially by 3 months and remained stable thereafter. This is the first report of the effects on BMD of annual administration of the potent bisphosphonate, zoledronate, in men, in HIV-infected subjects, or with drug administration beyond 12 months."

Once A Year Zoledronate Bone Therapy Increased Bone Density & T-Scores
HIV-associated osteopenia and osteoporosis is common with reported prevalence rates of 51-67% in various cohorts [4,5] and can result in significant morbidity [6]. Simplified regimens for HIV-associated osteopenia and osteoporosis could help to ensure compliance to all medications, as they must be taken concurrently with antiretroviral therapy......we have confirmed that annual dosing of zoledronate treats osteopenia and osteoporosis in HIV-infected men. As in other populations, this therapy probably acts by reducing bone resorption as shown by biomarkers. Zoledronate was well tolerated by our study cohort except for one episode of uveitis. Its combination of good tolerability, low medication burden, and effectiveness make zoledronate an excellent candidate to treat a common complication of chronic therapy for a life-threatening disease.....At 12-months patients receiving zoledronate increased their bone density at the lumbar spine by 3.7 ± 4.1% (mean ± SD) compared with patients receiving placebo (0.7 ± 3.1%, P = 0.04). Likewise, bone density at the hip increased at 12 months by 3.2 ± 2.2% in zoledronate recipients compared with controls (-1.8 ± 9.3%) (P = 0.016). T-scores also significantly increased at both the lumbar spine and hip over the 12-month study period in the zoledronate group compared with placebo (Fig. 1a and b). Bone density improvements in the lumbar spine peaked at 6 months among zoledronate recipients, but continued to improve over 12 months at the hip.....

Thyroid Dysfunction & Bone Disease in HIV & HCV; Thyroid Testing Recommended by UK Group
« Last Edit: January 10, 2009, 11:27:32 AM by John2038 »

Offline John2038

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« Reply #212 on: January 15, 2009, 04:21:21 PM »
NATAP News

CDC Updates New HIV Cases Surveillance Estimates: "the disease continues to affect the MSM population more than any other in the United States"
The distribution of new HIV infections in 2006 demonstrates that, more than 25 years after the first report of AIDS, the disease continues to affect the MSM population more than any other in the United States.....the age distribution of persons with new infections suggests important differences by race and ethnicity. Among black and Hispanic MSM, most new infections were in persons aged 13-29, whereas, among white MSM, most new infections were in persons aged 30-39 years.....new infections of HIV occurred disproportionately among blacks and Hispanics.2 The results in this report indicate further that the disparity between racial/ethnic minorities and whites is greatest among females......comprehensive surveillance systems are essential for HIV incidence estimation. All states are now implementing confidential, name-based HIV surveillance, and national data on HIV diagnoses and incidence likely will continue to improve.....CDC supports state and local health departments and community-based organizations to promote effective HIV prevention interventions that target those persons at greatest risk for HIV infection.

C-Reactive Protein and Reclassification of Cardiovascular Risk in the Framingham Heart Study
Circulating levels of CRP help to estimate risk for initial cardiovascular events and may be used most effectively in persons at intermediate risk for vascular events, offering moderate improvement in reclassification of risk.

Researchers Identify IL-7 New Regulatory Circuit Controlling Immune Cell Production in Mice
To investigate the role of IL-7 in CD4+ T cell homeostasis, the researchers injected T cells labeled with a marker into mice depleted of lymphocytes, and, in a subset of these mice, they also administered laboratory-produced IL-7 to further increase the level of IL-7 in the blood. Using flow cytometry, a laboratory technique that allows researchers to measure the concentrations of different types of cells, they found that, within seven days, most of the CD8+ T cells had divided, but the proliferation of CD4+ T cells was minimal.
Dendritic cells are a specialized type of white blood cells that can potently induce T cell activation, and some of these cells contain cell surface proteins that act as receptors for IL-7. Mackall's team also found that interruption of IL-7-induced signaling in these dendritic cells led to an increase in CD4+ T cell proliferation. Cell signaling is a biochemical pathway that regulates cellular functions, such as proliferation or survival. The researchers say that this finding identifies a new regulatory circuit that prevents uncontrolled CD4+ T cell proliferation in mice.

Prolonged Nevirapine Use In Breast-Fed Babies Prevents HIV, Increased Resistance Risk
Investigators analyzed samples from 74 Indian babies infected with HIV; 22 were infected before birth, 19 during birth or during early breast-feeding (three to six weeks after birth), and 33 during late breast-feeding (around six months after birth). Of the 19 infants infected through breast-feeding in the first six weeks of life, four were given daily nevirapine for six weeks, and 15 received a single dose at birth. All four babies on extended nevirapine developed resistant strains of the virus, while only four of the 15 given a single dose tested positive for resistant strains after infection.
 
Factors Associated with Acquisition and Clearance of Human Papillomavirus Infection in a Cohort of US Men: A Prospective Study
Lifetime number of sex partners reported at enrollment was the most significant risk factor for acquisition of all types of HPV. Men reporting >16 lifetime sex partners were at significantly elevated risk of any HPV infection (adjusted hazard ratio [AHR], 2.8 [95% confidence interval {CI}, 1.1-7.1]), oncogenic HPV infection (AHR, 9.6 [95% CI, 2.4-37.8]), and nononcogenic HPV infection (AHR, 3.6 [95% CI, 1.3-9.9]), compared with those reporting 0-4 partners. Circumcised men were 3 and 6 times more likely to clear infection with any and oncogenic HPV types, respectively. In addition, having had >16 lifetime sex partners was associated with greater likelihood of clearance of oncogenic HPV infection (AHR, 4.9 [95% CI, 1.2-19.8])

Our results suggest that HIV-1 infection induces an accelerated aging of T lymphocytes, which is associated with the clinical progression to AIDS and death
HIV-1 disease progression is associated with a decreased CD28 median florescence intensity on CD4+ and CD8+ T cells; an increased proportion of intermediate- and late-differentiated CD8+ T cells and a decreased CD31 median florescence intensity on naive CD4+ T cells of recent thymic origin. A selective depletion of peripherally expanded naive CD4+ T cells was found to be associated with HIV-1 infection but not with HIV-1 disease progression.
Conclusions:The overall change during HIV-1 infection and progression is associated with a shift in the T-cell population toward an aged conformation, which may be further compromised by impaired renewal of the less-differentiated CD4+ T-cell population. Our results suggest that HIV-1 infection induces an accelerated aging of T lymphocytes, which is associated with the clinical progression to AIDS and death.
 
Insulin Resistance (25%) Is Associated With Advanced Liver Fibrosis and High Body Mass Index in HIV/HCV-Coinfected Patients
Approximately a quarter of HIV/HCV-coinfected patients who underwent a liver biopsy to assess their suitability for anti-HCV therapy had IR. We also found that IR was associated with advanced liver fibrosis and a high BMI.

Cardiovascular Complications in HIV Management: Past, Present, and Future [Critical Review: Clinical Science]
Patients infected with HIV share traditional cardiovascular disease risk factors with the general population. In addition, HIV infection itself significantly increases the risk of cardiovascular disease. Control of viremia with potent and durable regimens can help reduce overall risk. Thus, effective suppression of viral replication and management of traditional risk factors (eg, lipids, blood pressure, smoking) with conventional methods provide the best approach to lowering total cardiovascular risk in patients with HIV infection. Although there is evidence that HAART may have negative effects on the serum lipid profile, these are modest, and the incremental cardiovascular risk associated with HAART is small and may be managed with treatments (eg, statins, fibrates, ezetimibe) commonly used in the general population. Switching antiretroviral agents may not resolve lipid abnormalities and should be cautiously considered, weighing the small but potential risk of virologic failure. A determination of the absolute risk of coronary heart disease in individual patients with the use of Framingham score calculations or other global risk calculators can provide valuable guidance for patient management and treatment planning.

Predictive Factors for Long-Term Non-Progressors
Background: To clarify early correlates and natural history of HIV long-term nonprogressors (LTNPs) since HIV diagnosis.
Methods: Patients enrolled in the French ANRS SEROCO/HEMOCO cohort with CD4 count >500 cells/mm3 at HIV diagnosis. LTNP status was defined as being asymptomatic, antiretroviral free, and with CD4 cell count >500 cells/mm3 for >8 years after HIV diagnosis. In LTNPs, we modeled the biological markers' progression through a joint model. Factors associated with loss of LTNP status were identified through a Cox model.
Results: Sixty (9%) of 664 patients were identified as LTNPs during follow-up. At enrollment, HIV RNA was ?2.6 log copies/mL in 24% of LTNPs and HIV DNA was ?1.85 log copies/106 peripheral blood mononuclear cells (PBMCs) in 31% vs. 3% and 8% in others. In LTNPs, HIV RNA and HIV DNA levels increased by 0.04 log copies/mL per year and 0.07 log copies/106 PBMCs per year during the first 8 years after diagnosis. LTNP status was lost in 36 subjects; baseline HIV DNA >1.85 log copies/106 PBMCs and high HIV DNA increase were associated with an increased risk of losing LTNP status [adjusted hazard ratio: 2.8 (1.2-6.8) and 2.2 (1.0-4.8), respectively].
Conclusions: LTNP status is established in the first years of HIV infection, low HIV DNA level at enrollment and slow increase of HIV DNA being associated with maintained LTNP status.

Racial Disparities in HIV Virologic Failure: Do Missed Visits Matter?
HIV clinic appointment adherence was worse in African Americans. Furthermore, appointment nonadherence was associated with failure to receive ARV medications and failure to achieve an undetectable HIV VL (<50 copies/mL) among patients receiving treatment. Finally, our study identifies a role of missed visits in contributing to racial disparities in virologic failure observed in African Americans. Although other factors are certainly at play on the pathway mediating racial/ethnic HIV disparities, appointment nonadherence seems to play an important role. This study highlights the need to move beyond descriptive studies of health care disparities to identify pathways that may inform interventions to address and overcome inequities for those that bear a disproportionate burden of the US HIV epidemic.

The Absence of CD4+ T Cell Count Recovery Despite Receipt of Virologically Suppressive Highly Active Antiretroviral Therapy: Clinical Risk, Immunological Gaps, and Therapeutic Options
p to 30% of human immunodeficiency virus (HIV)-infected patients who are receiving long-term highly active antiretroviral therapy do not exhibit a marked increase in the CD4+ T cell count, despite achieving complete suppression of the HIV load. These patients are referred to as "immunological nonresponders." When treating immunological nonresponders, the practicing clinician has several questions, including questions about the clinical risk associated with persistent immunodeficiency and about possible approaches to treatment that would provide clinical and immunological benefits. However, tentative answers to these questions require investigations of the mechanisms that underlie the lack of immune recovery, because only the deepest comprehension of the immunological gaps underlying functional defects will allow administration of highly targeted and efficacious treatment strategies. The aim of our review is to provide a thorough assessment of the clinical implications of a lack of increase in the CD4+ T cell count in immunological nonresponders, to examine the immunological gaps limiting recovery of the CD4+ T cell count, and to note possible therapeutic avenues, which may offer clinicians guidance regarding how to most efficaciously treat these critical patients.

Incomplete Reconstitution of T Cell Subsets on Combination Antiretroviral Therapy in the AIDS Clinical Trials Group Protocol 384
Patients in the lower baseline CD4+ strata did not achieve total CD4+ cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4+ cell count increases were similar. Ratios of CD4+ naive-memory cell counts and CD4+:CD8+ cell counts remained significantly reduced in patients with lower baseline CD4+ cell counts (<350 cells/mm3). These immune imbalances were most notable for those initiating ART with a baseline CD4+ cell count <200 cells/mm3, even after adjustment for baseline plasma HIV RNA levels.
Conclusions. After nearly 3 years of ART, T cell subsets in patients with baseline CD4+ cell counts >350 cells/mm3 achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with 350 CD4+ cells/mm3 generally did not regain normal CD4+ naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm3 and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4+ cell counts.

CD4+ T Cell Recovery with Antiretroviral Therapy: More Than the Sum of the Parts, EDITORIAL COMMENTARY
Although most HAART-treated patients may eventually achieve an optimal CD4+ T cell count outcome, an important but poorly defined subset fail to achieve this result or do so only after many years of HAART. Those patients whose CD4+ T cell counts remain low during therapy have an increased risk of a number of complications, including those due to AIDS, as well as those not traditionally thought to be HIV related (e.g., cancer, cardiovascular disease, and liver disease). The longer someone's CD4+ T cell count remains low, the higher the risk of these events. Those patients who initiate HAART with a low CD4+ T cell nadir have the highest risk of failure to achieve an optimal immunological outcome. These observations raise several important questions that investigators are now just starting to address. For example, why does HAART fail to restore normal CD4+ T cell counts in some patients? Also, why does a low CD4+ T cell count during HAART result in persistently high risk of significant morbidity, even after viral suppression has been achieved?

Increased Melanoma Rates in USA Are Real and Aging/HIV
In 2004, 7046 new cases of malignant melanoma were reported in the 13 SEER registry areas of the United States. The vast majority of cases occurred among non-Hispanic whites (N=6569, 93%), whereas 3% occurred in Hispanic whites, 1% in Asians and Pacific islanders, and less than 1% in blacks and American Indians, respectively. Melanoma affected both sexes with a male: female ratio of 3:2. Data on tumor thickness were available for 85% of cancer patients; of these, most were less than or equal to <1 mm (69%) with other thickness distributions as follows: 17% 1.01-2 mm, 9% 2.01-4 mm and 5% >4 mm.


Science Daily News


Potential New Weapon In Battle Against HIV Infection Identified
Researchers have discovered a potentially important new resistance factor in the battle against HIV: blood types. An international team of researchers from Canadian Blood Services, The Hospital for Sick Children (SickKids) and Lund University in Sweden have discovered that certain blood types are more predisposed to contracting HIV, while others are more effective at fending it off.


Defensive Protein Killed Ancient Primate Retroviruses, Research Suggests
Retroviruses are the worst sort of guest. Over eons, these molecular parasites have insinuated themselves into their hosts’ DNA and caused a ruckus. The poor hosts can’t even be rid of the intruders by killing them, because they stubbornly remain after death.


Aidsmap News

Immune system defects persist in people who start treatment late
People who started treatment with a CD4 count below 350 in a major international clinical trial were left with the immune system profile of people in advanced old age even though they appeared to have good responses to treatment, according to a report in the February 1st edition of Clinical Infectious Diseases. The findings suggest that additional immunotherapies may eventually be needed to achieve a full restoration of immune health in people taking antiretroviral therapy.
As people age, their immune systems begin to decline, losing the ability to respond to new pathogens, and the CD4:CD8 cell ratio falls, indicating that regardless of the absolute CD4 cell count, the immune system's ability is weakened.


Eureka Alert News

Mutant host cell protein sequesters critical HIV-1 element
Scientists have identified a new way to inhibit a molecule that is critical for HIV pathogenesis. The research, published by Cell Press in the January 16th issue of the journal Molecular Cell, presents a target for development of antiretroviral therapeutics that are likely to complement existing therapies and provide additional protection from HIV and AIDS.

Indiaedu News

New hope for HIV, blood cancer patients
A Canadian scientist has discovered a mechanism that stops regeneration of white blood cells that play a vital role in keeping up the body's immune system.

Medicalnewstoday News

European Commission Asks HHS To Stop Requiring Foreign Visitors To Report HIV Status To U.S. Immigration Authorities
The European Commission on Tuesday called on HHS to drop a requirement that visitors inform U.S. authorities whether they have HIV, Agence France-Presse reports (Agence France-Presse, 1/13). A law that made foreigners living with HIV/AIDS inadmissible in the U.S. was repealed when President Bush signed legislation reauthorizing the President's Emergency Plan for AIDS Relief in July 2008. HHS in 1987 placed HIV on a list of diseases barring entry into the U.S. Although that prohibition is separate from the congressionally imposed travel restrictions eased in the PEPFAR bill, federal health officials no longer were bound by law to keep HIV on the list with the signing of the PEPFAR bill. HHS in September 2008 said that it was in the process of removing HIV from the list


Other News

Aethlon Medical Nears Completion of "first-in-man" study of medical device to Treat HIV/AIDS - Quick Facts
Aethlon Medical, Inc. (AEMD.OB:  News ) announced that it is nearing completion of the "first-in-man" study of a medical device to treat Human Immunodeficiency Virus, or HIV, the disease that causes Acquired Immune Deficiency Syndrome, or AIDS.
In the study, an HIV-infected individual recently initiated treatment with the Aethlon Hemopurifier as part of a 30-day case study being conducted at the Jattinder Gambhir Hospital in Punjab, India.
The Hemopurifier is a therapeutic filtration device that serves as an artificial adjunct to the immune system.
The study goal is to demonstrate that the Hemopurifier can safely and effectively reduce viral load and trigger replenishment of CD4 immune cells in the absence of drug therapy.
The study protocol, which calls for the administration of up to twelve Hemopurifier treatments, is scheduled to be completed on January 23.

Offline John2038

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« Reply #213 on: January 18, 2009, 04:02:54 PM »
NIH News

Intracranial hemorrhage and liver-associated deaths associated with tipranavir/ritonavir: review of cases from the FDA's Adverse Event Reporting System.
Tipranavir (TPV), a protease inhibitor, has box warnings for intracranial hemorrhage (ICH) and hepatotoxicity (including hepatic failure and death). A box warning is a labeling statement about serious adverse events leading to significant injury and/or death. A box warning is the most serious warning placed in the labeling of a prescription medication. As a result of the respective morbidity and mortality associated with ICH and hepatic failure, the Food and Drug Administration's (FDA's) Adverse Event Reporting System (AERS) was searched for reports of these adverse events in HIV-infected patients receiving a tipranavir/ritonavir (TPV/r)-based regimen. This search comprised part of the FDA's safety analysis for traditional approval. From July 2006 to March 2007, 10 cases of ICH were identified in AERS. From June 2005 to March 2007, 12 cases of liver-associated deaths were identified. One patient experienced liver failure and fatal ICH. Most patients with these events had additional risk factors. Among patients with liver-associated deaths, 3 had HIV-RNA less than 400 copies per milliliter at the time of hepatic failure. Among 10 patients who discontinued TPV/r when hepatic failure developed, median number of days post-TPV/r to death was 23 (range, 2-69 days). Review of AERS did not identify new safety concerns regarding ICH. Among most patients with liver-associated deaths, death appears to occur soon after hepatic failure develops. If considering TPV/r, careful assessment of risk/benefit is suggested for patients at risk for ICH and hepatic failure.


The Hindu News

A stem cell treatment 'against AIDS'
London (PTI): Scientists claim to have achieved a major breakthrough in the fight against AIDS with a new stem cell treatment which "protects the immune system from HIV that causes the disease".
According to them, the pioneering technique involves isolating three genes which curb the spread of HIV inside the body, introducing them into human stem cells in a lab and then transplanting the stem cells into a patient's bone marrow.
"What we are doing is genetically modifying a fraction of the patient's stem cells with genes that target three diffe -rent aspects of HIV that allow it to get in the immune cells and replicate.
"When those stem cells are transplanted into patients, they create mature immune cells that circulate in the patient and protect against HIV," 'The Daily Telegraph' quoted David DiGiusto of City of Hope Medical Centre in California, where the research was carried out, as saying.
In the first human trial, the scientists transplanted anti-HIV stem cells into five AIDS patients undergoing bone- marrow replacement as part of treatment for a form of cancer known as lymphoma.
Preliminary results showed that small quantities of the transplanted stem cells were able to grow and produce new white blood cells resistant to HIV resulting in an improvement in the patients' conditions.
Now, they are planning further research to establish whether the treatment could even rid patients of HIV infection altogether.
"It is still an experimental treatment at the moment, but we hope that eventually we will be able to give AIDS pati- ents one transplant and that would then protect them for life.
We have data to show that the resistant cells are persisting in our lymphoma patients," DiGiusto said.

Metroeireann News

China criticised over HIV/drug treatment approaches
CHINA’S police and public security forces are driving drug users away from community-based prevention services and denying them access to HIV treatment, Human Rights Watch said in a report released last week.
Although China has received increasing praise for its aggressive response to the HIV/Aids epidemic in recent years, Human Rights Watch was sharply critical of its treatment of drug users.
Joe Amon, HIV/Aids programme director at Human Rights Watch, commented: “The government has expanded prevention and treatment programmes for drug users, but at the same time, the police are detaining drug users trying to access these services, and putting drug users in so-called ‘drug rehabilitation centres’ where they are provided no drug dependency treatment and no HIV prevention or treatment services.”
According to official government reports, China has three to six million drug users, and nearly half of all recent HIV transmission has been associated with drug use.
Since 2000, the Chinese government has set up more than 500 methadone treatment clinics, with the capacity to treat 100,000 drug users. Simultaneously, however, it has increasingly put drug users in mandatory rehabilitation centres, which provide no effective drug dependency treatment.
As of 2007, approximately 700 mandatory drug detoxification and 165 “re-education through labour” (RTL) centres housed at least 340,000 drug users in China. Sentences to such facilities typically range from one to three years.
Human Rights Watch found that the detoxification and RTL centres subjected drug users to abusive, inhuman, and degrading treatment, and not only failed to provide HIV prevention and treatment to drug users, but also facilitated its spread.
“The Chinese government claims that drug users are sent to these facilities for drug dependency treatment,” Amon said. “But instead of treatment they are put in overcrowded cells, denied medical care, beaten, and forced to do menial work. On top of it all, their families are forced to pay for the ‘therapy’ they receive.”
The report called on the Chinese government to close mandatory detoxification and RTL centres housing drug users and to expand voluntary community-based drug treatment and HIV prevention efforts.
Human Rights Watch also urged the United Nations agencies and international donors to support efforts to reform Chinese anti-narcotics laws and regulations, and to advocate for the rights to freedom of expression, information, assembly, and association for people living with HIV/AIDS and organisations acting on their behalf.
China has repeatedly detained and intimidated Aids activists trying to promote treatment and prevention efforts and speak out about government HIV policies.
In China, illicit drug use is an administrative offence, and Chinese law dictates that drug users “must be rehabilitated”. Chinese law requires that all patients in compulsory rehabilitation centres be provided with “medical and psychological treatment, legal education, and moral education.”
In 2007, the Standing Committee of the National People’s Congress passed a new drug law, put into effect in June 2008, which substantially restructures the detention system for individuals detained for administrative drug offences, but has significant ambiguities.
While eliminating the use of RTL centres to detain drug users, it allows up to six years of confinement for a single drug offence, with one to three years in “compulsory isolation detoxification” followed by up to three years of “community rehabilitation”.

NATAP News

Interim analysis of a double- blind, placebo-controlled study with TMC207 in patients with Multi-Drug Resistant (MDR) Tuberculosis: effective and safe

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Earth Times News

Thai officials account for 3 per cent of HIV/AIDS patients
Bangkok - Government officials accounted for 3 per cent of HIV/AIDS patients to receive treatment in Thailand over the past 24 years, health officials revealed Sunday. Public Health spokesman Suphan Srithamma said that since HIV/AIDS was first detected in the country in 1984, there were 337,989 accumulated patients at government hospitals of whom 92,111 had died, reported the Bangkok Post online news service.
He added that of the patients who received treatment for HIV/AIDS symptoms, some 10,728 were government officials, of whom 9,043 were men and 61 per cent were married.
According to a Public Health Ministry report on the 24-year history of HIV/AIDS in Thailand, the virus has infected up to 1.2 million people over the years, with the ratio of male to female victims close to two to one.
It is believed that more than half of the infected population have died although they may not have been diagnosed for HIV/AIDS or failed to receive treatment.

Mcot News

Thailand's 'People with AIDS' tally rises to 1.2 million
BANGKOK, Jan 18 (TNA) -- The lack of proper knowledge and discipline, especially among men and women buying sex services, including a significant number of Thai government civil servants, has contributed to the total number of patients contracting acquired immune deficiency syndrome (AIDS) in Thailand to rise significantly to about 1.2 million, according to a spokesman of the Ministry of Public Health.
Dr. Supan Srithamma said the Ministry's Disease Control Department believed that from 1984 through September 2008 some 1.2 million Thais of all ages and social conditions contracted the HIV-AIDS virus, including 92,111 who eventually died.
Of the total number of people-with-AIDS (PWA) during the period, more than ten thousand were government officials -- 10,278 , or 9,043 men and 1,235 women -- who suffered from the disease due to unsafe sex, Dr. Supan said, with 2,448 having died.
To reduce the number of the new infections, the Disease Control Department during the 2009 fiscal year ending September 30, will distribute 20 million condoms at-risk groups.

Offline John2038

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« Reply #214 on: January 20, 2009, 03:53:43 PM »
Unprotected sex between long-term partners with HIV: no evidence for superinfection

A study of long-term HIV-positive partners who do not use condoms when they have sex with each other has found no evidence of HIV superinfection, and instead a clear relationship between long-term frequent exposure to their partner’s virus and a strong immune response to that virus, suggesting that repeated exposures eventually build immunity against superinfection.

The findings, published in the October 2008 edition of PLoS Pathogens, a free access online journal, are important, say the University of California researchers, because of the growing practice of `serosorting` - unprotected sex between people of the same HIV status.

Current guidance for people with HIV from many sources is that unprotected sex poses a risk of superinfection – infection with a new strain of HIV that over-runs the existing virus population due to lack of immunity to that virus.

However there is limited evidence about the frequency of superinfection and little evidence that it has harmful effects even when it takes place.

Superinfection seems to happen not only in people who have been recently infected with HIV, but also in those with longstanding HIV infection. A recently reported study in Kenyan women estimated an annual incidence of superinfection of at least 4%, but no evidence of disease progression as a consequence of superinfection. A study in gay men reported an incidence of 5% per year.

Although superinfection has been associated with CD4 cell declines, and a handful of cases of transmitted drug resistance, it does not appear to have a widespread compromising effect on either the health or treatment outcomes of people with HIV.

There is much stronger evidence that unprotected sex with other HIV-infected people is harmful for people with HIV where it involves the risk of exposure to sexually transmitted infections – especially syphilis – or to hepatitis C, both of which have been on the rise among men who have sex with men in Europe and North America.

The study
Researchers from the University of California and San Francisco General Hospital examined HIV-specific T-cell responses in 49 individuals with undetectable viral load on antiretroviral therapy from a prospective cohort of HIV-positive couples receiving treatment through the Positive Health Program at San Francisco General Hospital.

Individuals were divided into two groups: those with partners who had undetectable viral load (n=29), and those with partners who had detectable viral load (n=20). There were no significant differences between the two groups in terms of relationship length, time on treatment, age, duration of infection or CD4 cell count.

Analysing T-cell HIV-specific interferon-gamma responses to various HIV epitopes (portions of viral protein that elicit an antibody response from the host), they found that significantly stronger responses to protease, reverse transcriptase and integrase peptides were detectable in those with viremic partners, with the strength of responses in this group strongly correlated with a greater frequency of unprotected sex and in particular with the frequency of receptive exposure to HIV (being the passive partner in intercourse). There was no correlation with the number of events of insertive intercourse.

There was evidence from two patients in this group whose partners started antiretroviral therapy of a subsequent decline in HIV-specific responses over the course of a year, suggesting that the control of viral load led to a loss of immune stimulus.

There was no evidence of superinfection, as measured by phylogenetic analysis of HIV DNA from patients and HIV RNA from partners.

However the authors speculate that, in order for HIV-specific immunity to be induced, a degree of superinfection must have taken place, but that it is probably confined to the mucosal surface of the body – most likely the rectum and the gut.

This phenomenon is similar to the pattern seen in exposed but uninfected sex workers, who appear to lose HIV-specific immunity if they have unprotected sex less frequently. A study in Nairobi sex workers found that women who took a break from sex work and lost HIV-specific CD8 cell responses were more likely to seroconvert subsequently, suggesting that localised mucosal infection ceased to be contained (although the study could not rule out renewed sexual exposure).

These findings suggest that even where an individual has drug-resistant virus and a detectable viral load, the risks of superinfecting an HIV-positive partner with that drug-resistant virus are low even if that partner is receptive.

The findings provide no information about what happens if an individual with HIV has receptive intercourse with many different partners with HIV, but the study’s lead author Chris Willberg, now of the Biomedical Research Centre at the University of Oxford, told aidsmap: “We would speculate that it is regular exposure to the same epitopes that is required to stimulate the responses. What we did not explore is the ability for new [epitope] responses to be developed through exposure.”

Would women exhibit the same responses if exposed to HIV from a viremic partner?

“The most logical explanation for the maintained responses that we observed is that they were driven by receptive exposure to HIV antigen derived from the viremic partner,” Chris Willberg commented. “Therefore, we would expect to see the same results in women also receptively exposed to viremic partners. If the mechanisms responsible for driving the responses in this study are the same as those that drive responses in exposed uninfected individuals, then there is plenty of evidence to suggest women would respond in a similar manner.”

Reference
Willberg CB et al. Immunity to HIV-1 is influenced by continued natural exposure to exogenous virus. PLoS Pathogens 4 (10): e1000185, 2008.

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Offline John2038

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« Reply #215 on: January 20, 2009, 03:58:18 PM »
Viral and host factors important in acute HIV infection

Two European case studies have provided insight into how viral and host factors determine the severity of primary HIV infection and early response to treatment.
While the study of virus–host interactions is in its infancy and many questions remain, the reports in the journals Clinical Infectious Diseases and AIDS support the growing evidence that HLA type may play a role in determining host response. HIV disease progression depends on many factors—some related to the virus and some related to the host. Knowing more about these factors could have many implications, from tailoring antiretroviral treatment to identifying potential targets for prevention efforts.

However, it has been difficult to tease apart the multitude of factors involved. In clinical case studies of real-life situations, two research groups from Europe have identified at least some of the viral and host factors acting during primary HIV infection. Severe acute HIV infection In an article in the January 15th edition of Clinical Infectious Diseases, Spanish investigators report two cases of severe HIV infection progressing directly to AIDS while the patients had immunological markers of acute infection.

Investigators were also able to identify the sexual partner who was the source of HIV infection in one of the cases. HIV isolated from all patients produced signs of aggressive infection in test tube assays. The virus replicated very efficiently and was able to infect cells expressing CCR5 or CXCR4 co-receptors. CXCR4-infecting virus has been linked to advanced HIV disease.
What’s more, the virus isolated in case 2 was subtype CRF02-AG, which is rare in Spain but common in West Africa and western Central Africa. The investigators write that its presence in this severe case “raises concerns about its superior replication fitness and/or transmission efficiency.”

Investigators then analysed the patients for factors that may have made them more susceptible to rapid disease progression. Human leukocyte antigen (HLA) class I is a group of proteins that play a role in the immune system’s response to infections, including HIV. Certain versions of HLA have been associated with a slower or more rapid progression of HIV disease. Upon analysis, the patient in case 1 expressed the specific HLA type HLA-B*3503, which has been reported to increase the risk of disease progression. The immune response to viral infections like HIV includes the activation of CD8 cells, also called cytotoxic T lymphocytes, however this response can sometimes fail either due to malfunction of the system or due to escape mutations developed by the virus. In in vitro tests, patient 1 showed a widespread inability to mount an adequate response HIV and another virus, Epstein Barr virus, suggesting an inherent defect in the immune response.

In case 2, there was some evidence that the lack of response may have been due to escape mutations in the virus, but the investigators could not rule out a potential defect in the patient’s immune system. Antiretroviral therapy during acute infection In a research letter published in the January 14th edition of AIDS, German researchers describes a cluster of four people in which genetic analysis of viral genomes suggested that one source person, patient A, infected two others, patients B and C, during sex.

Patient C then transmitted HIV to a fourth person, patient D. The viral genetic sequence was nearly identical between patients, with 99.6% of the genome being the same in all four isolates, suggesting transmission occurred over a short period. As part of an acute infection treatment strategy, all patients received antiretroviral therapy for six months and all achieved an undetectable viral load.

Six months after therapy was stopped, patients’ viral loads rose, with patients A and C reporting relatively high viral set points (90,000 and 600,000 copies/ml, respectively) and patients B and D reporting lower set points (7000 and 33,000 copies/ml, respectively). With nearly identical virus, the investigators reasoned that differences in responses could be ascribed to host factors, so they then analysed several markers of immune function in the four patients.

They noted that patient B carried a potentially protective version of the CCR5 receptor gene. Further more, patients B and D had versions of HLA associated with better disease control (HLA-B57 and HLA-A11, respectively). The investigators say that their data suggest that these and other host immune factors had a strong impact on the control of viral replication following cessation of therapy.

The German study was conducted in the context of antiretroviral therapy during acute HIV infection, which has yet to show concrete benefit in clinical trials, and in conclusion investigators comment that host factors such as presence of HLA-B57 should be included in trials of acute infection therapy so that the relative contribution of each can be better defined.

Reference Dalmau J et al. Contribution of immunological and virological factors to extremely severe primary HIV type 1 infection. Clin Infect Dis 48: 229 – 238, 2009. Streeck H et al. Epidemiologically linked transmission of HIV-1 illustrates the impact of host genetics on virological outcome. AIDS 23: 259 – 262, 2009.

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Re: John2038's Research News
« Reply #216 on: January 20, 2009, 11:49:34 PM »

Unprotected sex between long-term partners with HIV: no evidence for superinfection

The never-ending story...


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« Reply #217 on: January 21, 2009, 04:10:55 AM »
I think like you leit.
Now superinfection have been less debated than the Swiss Statement.

Offline John2038

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« Reply #218 on: January 21, 2009, 04:12:56 AM »
Trying a Pill to Prevent HIV
Worldwide Trials of Drug to Stem HIV Infections Raises Behavioral Questions

In a massive medical trial on three continents, doctors are testing a controversial pill that could temporarily boost immunity against HIV before a person is even exposed to the virus. If the pill works safely, doctors must then address whether such a drug, if made widely available, could actually worsen the AIDS epidemic.

The pre-exposure pill undergoing testing seems promising, since HIV drugs taken within days after exposure to the virus have been shown to reduce the risk of infection by 80 percent. But public health officials debate whether people at high risk for the virus, such as men who have sex with men, would be more likely to set aside the use of condoms to instead rely on a drug regimen that doesn't provide full protection against the disease, which is spread by contact with the blood or semen of an infected person.

Dennis, a 47-year-old gay man from Atlanta, is one of the test subjects for the new pill. He calls himself "blessed" for escaping the HIV epidemic that hit many of his friends in the 1980s. But his HIV-negative status hasn't stopped him from having sex with infected partners.

Source


China rolls out two HIV drugs to tackle resistance

BEIJING (Reuters) - China will provide two imported HIV drugs to patients who develop resistance to cheaper, domestic alternatives, state media said on Monday, going some way to meeting a key demand of AIDS treatment activists.

The decision to hand out the new drugs means that nine of 20 drugs to combat AIDS are now available to patients in China, the official China Daily said, citing senior Health Ministry official Hao Yang.

Treatment with Tenofovir, marketed by Gilead Sciences Inc under the brand Viread, and Kaletra, manufactured by Abbott Laboratories, cost over $1,500 a year each.

In comparison, the other drugs already available in China cost as little as 5,000 yuan ($730), the report added.

The new offerings come after a nationwide survey released last year showed that more than 17 percent of HIV patients in China had developed resistance to available drugs.

China estimated at the end of 2007 that about 700,000 people were infected with HIV, up from an earlier estimate of 650,000.

Although HIV infection is incurable, cocktails of the drugs can control the virus.

Nearly 60,000 people had received free HIV drugs since they were first offered in 2003, cutting the mortality rate in China from over a quarter in 2002 to just 5.8 percent in 2007, the China Daily said.

Drug-resistant HIV strains are turning up in parts of China as the virus stretches beyond high-risk groups and gains a stronger foothold in the general population, a leading Chinese AIDS researcher said late last year.

($1=6.834 Yuan)

Source

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« Reply #219 on: January 21, 2009, 09:12:12 AM »
Panacos sells HIV drug candidate

Panacos Pharmaceuticals Inc., a Watertown biotechnology company, said it has sold the rights and assets of bevirimat, a potential HIV drug, for $7 million.

The buyer is another biotech firm, Myriad Pharmaceuticals Inc. of Salt Lake City, Panacos said.

In a statement, Panacos president and chief executive Alan W. Dunton said: "Our goal has been to develop drugs with novel mechanisms of action to give people living with HIV new treatment options. In order to achieve this goal and to manage capital resources in the current market environment, we chose to sell bevirimat to Myriad Pharmaceuticals. Myriad Pharmaceuticals has the development infrastructure and financial resources that are essential both for success of the compound as it moves into late-stage clinical testing and through FDA review. Myriad Pharmaceuticals' commitment will ensure the continued development of bevirimat for the benefit of HIV-infected patients. We now turn our full attention to our other promising HIV programs and seeking additional financing and partnerships to continue the development of our spectrum of HIV programs."

To read the Panacos press release, please click here. To read the Myriad press release, please click here.

Source

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« Reply #220 on: January 23, 2009, 03:12:12 AM »
Martin Delaney


YouTube - Anthony Fauci Tribute to Martin Delaney
http://www.youtube.com/watch?v=Ud51h76u3cc

NIAID Honors AIDS Activist Martin Delaney



Martin Delaney, the founder and longtime director of the HIV advocacy/education organization Project Inform, has been presented with the National Institute of Allergy and Infectious Diseases (NIAID) Director's Special Recognition Award for his many contributions to the fight against HIV/AIDS.
 
Mr. Delaney in 1985 founded Project Inform, a leading national HIV treatment and public policy information and advocacy organization based in San Francisco, and served as its Director until 2008. He was a member of the NIAID AIDS Research Advisory Committee from 1991 to 1995, served on NIAID?s National Advisory Allergy and Infectious Disease Council from 1995 to 1998, and also has served in other advisory roles for the Institute.
 
The NIAID Director's Special Recognition Award cites Mr. Delaney?s "extraordinary contributions to framing the HIV research agenda, particularly with regard to antiretroviral drugs and access to treatment; exceptional efforts on behalf of HIV-infected people; and wise counsel while serving on NIAID advisory committees."
 
"Millions of people are now receiving life-saving antiretroviral medications from a treatment pipeline that Marty Delaney played a key role in opening and expanding," says NIAID Director Anthony S. Fauci, M.D. "Without his tireless work and vision, many more people would have perished from HIV/AIDS. He is a formidable activist and a dear friend. It is without hyperbole that I call Marty Delaney a public health hero."
 
"As a treatment advocate and activist, Marty always has been keenly analytical, well-informed, articulate, persistent, tough-minded, gracious and fair," Dr. Fauci adds. "With this award, NIAID thanks Marty for his advice, his boldness in asking hard questions (and demanding cogent answers), and for the countless hours he has devoted to helping NIAID, formally and informally, in our work in the fight against HIV/AIDS."
 
Mr. Delaney was one of the founders of the community-based HIV research movement and, through his work at Project Inform, led the way to HIV treatment education becoming widely available to patients and medical providers.
 
He was a leader of the movement to accelerate Food and Drug Administration approval of promising drugs and a key player in the development of today's widely used Accelerated Approval regulations and Parallel Track system for providing experimental drugs to seriously ill people preceding formal FDA approval.
 
In recent years, among many other activities, Mr. Delaney has led the Fair Pricing Coalition to improve the accessibility of HIV medications, and has advocated for an aggressive research agenda to find a cure for AIDS.
 
For further information about Martin Delaney or Project Inform, please contact Ryan Clary at 415-558-8669 or rclary@projectinform.org.

Offline John2038

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« Reply #221 on: January 23, 2009, 03:17:51 AM »
ScienceDaily News

Excessive Weight Loss Can Be A Bad Thing
Doctors are not doing enough to pick up on problems with excessive weight loss, says a Saint Louis University physician who helped draft recent guidelines to diagnose the condition called "cachexia" (kuh-kex-ee-uh).

"In sick people, weight loss is an important indicator of disease and potentially impending death," said John Morley, M.D., an endocrinologist and director of the division of geriatric medicine at Saint Louis University School of Medicine.

"Cachexia is an extraordinary problem for people who are having other health problems, yet this is something that many physicians don't pay attention to."

A group of physicians and scientists agreed on a definition of cachexia, which was published in the December edition of the medical journal, Clinical Nutrition.

"The definition is important because it gives physicians the guidelines to make a diagnosis and treat the condition," Morley said. "A definition of cachexia also makes it easier for scientists to conduct research and potentially develop new therapies for the problem."

About half of hospitalized patients and between 10 and 15 percent of sick patients who see a doctor have cachexia. The condition accompanies diseases such as cancer, congestive heart failure, HIV, diabetes, kidney failure and COPD (chronic obstructive pulmonary disease).

Adults with cachexia lose weight and children don't grow. Muscle mass melts away, and those with cachexia also may lose fat.

Those who traditionally have had difficulty taking off weight and suddenly find the pounds melting off should beware, Morley said. They may be ill and could get even sicker as they become weaker and weaker.

"Cachexia should be seen as a wasting disease that requires specialized treatment from a physician who is familiar with the problem," Morley said.

The researchers clarified the definition of cachexia by noting it is always linked to an underlying disease. They differentiated it from starvation; loss of muscle mass that comes with aging; depression; thyroid problems; and the body's difficulty in absorbing nutrients. Rather, cachexia is a complicated metabolic syndrome that is often associated with anorexia, inflammation, insulin resistance and increased muscle protein breakdown.

NATAP News

Once-Daily HAART Modestly Beats Twice-Daily on Adherence & Viral Suppression: meta-analysis
Our meta_analysis found that the rate of adherence to once-daily antiretroviral regimens was better (+2.9%) than the rate of adherence to twice-daily regimens. To our knowledge, this is the first attempt to quantify, in a meta_analysis, the effect of dosing schedule on adherence to antiretroviral therapy. This effect was greater for patients who were initiating treatment than for those receiving stable therapy who were observed in "switch" studies.

Reduced susceptibility to lamivudine and emtricitabine associated with the novel K66N mutation in HIV-1 reverse transcriptase
The drug resistance profile of K66N, a novel mutation in HIV-• 1 reverse transcriptase (RT HIV-1 reverse transcriptase (RT), is identified as a result of discrepant phenotype/genotype results.

The rare mutation K66N in HIV-1 RT is associated with reduced phenotypic susceptibility to 3TC and FTC and not to the other NRTIs.
 
Further research is required to investigate the clinical impact of this finding, how the mutation evolves and whether it is selected during a specific therapy.

HIV Prematurely Accelerates Aging
HIV-1 infection induces premature aging of both memory T cells and naive CD4+ T cells; in particular, the fast progressors (FPs) experience accelerated aging of lymphocytes.....Whether highly active antiretroviral therapy can reverse or retard this process is not yet clear and needs to be investigated, although 1 study has shown that accumulation of aged T cells continues in highly active antiretroviral therapy-treated patients with increased CD4+ T cells and long-term viral suppression

Effects of Omeprazole on Plasma Levels of Raltegravir
Overall, the data support the use of raltegravir in patients receiving gastric pH-altering agents with no dosage adjustment. Further investigation is necessary to more fully characterize the pharmacokinetics of raltegravir given in combination with gastric pH-altering agents in HIV-1-infected patients.



Persistent Minority K103N Mutations among Women Exposed to Single-dose Nevirapine and Virologic Response to Nonnucleoside reverse-Transcriptase Inhibitor-Based Therapy
"K103N mutations were detected by AS-PCR in 10 (10.6%) of 94 sdNVP-exposed women before they commenced treatment; the mutations were detected in viral RNA for 10 women (10.6%) and in viral DNA for 3 women (3.2%). K103N mutations were also detected by AS-PCR in 9 (15.0%) of 60 sdNVP-unexposed women before treatment; they were detected in viral RNA for 8 women (13.3%) and in viral DNA for 3 women (5.0%). Samples with the highest percentages of K103N mutations detected by AS-PCR also had K103N mutations detected by population sequencing (table 3)....Detection of K103N mutations by AS-PCR before treatment was a strong predictor of inadequate virologic response (table 4)."
 
"In conclusion, 10%-15% of women with previous pregnancies who enter treatment programs have resistance mutations that triple the chances that they will not maintain viral suppression while receiving NNRTI-based therapy. This proportion is sufficiently small such that there are no detectable consequences of sdNVP exposure that has occurred 18-36 months previously. To ensure that only few pregnant women will require therapy in the months that follow delivery, we recommend that eligible pregnant women be screened and commence effective antiretroviral therapy."


Single-Dose Nevirapine to Prevent Mother-to-Child Transmission of HIV Type 1: Balancing the Benefits and Risks
The question of whether there is a long-term increased risk of virologic failure among women who have received sdNVP treatment still remains to be answered.....the article by Coovadia et al. adds to the growing body of evidence that low-frequency drug-resistant variants are important determinants of response to antiretroviral therapy

CDC Updates New HIV Cases Surveillance Estimates: "the disease continues to affect the MSM population more than any other in the United States"
The distribution of new HIV infections in 2006 demonstrates that, more than 25 years after the first report of AIDS, the disease continues to affect the MSM population more than any other in the United States.....the age distribution of persons with new infections suggests important differences by race and ethnicity. Among black and Hispanic MSM, most new infections were in persons aged 13-29, whereas, among white MSM, most new infections were in persons aged 30-39 years.....new infections of HIV occurred disproportionately among blacks and Hispanics.2 The results in this report indicate further that the disparity between racial/ethnic minorities and whites is greatest among females......comprehensive surveillance systems are essential for HIV incidence estimation. All states are now implementing confidential, name-based HIV surveillance, and national data on HIV diagnoses and incidence likely will continue to improve.....CDC supports state and local health departments and community-based organizations to promote effective HIV prevention interventions that target those persons at greatest risk for HIV infection.

Medicalnewstoday

Topical Treatment Wipes Out Herpes With RNAi
Harvard Medical School professor of pediatrics Judy Lieberman, who is also a senior investigator at the Immune Disease Institute, has overseen the development of a topical treatment that, in mice, disables key genes necessary for herpesvirus transmission. Using a laboratory method called RNA interference, or RNAi, the treatment cripples the virus in a molecular two-punch knockout, simultaneously disabling its ability to replicate, as well as the host cell's ability to take up the virus.

Advocates Calling On Obama Administration To Make Changes In U.S. Global Policy, Including HIV/AIDS Issues
Some advocates are calling on President Obama's administration to change the nation's approach to global social and health issues, including HIV/AIDS, the Washington Post reports. According to the Post, the efforts are part of a push by advocates to "transform the way the United States deals with matters of sex, marriage and religious values in the international arena," which "will play out in upcoming United Nations conferences and meetings that set international norms on issues including human rights, public health, family planning and HIV/AIDS." Joseph Amon, head of the HIV/AIDS and Human Rights Program at Human Rights Watch, said that although President George W. Bush made significant investment in global efforts against HIV/AIDS, the programs relied too heavily on abstinence-based initiatives. Amon said, "If we want to have an impact on the AIDS epidemic, we cannot allow moral ideological consideration to trump scientific evidence and human rights." The Post reports that some liberal advocates anticipate the Obama administration will "pursue a cautious pace" in making global policy changes and some social conservatives "are bracing for a long period in the political wilderness" (Lynch, Washington Post, 1/18).

Abcnews

Iranian AIDS Doctors Get Several Years in Jail
Iran has sentenced two internationally renowned Iranian AIDS physicians to six and three years in prison for their alleged participation in a U.S.-backed plot to overthrow Iran's Islamic regime, their lawyer said Thursday.

Aidsmap News

HIV-positive patients with lung cancer have improved prognosis with HIV treatment
HIV-positive patients with non-small-cell lung cancer have a significantly better progress if they take HIV treatment, French researchers report in the online edition of the journal Lung Cancer. Patients who took HIV treatment had an average survival of nine months compared to little over four months for individuals who did not take anti-HIV drugs.

The life-expectancy of HIV-positive patients has improved dramatically since effective HIV treatment became available. However, several studies have shown that non-HIV-related cancers are an increasingly important cause of illness and death in people with HIV.
« Last Edit: January 23, 2009, 04:36:16 PM by John2038 »

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« Reply #222 on: January 23, 2009, 04:39:58 PM »
Stem-cell-based therapy

FDA OKs Geron's first-ever stem-cell treatment trials

Geron Corp said Friday that the U.S. Food and Drug Administration has granted clearance for it to begin trials for what it said was the world's first study of a human embryonic stem cell-based therapy for people. Geron said it will begin a Phase I multicenter trial designed to establish the safety of its treatment, currently referred to as "GRNOPC1," in patients with complete Grade A subacute thoracic spinal cord injuries.

Details
The Food and Drug Administration has granted clearance of an investigational new drug application that lets Geron Corp. move forward with the world’s first study of a human embryonic stem-cell-based therapy in humans.

Menlo Park, Calif.-based Geron (NASDAQ: GERN) said it plans to initiate a Phase I multicenter trial that is designed to establish the safety of the drug GRNOPC1 in patients with spinal cord injuries. The stem cells are licensed from the Wisconsin Alumni Research Foundation, the patent and technology licensing arm of the University of Wisconsin-Madison.

“Today’s news is a significant milestone in the translation of new discoveries in cell biology into life saving cures,” said Ed Fallone, president of Wisconsin Stem Cell Now. “It underscores the amazing potential of embryonic stem cell research to transform the lives of thousands of Wisconsinites and their families who struggle with chronic disease and disability.”Wisconsin Stem Cell Now in Shorewood is a not-for-profit, grassroots organization supporting stem cell research.

Geron said the treatment contains progenitor cells that have demonstrated the ability to stimulate nerve growth.

The company said that although the trial's goal is to demonstrate safety, a secondary goal is to look at efficacy, such as "improved neuromuscular control or sensation in the trunk or lower extremities."

The FDA reviewed the proposal from Geron for over a year before deciding to authorize it, Wisconsin tem Cell Now said in a press release. The study will focus on the safety of embryonic stem cell treatments as well as their effectiveness.

Embryonic stem cell research, which has been severely limited by the federal government since an executive order from former President Bush in 2001 restricted federal funding, has the potential to cure not only physical ailments like spinal cord injuries, but diseases like Parkinson’s, Alzheimer’s, and diabetes.



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« Reply #223 on: January 24, 2009, 12:25:22 AM »
sciencedaily

Potential New Antibody Treatment For Autoimmune Diseases
Scientists at UCSF have discovered an abnormality in a patient’s immune system that may lead to safer therapies for autoimmune diseases such as rheumatoid arthritis and colitis, as well as potential new ways to treat transplant rejection.

oetzl’s team evaluated a woman with a low number of blood T cells and frequent infections in the ears, urinary tract and lungs. The infection of several organs suggested a defect in the patient’s immune system similar to Acquired Immune Deficiency Syndrome (AIDS), but the patient tested negative for human immunodeficiency virus (HIV).

Further studies revealed that the patient’s CD4 T cells did not move out of her lymph nodes as they would in a normal immune system because her body created antibodies to one type of sphingosine 1-phosphate (S1P) receptor. S1P is critical to appropriate immune responses since it regulates T- and B-cell movement throughout the body by interacting with its receptor. The patient’s antibodies blocked the signaling that triggers T-cell movement from the thymus and lymph nodes into blood and then into many organs.

Researchers then explored whether the woman’s antibodies effectively could inhibit an autoimmune response in mice. Antibodies against the S1P receptor, created from the patient’s antibody-producing cells, were injected into mice that were induced to develop colitis. The result was a significant reduction in severity of their diseases, including colitis-associated weight loss, in those mice compared to mice that did not receive the antibodies.

“These results have broad biological implications, since the cells that carry out our immune responses are present in every organ,” said Goetzl, director of UCSF Allergy and Immunology Research, which focuses on developing new diagnostic approaches and treatments for allergic and immunological diseases.

eurekalert

STDs disrupt genetic bottleneck that usually constrains HIV infection
Scientists have shown that HIV faces a genetic "bottleneck" when the virus is transmitted heterosexually from one person to another, by way of the genital mucosa. The results, published January 23 in the open-access journal PLoS Pathogens, explain why prior infection by other sexually-transmitted diseases (STDs) makes individuals more susceptible to HIV infection.

The team of researchers, lead by Eric Hunter of Emory University, identified 20 heterosexual couples soon after infection occurred and obtained viral genetic sequences from both partners. They examined the most variable region of the virus' env gene, which encodes a protein forming the outer coat of the virus. Approximately 90% of the couple recipients were found to be infected by a single viral variant of HIV-1. However, that variant was not the same in each case.

For comparison, the researchers also analyzed a group of newly infected individuals who were infected by someone other than their spouse. This group showed more variety in viral sequences, with 3 out of 7 individuals infected by multiple variants. Overall, out of 42 newly infected people studied to date, all five infected by multiple viral variants had evidence of genital inflammation or ulceration.

In these cases, it appears that the bottleneck was enlarged due to the disruption of normally protective mucosal barriers by STDs. These findings suggest that the genital mucosa provides a natural barrier to infection by multiple genetic variants of HIV-1 that can be lowered by inflammatory genital infections.

To identify newly infected individuals, the team collaborated with public health programs directed by Susan Allen of Emory's Rollins School of Public Health that enroll thousands of heterosexual couples with one HIV-positive partner in Rwanda and Zambia.

medicalnewstoday

ABC News Examines Pre-Exposure Prophylaxis For HIV Prevention
According to Albert Liu, director of HIV prevention intervention studies at the San Francisco Department of Public Health, there have been "reports that people may be using PrEP out in the community before it was in trial." To investigate this possibility, Liu and colleagues conducted studies in three cities in California involving 1,800 MSM. Of the men questioned, 16% reported having heard of antiretroviral use to prevent HIV transmission and 1% admitted trying PrEP on their own. In addition, a similar study of more than 227 men in Boston found that one person reported using PrEP drugs instead of a condom. However, despite the low reported rates of PrEP use outside clinical trials, some advocates worry that the number of people substituting such drugs for condoms could increase if FDA approves a PrEP regimen. Sean Strub, founder of POZ Magazine, said that the "problem" with PrEP drugs is the idea that they could act as a "disinhibitor" and thus discourage people from practicing safer sex. According to Liu, the "important thing to realize is that [PrEP is] not just an evening-before pill that people pop." Strub added that members of the community could become involved in encouraging safer sex to prevent HIV transmission.

Dana Van Goder, executive director of Project Inform, said PrEP drugs could be "costly," ranging from $500 to $900 monthly. However, prices for the drugs could decrease if the medications became more widely available, Van Goder said. According to ABC News, Liu currently is leading a trial of the drug Truvada among 3,000 men in the U.S., South America, Asia and Africa. Liu said the daily pill could have side effects such as kidney or liver damage, adding that the study participants need routine HIV testing and follow-up services. "These are men who are at risk for HIV," Liu said, adding that "since we don't know whether [PrEP] works, we want to keep them on the best prevention" (Cox, ABC News, 1/20).

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« Reply #224 on: January 24, 2009, 07:16:46 AM »
what is Q1 09 ?
God grant me the serenity to accept the things i can not change.

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« Reply #225 on: January 24, 2009, 08:09:37 AM »


Q1-09 --- means the first quarter of the year 2009 (Jan,Feb,Mar).

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« Reply #226 on: January 27, 2009, 04:19:37 AM »
Aethlon Medical Completes First Medical Device Study to Treat HIV/AIDS

SAN DIEGO —  Aethlon Medical, Inc. (OTCBB:AEMD) announced today that it has completed the “first-in-man” study of a medical device to treat Human Immunodeficiency Virus (HIV), the disease that causes Acquired Immune Deficiency Syndrome (AIDS). In the study, an HIV-infected individual completed a twelve treatment study of the Aethlon Hemopurifier® administered thrice weekly over the course of 30-days. The Hemopurifier® is a therapeutic filtration device that serves as an artificial adjunct to the immune system. In HIV care the Hemopurifier® targets the clearance of all circulating strains of infectious HIV, including those varieties that cause patients to fail antiviral drug regimens. Additionally, the device assists to preserve immune response through the removal of gp120 and other toxic proteins shed by HIV to kill-off immune cells, the hallmark of AIDS. The study was conducted at the Sigma New Life Hospital in Punjab, India. Initial viral load and immune cell data resulting from the study are expected to be available for disclosure in mid-February.

“Based on previous treatment outcomes in Hepatitis-C patients, we are cautiously optimistic that the data resulting from our first HIV study will also prove to be positive,” stated Jim Joyce, Chairman and CEO of Aethlon Medical. “The principal investigator of our study has reported all twelve Hemopurifier® treatments were completed without any observed adverse events, and that the patient feels an improved sense of well being, including increased energy and appetite,” concluded Joyce.

In a previous infectious disease study, treatment with the Hemopurifier® resulted in robust viral load reductions in Hepatitis-C (HCV) infected patients who completed a treatment protocol of three, 4-hour Hemopurifier® treatments every other day during the course of one week. The Study was conducted at the Fortis Hospital in Delhi, India.

Patient #1 had a 95% reduction three days post treatment and 89% reduction seven days post treatment. The initial viral load for patient 1 was 5.3 x 10(5) viral units per ml of blood (IU/ml). Patient 1’s viral load seven days post treatment was 5.7 x 10(4) IU/ml.

Patient #2 had a 85% reduction three days post treatment and 50% reduction seven days post treatment. The initial viral load for patient 2 was 9.2 x 10(6) IU/ml. Patient 2’s viral load seven days post treatment was 4.6 x 10(6) IU/ml.

Patient #3 had a 60% reduction three days post treatment and 83% reduction seven days post treatment. The initial viral load for patient 3 was 3.0 x 10(8) IU/ml. Patient 3’s viral load seven days post treatment was 5.1 x 10(7) IU/ml. All viral load measurements were performed with real-time quantitative polymerase chain reaction (RT-PCR). Control samples were measured in duplicate while treatment samples were generally measured in triplicate.

Source
« Last Edit: January 27, 2009, 04:21:47 AM by John2038 »

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« Reply #227 on: January 27, 2009, 04:25:23 AM »
New study

Discordance: experts study prevention of infection

A clinical trial on preventing the spread of HIV among discordant couples (where one person is HIV-positive and the other is negative) is going on. The Pre-Exposure Prophylaxis (PrEp) strategy involves administering a pill to an HIV-negative partner in a relationship to prevent them from contracting the virus. The Infectious Disease Institute is conducting the study. Elvis Basudde interviewed Dr. Edith Nakku, the coordinator of the study

What is PrEp about?

There is scientific evidence that Tenofovir (Viread) and the combination of Tenofovir plus Emitricitabine (Truvada), if taken daily as preventive therapy, might substantially reduce the risk of contracting HIV.

This approach is known as pre-exposure prophylaxis (PrEp). Pre means before exposure to contact with HIV and Prophylaxis is about taking medication to prevent infection.

Why conduct the study?

A safe and effective approach to preventing new HIV infections is needed urgently. Each day, nearly 11,000 peopleworldwide get infected with the virus. Most of them live in Africa.

The traditional prevention methods include abstinence, being faithful to one's sexual partner, and using condoms. However, not everyone is able to use these methods. The majority of HIV infections in Africa occur among women.

The current prevention methods are inadequate, since women often do not have social or economic power to refuse sex or negotiate condom use. A vaccine against HIV is most likely to be availed in 10 years' time, so a new prevention strategy must be found.

How might PrEp protect against HIV infection?

The idea of medication that prevents infection is old. For instance, mothers who are living with HIV take medication during pregnancy to prevent them from passing the virus on to their unborn babies.

This is key because the medication gets into the bloodstream before one is exposed to infection. It also helps to prevent infection from occurring. If the PrEp medication is already in the bloodstream, when one is exposed to the virus, it would not be able to establish itself, so infection would not occur.

Is PrEp different from ARVs?

A person who is HIV-negative takes PrEp medication to prevent them from contracting HIV, whereas ARVs are given to people living with the virus, to decrease the amount of virus.

What studies on PrEp are being done?

Seven studies are being carried out in Africa, Asia, South America and the US. They will involve more than 15,000 participants, who will have to be in stable relationships or married.

How does discordance occur?

Studies in Africa have found that the partner of an HIV-infected person has a 50% chance of being infected, even if the couple has been together for several years. The factors include higher HIV levels, genital herpes and the male partner being uncircumcised.

Many couples have been in relationships for years and may not know each other's HIV status. In spite of this, however, the uninfected partner in a discordant relationship can still become infected.

In fact, stable couples that are HIV discordant are thought to account for the majority of new HIV infections among adults in Africa.

How is the PrEp study designed?

It will include about 3,900 discordant couples, enrolled at eight clinical sites in Uganda and Kenya. The study is random and the participants, who are HIV-positive, will be randomly divided into groups. All participants will take their medication everyday. One group will take tenofovir; the second, a combination of emtricitabine and tenofovir; and the third will take a placebo.

What is a placebo?

It is an inactive pill that has no medicine in it that looks or tastes like tenofovir or emtracitibine. In research studies, the medicine being tested is compared with a placebo to see if the effects are truly due to the medication or merely chance.

The placebo is necessary because there is no evidence that PrEp can prevent HIV infection, so there is need to study the number of participants who get infected with HIV during the study.

Who can take part?

The study will enroll voluntary HIV discordant couples who are sexually active. To protect the health of the participants, both the HIV-negative and positive partners must meet the eligibility requirements.

The uninfected partner must be healthy, with a normal liver, kidney and blood count tests and cannot take medication that might interfere with the medication. The uninfected partner should not be pregnant or breastfeeding.

The infected partner must also be in good health, having a CD4 count of over 250 cells and ineligible for treatment with HIV. Participants will be studied for about three years.

What happens if a participant becomes pregnant?

Tenofovir and emtricitabine/tenofovir have been used safely by HIV-infected pregnant women, and animal studies have shown that these medications do not harm the unborn baby.

However, there is little experience with these drugs to tell if they are safe for pregnant women.

As a result, family planning services will be provided for all participants. Women taking the trial medication will have pregnancy tests at every monthly visit, so that pregnancy can be detected early.

If a woman taking study tablets becomes pregnant, the study medication will be stopped, but she will still continue taking part.

Source

Offline sensual1973

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« Reply #228 on: January 27, 2009, 10:46:58 AM »
what are the most promissing studies out there dealing with hiv eradication or a cure ? - am not talking preventive therapy here.
thanks
God grant me the serenity to accept the things i can not change.

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Re: John2038's Research News
« Reply #229 on: January 27, 2009, 03:56:24 PM »
what are the most promissing studies out there dealing with hiv eradication or a cure ? - am not talking preventive therapy here.
thanks

Few point of views:

http://forums.poz.com/index.php?topic=24510.0

Offline John2038

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« Reply #230 on: January 28, 2009, 04:13:16 AM »
City of Hope’s stem cell treatment shows promise against AIDS

DUARTE, Calif. —Working with four lymphoma patients whose bone marrow had been killed via chemotherapy, a team led by Dr. David DiGuisto, director of haematopoietic cell therapies at City of Hope Medical Center in Duarte, Calif., has demonstrated promising results from subsequent treatment with genetically altered stem cells. The scientists are planning further research to establish whether the treatment might rid patients of HIV infection altogether.

The technique involves introducing genes that curb the spread of HIV inside the body into human stem cells, then transplanting the stem cells into a patient’s bone marrow. In the first human trial, anti-HIV stem cells were transplanted into the four AIDS patients undergoing bone marrow replacement as part of treatment for lymphoma. The stem cells, DiGuisto says, are a mixture of genetically altered cells and “a sufficient dose of unmanipulated stem cells.” The protocol calls for no less than 2 million cells per kilogram of body weight. “Our best estimate,” DiGuisto adds, “is that about one percent of the cells are of the genetically altered type.” All four infused patients are in remission for lymphoma with no recurrence of HIV.

Presenting his finds from the trial at the Stem Cell World Congress in Palm Springs, Calif., DiGuisto described his work as “A first-in-humans study of safety and feasibility of stem cell therapy for AIDS lymphoma using stem cells treated with a lentiviral vector encoding multiple anti-HIV RNAs.” Unanswered at this time is the fate of the 99 percent of the stem cells that were infused without the protecting treatment. The hope is that, in a sort of “survival of the fittest” at the cellular level, the treated stem cells will proliferate and take over.

“We are currently doing two things to improve the process,” DiGuisto says. “First, we are seeking approval of a protocol to introduce 100 percent of the modified stem cells. A second approach would be to introduce the same modified genes into T-lymphocytes of HIV patients. We have data to show that the resistant cells are persisting in our lymphoma patients. It is still an experimental treatment, but we hope that eventually we will be able to give AIDS patients just one transplant that would protect them for life.”

The next step is to repeat the first-in-human trial in five to 10 patients, DiGuisto adds, and then to increase the cohort to between 30 and 50 individuals.

Source

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« Reply #231 on: January 28, 2009, 04:48:21 AM »
Heart Association Recommends Daily Intake of Omega-6 Fatty Acids

At least 5% to 10% of daily caloric intake should come from omega-6 fatty acids, according to an American Heart Association science advisory that emerged from a literature review.
 
Consumption of this level of omega-6 polyunsaturated fatty acids was associated with a reduced risk of coronary heart disease, William S. Harris, Ph.D., of the University of South Dakota, and colleagues reported in the advisory, published in the Feb. 17 issue of Circulation: Journal of the American Heart Association.
 
"Aggregate data from randomized trials, case-control and cohort studies, and long-term animal feeding experiments indicate that the consumption of at least 5% to 10% of energy from omega-6 fatty acids reduces the risk of coronary heart disease relative to lower intakes," the researchers said.

Other health organizations have set recommendations for omega-6 fatty acid intake. The European Commission recommendation is 4% to 8%, the World Health Organization suggests 5% to 8%, and some North American dietetic associations say 3% to 10%. The AHA had no previous recommendation.
 
Some research, however, has suggested that omega-6 fatty acids may actually increase cardiovascular risk because they promote inflammation. Concern stems from the fact that the primary omega-6 in food is linoleic acid, which can be converted to arachidonic acid -- a substance involved in the early stages of inflammation.
 
So the researchers reviewed a meta-analysis of randomized controlled trials involving omega-6 intake and several other observational, cohort, and case-control studies.
 
Most studies, they said, found omega-6 fatty acids were associated with unaltered or lower levels of inflammatory markers. Two studies showed no effects on any metabolic parameter or platelet function, and Dr. Harris noted that conversion of linoleic acid to arachidonic acid is only about 0.2%.
 
For overall disease risk, one meta-analysis evaluated several randomized controlled trials.
 
In addition to the inability to double-blind these studies, many had design limitations such as small sample size, the provision of only approximately 50% of meals, outcomes composed largely of "soft" ECG endpoints, randomization of sites rather than individuals with open enrollment and high turnover, and simultaneous recommendations to increase fish and cod liver oil.
 
Nevertheless, a meta-analysis of six of these trials indicated that replacing saturated fatty acids with omega-6 fatty acids lowered the risk for coronary heart disease events by 24%.
 
The researchers said that the reviewed prospective cohort studies found an "overall modest benefit of omega-6 polyunsaturated fatty acid intake on coronary heart disease risk and no significant effect on stroke or cancer."
 
One meta-analysis of 25 case-control studies found linoleic acid content was inversely associated with coronary heart disease risk, while arachidonic acid was unrelated to risk.
 
As for disease markers, the researchers said the cholesterol-lowering effect of linoleic acid "is well established in human trials." One meta-analysis of 60 feeding studies including 1,672 patients found the nutrient lowers levels of LDL cholesterol.
 
"Favorable effects of linoleic acid on cholesterol levels are thus well documented and would predict significant reductions in coronary heart disease risk," the researchers said.
 
Linoleic acid cannot be synthesized by humans, but comes primarily from vegetable oils such as corn and sunflower oil.
 
Dr. Harris said the U.S. daily intake of omega-6 fatty acids is typically about 6% of total calories -- about 120 kcal (13 g) in a 2,000 kcal diet.
 
To measure their intake, patients should look for the polyunsaturated fat listing on products' Nutrition Facts Panel, which is virtually all omega-6 fatty acids, Dr. Harris said.
 
Companies, however, are only required to list total fat broken down into saturated fat and trans fat. If polyunsaturated fats are not listed, there's no way to distinguish the amount of omega-6 fatty acids because the "unsaturated fats" listing includes monounsaturated fats as well as polyunsaturated fats, he said.
 
While the recommended intake of omega-6 fatty acids is now 5% to 10%, Dr. Harris noted preventing coronary heart disease must be in the context of an overall healthy diet.

Source

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« Reply #232 on: January 28, 2009, 02:39:50 PM »
New Australian vaccine could stop cancers


AUSTRALIAN researchers are confident they can create the "holy grail" of cancer prevention with a multi-purpose vaccine.

The team from the University of South Australia is working on a vaccine that would prevent one in five cancers by eliminating the infections that cause them.

Chronic infections such as human papillomavirus, hepatitis B and HIV can lead to a range of deadly cancers, The Advertiser reports.

Team leader and senior immunology lecturer Dr John Hayball is working on the project in conjunction with Associate Professor Michael Brown from the Royal Adelaide Hospital's Hanson Institute.

He said that while work was now in the "pre-clinical and experimental" phase, the "ultimate aim" was not just to prevent the cancer-causing infections but to cure the existing ones.

"We're trying to make therapeutic vaccines, so instead of making vaccines that just protect you from getting an infection - these vaccines will also do that - the idea is to actually kill the diseases that people carry," Prof Hayball said.

"We're trying to develop a platform technology that can be used for any number of chronic viral diseases, a lot of which are associated with causing cancer.

"If we can eliminate those infections, there's a real possibility of cutting the incidence of cancer by one fifth and obviously that's a huge leap forward."

The vaccine would be administered via injection and would be carried by a safe, non-pathenogenic virus.

The most high-profile vaccine to be developed recently is Gardasil.

It works by protecting against the HPV infection, which causes 70 per cent of cervical cancers.

Gardasil's creator, Professor Ian Frazer, is now working on a vaccine for skin cancer.

Dr Hayball said the team wanted to make a vaccine that would go to the next level.

"(The Gardasil) vaccine, like all vaccines today, can only protect you from getting the virus, once you've got it it's too late," he said.

The Cancer Council's SA chief executive, Associate Professor Brenda Wilson, said the news was an exciting advance in the battle against cancer.


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Offline sensual1973

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Re: John2038's Research News
« Reply #233 on: January 29, 2009, 12:05:30 PM »
so the research at the "city of hope medical centre" is to eradicate the virus or curb it and prevent  aids ? - see how can one word change the whole meaning of a certian study !
God grant me the serenity to accept the things i can not change.

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« Reply #234 on: January 29, 2009, 01:05:40 PM »
NATAP News

New Norvir Tablet Application Submitted to FDA by Abbott

January 21, 2009
 
Abbott is pleased to announce that it has submitted applications seeking registration for a new tablet formulation of our protease inhibitor (PI) Norvir (ritonavir) with U.S. and E.U. regulatory authorities. This new formulation will not require refrigeration, which will make its use more convenient, particularly in developing countries where the majority of people with HIV live.
 
Abbott's development of the Norvir tablet is the result of the efforts of our scientists to address the needs of people living with HIV. Abbott scientists tested multiple formulations before developing and submitting the final formulation for regulatory consideration. The Norvir tablet was developed using Meltrex technology, which is also used in Abbott's Kaletra (lopinavir/ritonavir) tablets. Even with the use of Meltrex technology, ritonavir had unique formulation requirements to ensure stability and absorption. Abbott first presented data from a pivotal bioavailability study of the tablet, which compared the new formulation to the current Norvir soft gel capsule, at the XVII International AIDS conference in Mexico City (AIDS 2008) in August 2008.
 
Norvir is indicated in combination with other antiretroviral agents for the treatment of HIV infection. Kaletra is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
 
Abbott intends to register the new Norvir tablet formulation broadly worldwide. We look forward to continuing to work with the HIV community to improve the lives of individuals with HIV.
 
If I can provide further information or address any questions you may have, please do not hesitate to contact me.
 
Jim Howley
Director, Advocacy and Policy, Abbott
 
Please see below for the Indication and Important Safety Information about Norvir and Kaletra in combination therapy.

Please click here for Norvir full Prescribing Information
http://www.norvir.com/
 
Please click here for Kaletra full Prescribing Information
http://www.rxabbott.com/pdf/kaletratabpi.pdf

Ultrasensitive Assessment of Residual HIV Viraemia in HAART-Treated Patients With Persistently Undetectable Plasma HIV-RNA: A Cross-Sectional Evaluation

Improvements in HIV-RNA assays have made accurate detection of as few as 2 copies/ml possible. This study objective was the evaluation of ultrasensitive HIV-RNA quantitation (beneath current threshold: 50 copies/ml) in patients receiving different antiretroviral regimens. A cross-sectional, ultrasensitive measurement of HIV-RNA levels (detection limit: 2.5 HIV-RNA copies/ml) was performed in 154 HIV-1-infected patients receiving ARV therapy, all classed as full responders according to the 50 copies/ml cut-off. Patients were undergoing treatment with two nucleoside/nucleotide reverse transcriptase inhibitors (N/NtRTIs) plus nevirapine (NVP, n1/448), efavirenz (EFV, n1/457) or lopinavir/ritonavir (LPV/r, n1/449). Undetectable HIVRNA (<2.5 copies/ml) occurred in 29/48 (60.4%), 24/57 (42.1%) and 14/49 (28.6%) NVP, EFV and LPV/r recipients, respectively. Mean virologicalsuppression (<50 copies/ml) duration was 28.6 months (median1/422, SD1/417.8), and only in LPV/r recipients length of suppression was associated with significantly lower HIV-RNA levels (P1/40.015). Mean nadir CD4+ cell count of 270 cells/mm3 (median1/4240, SD1/4194.5) was significantly lower in the LPV/r arm (P<0.001). Nadir CD4+ level correlated with virological suppression but had opposite trends between NVP (positive) and LPV/r (negative; two tailed P1/40.01). Logistic regression analysis showed NVP was the only independent factor associated with virologic suppression. NVP has demonstrated a distinct virological advantage at subclinical viral loads, possibly due to its greater penetration in extra-vascular compartments, warranting further investigation in the context of persistent low-level viraemia in long-term HAART.

Among patients with HIV infection who achieved virological suppression on HAART, those receiving NVP-based regimens were able to exert a more profound inhibition of viral replication (observed below the currently adopted threshold of virological suppression) than those receiving EFV- or LPV/r-based regimens. The clinical importance of this finding deserves further study in the context of persistent low-level viraemia under long-term HAART and the impact of antiretroviral penetration into long-lived reservoirs of virus.

Aidsmap News

Study suggests that HIV infection and use of antiretroviral therapy both can have negative effects on arteries

utch researchers have found associations between HIV infection and unfavourable changes in the arteries, contributing to the ongoing effort to understand why some people with HIV appear to be at elevated risk for cardiovascular problems. Their cross-sectional study, reported in the February 1st edition of the Journal of Acquired Immune Deficiency Syndromes, measured artery wall thickness and artery stiffness in HIV-positive individuals and in a control group of HIV-negative people. HIV infection was independently associated with both of these indicators of cardiovascular risk, and there was also an association between antiretroviral therapy (ART) use and artery stiffness.

Offline John2038

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« Reply #235 on: January 29, 2009, 01:08:04 PM »
so the research at the "city of hope medical centre" is to eradicate the virus or curb it and prevent  aids ? - see how can one word change the whole meaning of a certian study !

The scientists are planning further research to establish whether the treatment might rid patients of HIV infection altogether

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« Reply #236 on: January 30, 2009, 09:07:29 AM »
Abbott Drug Pricing Condemned By AIDS Advocates In International Protests

As part of an ongoing multinational campaign to lower drug prices and improve access to lifesaving AIDS treatments globally, AIDS advocates from three countries-Colombia, Mexico and the United States-are holding simultaneous protests today in each of the three countries targeting Chicago-based pharmaceutical giant Abbott Laboratories over the pricing of its AIDS drug, Kaletra, which can be a key component of lifesaving AIDS drug treatment regimens, particularly as part of what are known as 'second-line' treatments and salvage therapy.

Advocates from AIDS Healthcare Foundation (AHF), the group coordinating the US protest in the Chicago area (which is being supported by local student activists who have been involved in the AIDS drug pricing issue) will also release a sixty second video parody lambasting Abbott and its CEO, Miles D. White over the drug giant's continuing coldhearted actions on the pricing of its key AIDS drugs. The video parody will premiere publicly for the first time when it is posted on YouTube Wednesday in conjunction with the coordinated international protests in the three countries. The spot will then also run as a paid television commercial on select Chicago area television stations.

Link to a preview of the video parody: http://www.youtube.com/watch?v=6cJXSKIDcNU

Abbott Protest Schedules/Locations-US

UNITED STATES-Chicago

WHAT: Protest re: Abbott's AIDS Drug Pricing of Kaletra

WHEN: Wednesday, Jan 28, 2009 at 10:00 a.m.

WHERE: in front of the home of
Abbott CEO Miles D. White
1313 North Green Bay Road
Lake Forest IL 60045

VISUALS: 3ft x 5ft "Shame on Abbott" placards & banners; also, release of TV commercial/video parody of Abbott and its CEO Miles White

POST-PROTEST Press Conference & Teleconference Call- CHICAGO


What: Follow Up POST-PROTEST Press Teleconference Call-
Multinational Protests re: Abbott Laboratories' AIDS Drug Pricing, Release of Parody Video

Where: Hotel Allegro, Cinema Room #1 (3rd Floor) 171 W Randolph St, Chicago IL 60601

When: 1:00 PM (Central & Mexico Time, 2:00 pm Colombia time)-Wednesday, January 28th

How: Teleconference Dial in information

US Callers
+1.877.411.9748 participant code #7931503

International Toll Callers
+.1.636.651.3128 participant code #7931503

Source


A bad start on AIDS

President Obama is all about sound science and a fresh global image. On these points he has no better opportunity than building on the prior White House's $15 billion worldwide AIDS program, one of former
President George W. Bush's notable successes.

But he fumbled the first step with summary firing of Dr. Mark Dybul, who was dismissed as global AIDS czar the day after Obama's swearing-in. It was unexpected, unceremonious and undeserved.

It's a president's prerogative to name his own team, and the Obama insiders and Dybul had agreed on a waiting period before a successor was lined up. But that orderly timetable was shredded after politics entered the picture.

Dybul, a gay physician who once worked in San Francisco, was scapegoated for the marginal portions of the Bush AIDS initiative such as an emphasis on sexual abstinence and a ban on aiding prostitutes. These stances, while objectionable, never stood at the heart of far-larger goals of prevention, research and medical treatment that has enrolled two million worldwide. But to critics, Dybul didn't object loudly enough and had to go, pronto, this instant, right now.

These are intemperate charges that miss the big picture: a conservative White House that woke up to a global scourge and actually did something. In noting Dybul's departure, the British public health journal Lancet described the effort as "the largest and most successful bilateral HIV/AIDS programme worldwide."

If the president isn't careful, the AIDS fight may return to the bad old days with factions fighting over the latest trend or more perfect answer. It's a special worry as Congress is asked to follow through on its vote last year to increase spending to $48 billion in future years, a pledge that looks iffy as economic conditions tighten.

Obama should mend his mistake by finding a replacement who matches Dybul's experience and competence. That task could be a challenge given shabby handling of this praiseworthy public official.

Source

Offline John2038

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« Reply #237 on: January 30, 2009, 03:22:46 PM »
HIV Mutations Can Both Reduce and Enhance Virological Response to Boosted Darunavir (Prezista)

Development of viral resistance to anti-HIV drugs is a potential barrier to long-term treatment success. In the current study, published ahead of print in the January 15, 2009 online edition of the Journal of Antimicrobial Chemotherapy, French researchers sought to identify a pattern of HIV protease gene mutations associated with virological response to regimens containing ritonavir-boosted darunavir (Prezista).



The investigators analyzed 153 treatment-experienced patients starting a new salvage regimen that included darunavir/ritonavir as the sole protease inhibitor (PI). At baseline, median HIV RNA level was 4.7 log10 copies/mL and the median CD4 cell count was 142 cells/mm3.

Virological response was defined as an HIV RNA load < 200 copies/mL at month 3. The impact of individual protease gene mutations on virological response to darunavir/ritonavir was evaluated, and the combination of mutations most strongly associated with response was identified.

Results

    * At month 3, 55% of patients had a virological response and the median decrease in viral load
     from baseline was 1.7 log10 copies/mL.
    
    * All patients had detectable plasma darunavir concentrations at month 3.

    * Cochran-Armitage procedure identified 8 mutations with a negative impact on virological response,
      namely K14R, K20I, E34Q, I47V, I54M, K55R, T74P, and I84V.

    * 2 mutations (E35D and V82A), by contrast, had a positive impact on virological response.

    * In multivariate analyses, genotypic resistance scores were highly predictive of virological
      response at month 3.

    * Other predictors were baseline plasma viral load and use of enfuvirtide (Fuzeon) in
      enfuvirtide-naive patients.

The study authors wrote, "Among the eight mutations with a negative impact on the virological response, I47V, I54M, T74P and I84V were previously described as darunavir resistance-associated mutations." The others were newly identified.

They also observed that some PI resistance mutations had a positive impact on virological response, indicating that they rendered HIV more susceptible to darunavir/ritonavir.

In conclusion, the researchers stated, "These findings might help to explain the potency of darunavir/ritonavir on PI-resistant HIV."

Source


Changes in Darunavir/r Resistance Score After Previous Failure to Tipranavir/r in HIV-1-Infected Multidrug-Resistant Patients

Objectives: To evaluate changes in resistance to tipranavir/r (TPV/r) and darunavir/r (DRV/r) in patients who had failed a TPV/r-including regimen.

Methods: HIV genotypes obtained both at baseline and at tipranavir/r failure (TPVF) were analyzed in 47 HIV-infected patients failing a TPV/r-including regimen. Genotypes were evaluated through the Stanford mutation score: patients were ranked for TPV/r and DRV/r resistance as susceptible (class 1), potential low-level (class 2), low-level (class 3), intermediate-level (class 4), and high-level resistance (class 5). Values are expressed as median (interquartile range) or as frequency (%).

Results: Forty-seven patients were eligible. At baseline (tipranavir initiation), the scoring for TPV/r was: class 3 = 4 (8.5%); class 4 = 31 (66%); and class 5 = 12 (25.5%). Corresponding scores for DRV/r were: class 2 = 1 (2%), class 3 = 12 (25.5%), class 4 = 32 (68%), and class 5 = 2 (4.5%). At TPVF, a shift toward a higher TPV/r scoring class was seen in 16 (34.1%) patients (P = 0.001), whereas a shift toward a higher DRV/r scoring class was observed in 9 (19.2%) patients (P = 0.2381). After TPVF, 25/47 patients (53%) were treated with a DRV/r-containing regimen. After 24 weeks (on-treatment analysis), the median HIV RNA decrease was 3.04 (2.13-3.45) log10 copies per milliliter in DRV/r group versus -0.04 (-0.44; 0.50) log10 copies per milliliter in patients not treated with a DRV/r-containing regimen (P < 0.0001); CD4+ increase was 126 (70-169) cells per cubic millimeter in DRV/r group versus -42 (-121; 42) (P < 0.0001).

Discussion: Treatment with TPV/r did not significantly increase the resistance score to DRV/r and did not preclude the efficacy of subsequent treatment with DRV/r.

Source


Reduction in circulating markers of endothelial dysfunction in HIV-infected patients during antiretroviral therapy

Antiretroviral therapy (ART) in HIV-infected patients is associated with increased cardiovascular risk. Circulating markers of endothelial dysfunction may be used to study early atherogenesis. The aim of our study was to investigate changes in such markers during initiation of ART. Methods

In 115 HIV-positive treatment-naïve patients, plasma lipids, E-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), tissue-type plasminogen activator inhibitor 1 (tPAI-1) and high-sensitivity C-reactive protein (hsCRP) were measured before and after 2 and 14 months of ART. A control group of 30 healthy subjects was included. Values are mean±standard error of the mean. Results

Prior to treatment, HIV-infected patients had elevated levels of sICAM-1 (296±24 vs. 144±12?ng/mL), tPAI-1 (18?473±1399 vs. 5490±576?pg/mL) and hsCRP (28?060±5530 vs. 6665±2063?ng/mL) compared with controls (P<0.001). In contrast, sVCAM-1 and E-selectin did not differ between the groups. Initiation of ART resulted in significantly lower levels of E-selectin (15.1±0.8; P<0.01), sICAM-1 (248±12?ng/mL; P<0.05), sVCAM-1 (766±33?ng/mL; P<0.001) and hsCRP (14?708±2358?ng/mL; P<0.001) after 2 months, which remained reduced at 14 months. tPAI-1 was not influenced by initiation of ART. Conclusions

Markers of endothelial dysfunction were elevated in treatment-naïve HIV-infected patients and were related to HIV RNA viral load. Initiation of ART reduced the levels of the majority of these markers. The positive effect of ART initiation was dependent on the duration of HIV infection prior to treatment.

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Offline John2038

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« Reply #238 on: February 02, 2009, 11:00:37 AM »
Aidsmap

Internet dating does not increase STI risk
Finding sex through the internet does not increase the risk of catching the two most common sexually transmitted infections, a US survey published in Sexually Transmitted Infections has found. Indeed in the case of heterosexual men, meeting partners through the internet was associated with a lower risk of sexually transmitted infections compared with other ways of meeting.

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Repeated exposure to HIV during oral sex elicits HIV-neutralising antibodies in HIV-negative men
Some HIV-negative men in long term relationships with HIV-positive men have an antibody response in saliva which may inhibit HIV infection, report Swedish researchers in an article published online ahead of print in AIDS. This is the first time that such a response has been described in saliva, and may help explain why infection through oral sex is somewhat infrequently reported even in serodiscordant couples.

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Cancer is an increasingly important cause of death in people with HIV
Over a third of deaths in HIV-positive patients in France in 2005 were caused by cancers, investigators report in a study to be published in the March 1st edition of Clinical Infectious Diseases (now online). This represents a significant increase in the proportion of cancer-related deaths in amongst French HIV-positive patients since 2000.

The investigators suggest that better cancer prevention, monitoring and care could help reduce the amount of death caused by malignancies in patients with HIV, and also stress the importance of keeping the CD4 cell count of HIV-positive individuals above 250 cells/mm3.

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Hivandhepatitis

Smoked Medical Cannabis Relieves Neuropathy Pain in HIV Patients
Painful peripheral neuropathy, a side effect of certain antiretroviral drugs, contributes to reduced quality of life and impaired daily functioning for many HIV positive individuals. Opiates and related drugs may be used to manage neuropathy pain, but these medications can cause their own side effects and carry the potential for dependence.

Medicinal cannabis has also been studied for relief of neuropathy pain in people with HIV, and research indicates that cannabinoid receptors in the central and peripheral nervous systems modulate pain perception.

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Treatment Interruption Is Safe and May Modestly Improve Metabolic Parameters in Patients with Well-preserved Immune Function
Evidence has accumulated in recent years -- including extensive data from the large SMART trial, -- demonstrating that CD4-guided antiretroviral treatment interruption is a potentially risky strategy.

But some studies suggest that patients who started treatment "too soon" according to treatment guidelines may be able to safely discontinue therapy.

As described in the December 1, 2008 Journal of Acquired Immune Deficiency Syndromes, Daniel Skiest and colleagues assessed quality of life (QOL), symptoms, blood lipid levels, and body measurements in patients who underwent prolonged treatment interruption (up to 96 weeks) in the ACTG 5170 study.

Avoidance of drug-related toxicities is often cited as a reason for interrupting antiretroviral therapy (ART), but the researchers noted that the consequences of treatment interruption on QOL, body habitus, and metabolic parameters have not been well studied.

This prospective trial included 167 participants with a pre-treatment and current CD4 count > 350 cells/mm3 (the threshold for treatment initiation in the current U.S. and European guidelines), HIV RNA < 55,000 copies/mL at study entry, and use of ART for at least 6 months.

At baseline, the median CD4 count was 833 cells/mm3, the median nadir (lowest-ever) CD4 count was 436 cells/mm3, and the median time on ART was 4.5 years. Most patients (n = 149) were receiving a thymidine analog NRTI -- that is, zidovudine (AZT; Retrovir) or stavudine (d4T; Zerit) -- before treatment interruption; these drugs have been associated with metabolic abnormalities and fat loss (lipoatrophy).

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Longer Exposure to NRTIs, especially Stavudine (Zerit), Increases the Risk of Insulin Resistance in Women with HIV
This prospective study included 1614 HIV positive and 604 HIV negative at-risk participants in the Women's Interagency HIV Study (WIHS) followed between October 2000 and March 2007. Insulin resistance, estimated using the homeostasis model assessment (HOMA-IR) method, was evaluated during a total of 11,019 semiannual visits.

Results

   * HIV positive women reporting HAART use had a higher median HOMA-IR score than HIV
      negative women:
        o 1.20 times higher for those using protease inhibitors (PIs);
        o 1.10 times higher for those using PI-sparing HAART.
    * Among the HIV positive women, cumulative exposure to nucleoside/nucleotide reverse
       transcriptase inhibitors (NRTIs) for > 3 years was associated with a median HOMA-IR score 1.13
       times higher that of women with no NRTI exposure.

    * Cumulative exposure to the NRTI stavudine (d4T; Zerit) for > 1 year was associated with a
       HOMA-IR score 1.15 times higher than that of women who never used this drug.

    * Other factors associated with a higher HOMA-IR score were family history of diabetes, hepatitis C
       virus (HCV) seropositivity, higher body mass index, and menopause.
   
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EATAG

Genital inflammation linked to multiple-variant HIV infections
New HIV-1 infections are more likely to involve multiple viral strains when a patient already has a genital infection, researchers here said.

Most patients with new HIV infections show only a single genetic variant of the virus, reported Eric Hunter, Ph.D., of Emory University, online in the open-access Public Library of Science Pathogens.

But among 42 newly infected individuals included in the study, five had multiple genetic variants of the virus -- and all five had inflammation or ulceration of the genitals, the researchers found.

The findings suggest that the genital mucosal barrier is responsible for what has been termed the "severe genetic bottleneck" for HIV during the infection process.

Earlier studies by Dr. Hunter and other research groups had indicated that, in most cases, only a single HIV variant can establish infection even though the exposure may include several different strains.

Dr. Hunter and colleagues said the current study shows that when the barrier is disrupted by a sexually transmitted disease, this bottleneck may be removed and multiple HIV strains can take hold simultaneously.

The exact nature of the bottleneck remains uncertain, they said.

But the processes by which HIV crosses the genital mucosa to establish infection are among the most promising targets for preventive interventions, Dr. Hunter and colleagues said.

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Offline John2038

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Re: John2038's Research News
« Reply #239 on: February 03, 2009, 10:35:30 AM »
NATAP

High Frequency of Vitamin D Deficiency in Ambulatory HIV-Positive Patients

"As expected, low vitamin D intake was associated with severe 25-D deficiency. We also found a high frequency of secondary hyperparathyroidism, possibly from vitamin D deficiency. One unexpected finding was a possible association between concurrent antiretroviral use and elevated PTH levels."
 
"Subclinical vitamin D deficiency is common in the general population and has been shown to correlate with osteoporosis"..... "A high prevalence of 25-D deficiency has been reported in some HIV-infected cohorts.......in patients with HIV-associated lipodystrophy in the southeastern United States (92%)"..... The optimal 25-D concentration in serum is controversial . The current normal value for serum concentration is 20 ng/ml..... "Lower vitamin D intake was significantly associated with severe (< /=10 ng=ml) 25-D deficiency ( p=0.01) and tended to be associated with moderate 25-D deficiency ( p=0.08, both Wilcoxon rank-sum test). There was a suggestion that lower vitamin D intake (<250 IU) and lack of regular exercise were associated with moderate 25-D deficiency (OR 3.3; 95% CI 1.0, 10.3, p=0.05 and OR 3.1; 95% CI 0.9, 11.1, p=0.09, respectively)."....... "Elevated PTH serum levels (>60 pg=ml) were significantly associated with concurrent antiretroviral use ( p=0.01); of the subjects who were not taking antiretrovirals, none had elevated PTH levels, whereas 40% of those on antiretrovirals had elevated PTH. Elevated PTH levels were also significantly associated with low daily calcium intake (<1000 mg) (p=0.03) and tended to be associated with low daily vitamin D intake (<250 IU) (p=0.07, both Wilcoxon rank-sum test)."....... "All of our subjects were normocalcemic; however, low-normal serum calcium (8.5-8.9 vs. >/=9mg/dl) was associated with increased PTH levels (OR=13.85, CI 1.48, 129.9, p=0.0116). Similar to other reports, PTH levels were negatively correlated with 25-D levels (r= -0.48; p=0.0003).21,23"
 
"Serum 25-D levels of >32 ng/ml may be needed to maintain normal calcium absorption and PTH levels.37,42 As higher PTH levels tend to be seen only in individuals with low 25-D vitamin levels and low daily calcium intake (<800mg/day),23 a daily vitamin D intake of at least 700-800 IU taken with 1200-1500mg of calcium may be necessary for bone health.24,26,38,39,42"

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Aidsmap

Study supports use of 21 days doxycycline to treat LGV

LGV is an ulcerative, sexually transmitted infection caused by a strain of chlamyida. It spreads beyond the musocal linings causing inflammation and the destruction of tissue.

Dutch investigators have found evidence supporting the recommended 21 days of doxycycline treatment for the sexually transmitted infection lymphogranuloma venereum (LGV).
In an article published the online edition of Clinical Infectious Diseases they report that the genetic material of LGV was still detectable in rectal swabs up to 16 days after treatment for the infection was initiated. However, they find no evidence to support treating LGV for up to 42 days should symptoms of the infection persist, noting such symptoms are likely to be the result of inflammation rather than the persistence of the infection.

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Reuters UK

New AIDS approach disrupts patient's DNA



WASHINGTON (Reuters) - California biotechnology company Sangamo BioSciences Inc. said on Monday it will start human testing of a new approach to treating the AIDS virus that involves deliberately damaging the patient's DNA.

The approach is based on research that has long shown that people with a certain mutation in a gene called CCR5 resist infection with the fatal and incurable virus.

The gene controls a doorway called a receptor in immune system cells. The human immunodeficiency virus uses the CCR5 receptor to latch onto the cells it infects.

Sangamo's drug SB-728-T disrupts CCR5. It is a zinc finger nuclease -- a compound that can slice open molecules.

This one is specifically designed to disrupt CCR5. The company plans to remove immune cells called CD4 T-cells from HIV patients, treat them with the drug and re-infuse them.

The hope is these damaged cells will thrive and multiply and give the patient an immune system resistant to HIV.

"This is the first time that we have had the ability to make a patient's T-cells permanently resistant to infection by CCR5-specific strains of HIV and we are very excited to begin a clinical trial of this novel zinc finger nuclease-based therapy," said Dr. Carl June of the University of Pennsylvania School of Medicine, who will help test patients.

The company said its phase I study is meant to look for safety only, and 12 patients with advanced HIV infection will be recruited.

"The ability to protect immune cells from infection with HIV and the expansion of CCR5-modified T-cells has the potential to provide long-term control of both the virus itself and eventually the opportunistic infections characteristic of AIDS," June said.

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Offline John2038

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Re: John2038's Research News
« Reply #240 on: February 03, 2009, 10:39:29 AM »
Blog

Trial Begins for HIV Gene Therapy

Gene therapy that could immunize people against the most common type of HIV is ready to be tested on humans.

The first people to receive the experimental treatment will be HIV patients with drug resistance problems.

"We do have good treatments for HIV. That has been one of the most successful stories of the last 20 years in Medicine," said Pablo Tebas, an infectious disease expert at the University of Pennsylvania.

"However, over time, if the medications are not taken properly, individuals develop resistance to the HIV treatments, so they tend to have more limited therapeutic options."

Since the discovery that a small portion of people who are exposed to HIV do not get infected, scientists have been working to discover the secret to those people's resistance and how to make others resistant as well.

It turns out that most people have a gene called CCR5, which makes them vulnerable to HIV infections. The naturally resistant people have mutant CCR5 genes that inhibit HIV.

Previously, scientists found that by cutting the CCR5 gene out of white blood cells involved in the immune response known as T-cells, they could protect a tube full of human cells from the virus. The gene editing technique relies on proteins called zinc finger nucleases that can delete any gene from a living cell.

In theory, zinc finger nucleases could give that immunity to anyone.

The procedure is simple: Take some healthy T-cells out of an HIV patient, clip out their CCR5 genes, grow more of these clipped T-cells in a dish, and then put them back in the patient.

"In this first study we will re-infuse approximately 10 billion of these cells back into the participants, and we will see if it is safe and if those cells inhibit HIV replication in vivo," said Tebas. "We know they do in the test tube."

See Also:

    * Gene Editing Could Make Anyone Immune to AIDS
    * Biotech Company Gives GMO Crops the Finger
    * Researchers Copyleft a Better DNA Scissor
    * Top 10 Scientific Breakthroughs of 2008

Offline sensual1973

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Re: John2038's Research News
« Reply #241 on: February 03, 2009, 10:52:39 AM »
and where is that taking place?,any direct link where we can get updates about this study ?

tanx John
God grant me the serenity to accept the things i can not change.

Offline John2038

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Re: John2038's Research News
« Reply #242 on: February 03, 2009, 01:07:04 PM »
sensual1973

This trial is still not listed here, but you can contact either:

Thomas Kenney

General Information
502 Johnson Pavilion 
Philadelphia ,PA 19104
thomas.kenney@uphs.upenn.edu
Tel: 215-349-8092
Fax: 215-349-8011
   
Or

Pablo Tebas, M.D.
AIDS Clinical Trial Unit
8 Penn Tower
34th & Civic Center Blvd.
Philadelphia, PA 19104-4283
pablo.tebas@uphs.upenn.edu
(215) 349-8092

John
« Last Edit: February 03, 2009, 01:09:19 PM by John2038 »

Offline John2038

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Re: John2038's Research News
« Reply #243 on: February 05, 2009, 04:51:11 AM »
Medicalnewstoday

Once-Daily Prezista(R) (Darunavir) For Treatment-Naïve Adults With HIV-1 Receives EU Approval As Part Of Combination Therapy
Tibotec Pharmaceuticals announced that the European Commission approved once-daily dosing of 800 mg PREZISTA® (darunavir), a protease inhibitor, with low-dose ritonavir as part of combination therapy in treatment-naïve adults (those who have never taken HIV medication before). This approval broadens the previous indication of darunavir for treatment-experienced HIV-1 patients. Darunavir was developed by Tibotec Pharmaceuticals and is marketed in Europe by Tibotec, a division of Janssen-Cilag.

"We welcome PREZISTA's availability as an effective, once-daily option for adults who have never taken HIV medication before. It has made a significant contribution in the care of treatment-experienced adults with HIV for the last two years, and this is an important treatment development for patients," said Mark Nelson, M.D., Consultant Physician and Deputy Director of HIV Research at Chelsea and Westminster Hospital, London, United Kingdom.

The approval is based on 48-week analyses of plasma HIV RNA levels and CD4+ cell counts from ARTEMIS, an open-label phase III trial in antiretroviral treatment-naïve HIV-1-infected adults. ARTEMIS studied the efficacy and safety of darunavir/r vs. lopinavir/r in combination with other antiretrovirals. The data showed that darunavir was non-inferior to the comparator, although more patients in the darunavir/r arm achieved undetectable viral load (less than 50 copies/mL) compared to lopinavir/r (84 percent vs. 78 percent). The common adverse drug reactions (ADRs) reported of at least moderate intensity (=Grade 2) in the darunavir/r arm were hypertriglyceridaemia, hypercholesterolaemia, headache, diarrhoea, nausea, and increased alanine aminotransferase.

Darunavir 400 mg, co-administered with low dose ritonavir is indicated in combination with other antiretroviral (ARV) medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection in antiretroviral therapy (ART) naïve adults.

Darunavir was given conditional marketing authorisation by the European Commission in February 2007, and received full marketing authorisation in December 2008.

"We strive to provide innovative treatment options for people living with HIV," said Roger Pomerantz, M.D., President of Tibotec Research and Development. "We are proud to make darunavir available to those who are just starting HIV treatment for the first time."

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esciencenews

Green tea may negate the effects of a common cancer therapy
Green tea products have become regarded as a valuable health supplement, as studies have shown evidence of its benefit against a variety of diseases, including cancer. However, a new study suggests that some components of green tea may counteract the anticancer effects of one cancer therapy, bortezomib (Velcade®), and may be contraindicated for patients taking this medicine to ensure its maximum therapeutic benefit. This study is being prepublished online today in Blood, the official journal of the American Society of Hematology. Because of its increasing popularity and availability to the public in many formulations, green tea has been increasingly studied to understand its effect on cancer, heart disease, and other conditions. In animal studies, an antioxidant compound in green tea called the EGCG polyphenol (epigallocatechin gallate) has been shown to be a potent anticancer agent, with effects demonstrated against leukemia, as well as lung, prostate, colon, and breast cancer. Among other properties, EGCG binds to a common protein in tumors called GRP78 (which is responsible for preventing cell death) and inhibits its function, thereby assisting in the death of tumor cells.

“We know that cancer patients look to green tea extracts among other natural supplements to complement their therapeutic regimens. We wanted to better understand how the compounds in green tea interact with a cytotoxic chemical therapy and how that may affect patient outcomes,” said Axel Schönthal, PhD, of the University of Southern California Keck School of Medicine and senior study author.

In this study, researchers evaluated whether the combination of green tea and bortezomib would improve outcomes against multiple myeloma, a blood cancer, and glioblastoma, a malignant brain tumor. Bortezomib, an anticancer therapy approved to treat multiple myeloma and mantle cell lymphoma, normally fights disease by inhibiting proteasomes and inducing tumor cell death. However, in both in vitro and in vivo mouse experiments, the team was surprised to find that the EGCG compound seemed to prevent bortezomib from fighting the disease by blocking its proteasome inhibitory function – the two compounds effectively contradicted one another in the cell, leaving nearly 100 percent of the tumor cells intact.

Importantly, the team found that EGCG only reacted with proteasome inhibitors that have a boronic acid base (including bortezomib) but did not react with several non-boronic acid-based proteasome inhibitors (such as nelfinavir [Viracept®], a treatment for HIV). The researchers determined that the boronic acid in bortezomib helped to bind the EGCG directly to the therapy molecule, thereby cancelling out the effects of both the green tea and the therapy on the tumor cells.

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hivandhepatitis

Once-daily Regimen of Nevirapine (Viramune), Tenofovir (Viread), and Lamivudine (Epivir) Is Associated with Early Virological Failure


The current standard of care for antiretroviral therapy for HIV is a triple-drug regimen consisting of 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor.

Regimens taken once-daily are more convenience and are associated with better adherence than those taken more often. The NNRTI efavirenz (Sustiva) is administered once-daily, but is not appropriate for all patients, due to its neuropsychiatric side effects and risk of birth defects during pregnancy. The other commonly used NNRTI, nevirapine (Viramune) is approved for twice-daily dosing, but researchers have also tested it as a once-daily option.

As described in the February 2009 Journal of Antimicrobial Chemotherapy, French researchers conducted an open-label non-inferiority trial comparing lamivudine (3TC; Epivir) plus tenofovir (Viread) plus nevirapine, all administered once-daily, versus zidovudine (AZT; Retrovir) plus lamivudine plus nevirapine administered twice-daily.

As of May 2006, 71 treatment-naive patients with a CD4 count < 350 cells/mm3 had been enrolled (out of a projected 250) and an unplanned interim analysis was performed. The groups were comparable at baseline, with a median CD4 count of about 195 cells/mm3 and a median plasma viral load of about 5 log10.

Results

    * 8 patients experienced early non-response in the once-daily group (22.2%), while all patients
       responded in the twice-daily group.

    * There were also 2 cases of later viral rebound in the once-daily group.

    * Resistance genotypes for the 9 failing patients in the once-daily group showed that all had the
       mutations M184V/I (n = 3), K65R (n = 6), and 1 or more NNRTI resistance mutations.

    * At baseline, the 9 patients in this group who experienced treatment failure had a higher median
       plasma viral load and a lower median CD4 count than other participants in the group (5.4 vs 4.7
       log10, P = 0.002; 110 vs 223 cells/mm3, P = 0.004).

    * Nevirapine trough concentrations did not differ significantly between the 2 groups, nor between
       patients with full viral suppression and those who experienced treatment failure in the once-daily
       group.

Based on these findings, the study authors concluded, "In antiretroviral-naive HIV-1-infected patients, the once-daily lamivudine, [tenofovir] and nevirapine regimen resulted in a high rate of early virological failures."

However, they added, "The reasons for the failures remain unclear."

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Benefits versus Risks of Stavudine (Zerit) Therapy for HIV-related Neurological Complications
A recent report found that the frequency of HIV-associated cognitive impairment or dementia at the Infectious Disease Institute in Kampala, Uganda, was 31%. Co-formulated generic medications including the NRTI stavudine (d4T; Zerit) are commonly used to treat HIV patients in Uganda and in many other parts of Africa, though stavudine is no longer considered a preferred option in wealthy countries due to its side effects.

The aim of the current study, published in the January 13, 2009 issue of Neurology, was to evaluate the benefits and risks of stavudine-based HAART for HIV-related cognitive impairment and distal sensory neuropathy.

The study compared neuropsychological performance changes in HIV positive patients initiating HAART for 6 months and HIV negative individuals receiving no treatment for 6 months. The researchers also evaluated the risk of antiretroviral-associated toxic neuropathy resulting from use of stavudine.

At baseline, 102 HIV positive individuals in Uganda received neurological, neuropsychological, and functional assessments. They then began HAART and were followed for 6 months. In addition, 25 HIV negative individuals received the same clinical assessments and were also followed for 6 months.

Results

    * In the HIV positive individuals, there was improvement in verbal memory, motor and psychomotor
       speed, executive thinking, and verbal fluency after starting HAART.

    * Symptoms of neuropathy developed in 38% of previously asymptomatic HIV positive patients after
       initiation of a stavudine-based regimen.

In conclusion, the study authors wrote, "After the initiation of HAART, including stavudine, HIV positive individuals with cognitive impairment improve significantly as demonstrated by improved performance on a test of executive function."

However, they noted, "peripheral neurotoxicity occurred in 30 patients, presumably because of stavudine-based HAART, suggesting the need for less toxic therapy."

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Mindfulness Meditation May Help Slow Immune System Decline in People with HIV


Results

    * Participants in the 1-day control seminar showed declines in their CD4 counts, while those in the
       8-week MBSR program had stable CD4 counts from baseline through the post-intervention
       measurement (P = 0.02).

    * This effect on CD4 cells was independent of antiretroviral therapy.

    * Additional analyses indicated that good adherence to the mindfulness meditation program, as
       measured by class attendance, was associated with greater CD4 cell preservation.

    * Participants in the MBSR program also reported greater improvement in their quality of life.

In conclusion, the study authors wrote, "These findings provide an initial indication that mindfulness meditation training can buffer CD4+ T lymphocyte declines in HIV-1 infected adults."

"The mindfulness program is a group-based and low-cost treatment," lead author David Creswell said in a press release issued by UCLA. "If this initial finding is replicated in larger samples, it's possible that such training can be used as a powerful complementary treatment for HIV disease, alongside medications."

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European Association for the Study of the Liver (EASL) Published Updated Guidelines for Management of Chronic Hepatitis B
Several new antiviral agents have been evaluated and licensed since the previous EASL consensus conference in 2002. Currently 7 hepatitis B therapies are approved in Europe: conventional interferon alpha, pegylated interferon alpha, lamivudine (Epivir-HBV), telbivudine (Tyzeka or Sebivo), entecavir (Baraclude), adefovir (Hepsera), and tenofovir (Viread).

Low baseline HBV DNA and elevated ALT predict good response to interferon or nucleoside/nucleotide drugs, but HBV genotype only seems to make a difference with regard to interferon response, with genotypes A and B being associated with better response than C and D.

Development of drug resistance is a major barrier to long-term treatment success, and the guidelines include a discussion of treatment strategies, including combination versus sequential therapy and short-term versus continuous treatment.

The document includes guidance for management of patients with compensated and decompensated cirrhosis, as well as liver transplant recipients. Management of children and pregnant women with hepatitis B is also discussed.

There are also sections on dealing with patients with HIV-HBV coinfection and HBV-HCV coinfection. Indications for treatment are the same in HIV positive and HIV negative individuals, based on HBV DNA level, serum ALT, and extent of liver damage. In agreement with current HIV treatment guidelines, the EASL panel recommended that coinfected patients should be simultaneously treated for both HIV and HBV using the dually active agents tenofovir and emtricitabine (Emtriva) plus a third agent active against HIV. For the small number of patients who must be treated for HBV before HIV, the authors added, adefovir and telbivudine -- which are not proven to be active against HIV -- should be preferred. In contrast, lamivudine, entecavir, and tenofovir are contraindicated as single agents for hepatitis B in coinfected patients.

Finally, the authors concluded with a section on unresolved questions and unmet needs that could be addressed in future research, including improved knowledge of the natural history of chronic hepatitis B, indirect markers of liver disease severity, the role of HBV genotype in determining disease prognosis, optimal duration of treatment, efficacy of various combination regimens, and development of new agents for multidrug-resistant HBV.

"Several difficulties remain in formulating treatments for chronic hepatitis B, thus areas of uncertainty exist," the EASL panel wrote. "At the present time clinicians, patients and public health authorities must continue to make choices on the basis of evidence that is not fully matured."

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Extended Pegylated Interferon plus Ribavirin Therapy Improves Sustained Response Rate in Slow Responder Genotype 1b Hepatitis C Patients
A considerable proportion of chronic hepatitis C patients do not achieve sustained virological response (SVR) to standard therapy with pegylated interferon plus ribavirin for 24 weeks (for HCV genotypes 2 or 3) or 48 weeks (for genotypes 1 or 4), leading researchers to study the benefits of longer treatment. While some studies have seen good outcomes with 72 weeks of therapy, the optimal duration is unknown

In a study reported in the January 2009 American Journal of Gastroenterolgy, 113 hard-to-treat genotype 1b patients with high pre-treatment HCV viral load were randomly assigned to receive pegylated interferon plus ribavirin for the standard 48-week duration or for an extended duration. In the extended duration group, treatment continued for 44 weeks after patients became HCV RNA negative, for a total duration of 48 to 68 weeks.

Results

    * The SVR rate was 36% (20 of 56) in the standard duration group compared with 53% (30 of 57)
       in the extended duration group -- a difference that did not reach statistical significance (P = 0.07).

    * However, patients in the extended duration group who became HCV RNA negative between
       weeks 16 and 24 had a significantly higher SVR rate than patients in the standard duration group
       (78% [7 of 9] vs 9% [1 of 11]; P = 0.005).

    * The predictive factors for SVR were longer treatment duration and time to undetectable HCV RNA.

Based on these findings, the study authors concluded, "The extended treatment significantly increased the SVR rate in patients who were HCV RNA negative at 16-24 weeks."

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Clinical Update -- Debio 025 in Hepatitis C -- Debiopharm Starts Phase IIb Triple Therapy Study, a Promising Therapeutic Avenue
Lausanne, Switzerland -- January 26, 2009 -- Debiopharm Group (Debiopharm), a global biopharmaceutical development specialist that focuses on serious medical conditions and particularly oncology, announced today the randomization of its first patient in a phase IIb clinical study with Debio 025, a selective cyclophilin (Cyp) inhibitor with a potent anti-hepatitis C (HCV) effect. This multinational, double-blind, placebo-controlled, parallel-group study will investigate the efficacy and safety of three different treatment regimens combining Debio 025 with Peg interferon alpha 2a (peg-IFN alpha-2a [Pegasys]) and ribavirin in treatment-naive chronic HCV genotype 1 patients.

During this 72 week trial, on top of the Standard of Care (SOC) treatment consisting of peg-IFN alpha-2a 180 mcg once weekly and ribavirin 1000 or 1200 mg/day, patients will receive an oral dose of 600 mg of Debio 025. Three different triple combination regimens will be compared to the SOC treatment. The company aims to evaluate whether there is an increase in the proportion of patients who achieve a sustained viral response (HCV RNA < 10 U/mL 24 weeks after treatment end) with Debio 025, compared to the SOC treatment. The trial will include 272 treatment-naive chronic HCV genotype 1 patients. Results of the study are expected in Q1 2011.

"We believe that the future of chronic HCV treatment lies in the combination of drugs with different mechanisms of action and potential additive or synergistic antiviral effects. For this reason we are investigating the use of Debio 025 combined with the current peg-IFN alpha-2a/ribavirin dual therapy. We are optimistic that this combination will reduce the risk of treatment failure for HCV patients and maximise their chances of sustained viral response," said Rolland-Yves Mauvernay, President and Founder of Debiopharm Group.

"With over 170 million people infected with HCV worldwide, there is a real medical need for a treatment which we hope to address," added Kamel Besseghir, CEO of Debiopharm S.A.

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Offline John2038

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Re: John2038's Research News
« Reply #244 on: February 05, 2009, 04:55:13 AM »
sciencedaily

How Much Is The World Spending On Neglected Disease Research And Development ?
The first comprehensive survey of global spending on neglected disease R&D, published in the journal PLoS Medicine, finds that just over $US 2.5 billion was invested into R&D of new products in 2007, with three diseases—HIV/AIDS, TB, and malaria—receiving nearly 80% of the total.

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glaucomatoday

HIV and Ophthalmology: Although advances in medical therapy have reduced the number of lives lost to AIDS and the incidence of associated blinding infections, more subtle ocular manifestations are not uncommon.
A desire to learn more about the ocular manifestations of AIDS and to understand the pathogenesis underlying this newly recognized syndrome led to a fruitful collaboration between Dr. Holland, the late Robert Foos, MD (an ocular pathologist from UCLA), and Dr. Pepose, who had just completed an MD/PhD in virology in immunology at UCLA.3,4

Their initial studies defined the gamut of associated ocular infections, neoplasms, and vascular changes; explored the etiology of cotton-wool spots; and investigated the interaction of concurrent retinal infections with CMV, herpes simplex virus, and human immunodeficiency virus (HIV). They also studied the effects of antiviral therapy on CMV retinitis and the impact of the AIDS epidemic on corneal transplantation.

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upi

$100M given for AIDS vaccine research
BOSTON, Feb. 5 (UPI) -- A Massachusetts couple is donating $100 million to help find an effective vaccine against AIDS.

The presidents of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University said the new Phillip T. and Susan M. Ragon Institute "will bring scientists and clinicians together with engineers using the latest technologies in an interdisciplinary effort to better understand how the body fights infections and ultimately to apply that understanding against a wide range of infectious diseases and cancers."

"This institute will let top researchers from some of the best institutions in the world apply their full creative potential to problems of tremendous global importance." Dr. Bruce Walker, director of the Ragon Institute, said Tuesday in a news release.

Phillip Terrence Ragon, 59, is the founder and sole owner of InterSystems, which provides database software to hospitals and other industries, The Boston Globe said.

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Jaids

Effect of Simultaneous Use of Highly Active Antiretroviral Therapy on Survival of HIV Patients With Tuberculosis
Introduction: The optimal timing for initiation of highly active antiretroviral therapy (HAART) in patients with AIDS and tuberculosis (TB) is an unresolved question. To assess the effect of HAART on the survival of patients with TB, we designed this study.

Methods: We selected all HIV patients included in the COMESEM cohort with TB diagnosis after 1996. Clinical and epidemiological data were registered. We compared patients who started HAART at the diagnosis of TB [simultaneous therapy (ST)] or not. Survival was assessed by Cox analysis.

Results: Among the 6934 HIV patients included in the cohort, 1217 patients had TB, 322 of them (26.5%) after 1996. At the time of TB diagnosis, 45% of them started HAART (ST). There were no differences between groups regarding basal characteristics, except for a lower viral load in ST patients. ST therapy was associated with improved survival (hazard ratio 0.38; 95% confidence interval 0.20 to 0.72, P = 0.003). By univariate analysis, survival was also associated with no endovenous drug use and a later year of TB diagnosis. After adjusting for other prognostic variables, by Cox multivariate analysis, ST remained robustly associated with improved survival (hazard ratio 0.37; 95% confidence interval 0.17 to 0.66, P = 0.001).

Conclusions: Simultaneous HAART and TB treatment in HIV patients with TB is associated with improved survival.

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Offline John2038

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Re: John2038's Research News
« Reply #245 on: February 05, 2009, 04:56:52 AM »
NATAP

High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients
The DAUFIN trial showed an unexpected and high rate of early virological failures in patients treated with tenofovirDF + lamivudine and nevirapine once daily, with a high incidence of resistance mutations to NNRTIs, and K65R conferring broad cross-resistance to nucleoside analogues. At baseline, failing patients had higher viral loads and lower CD4 cell counts than subjects with success. But adherence to treatment was similar in the two groups and we failed to identify any pharmacological explanation for virological failures. Whatever the mechanism that led to the high viral failure rate, we deem it essential to alert that the once-daily combination of tenofovirDF, lamivudine and nevirapine should not be given as a first-line ARV therapy.

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Oral HIV-exposure elicits mucosal HIV-neutralizing antibodies in uninfected men who have sex with men
Of 25 exposed, uninfected individuals (EUI), 21 reported receptive unprotected oral intercourse, whereas three of the 25 reported unprotected anal receptive intercourse. Whole saliva from both EUI and low-risk healthy controls contained HIV-neutralizing activity. However, a significant difference was seen when analyzing the salivary IgA1 fraction: 13 of 25 EUI neutralized HIV, whereas none of the 22 controls had this capacity. The neutralizing capacity of the EUI males persisted during 2 years of follow-up.
 
Conclusion: Unprotected oral sex evokes a salivary IgA1-mediated HIV-neutralizing response that persists over time during continuous exposure in uninfected male partners of infected men

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Oral Cancer In Men Associated With HPV
Patients who have HPV infections are at higher risk for these cancers,'' Dr. Worden said. ''But the good news is that if that's the cause of their cancer, they're more likely to survive treatment. We still don't know what the ideal treatment regimens are. For example, these patients may benefit from less intense chemotherapy and radiation.
 
Although the researchers acknowledge that the number of patients in their study was small, they conclude that especially in patients with HPV-positive tumors, chemotherapy followed by combined chemotherapy and radiation appears to be an effective treatment.
 
An author of the papers has an interest in a company that is developing an HPV detection method.

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Glomerular filtration rates in HIV-infected patients treated with and without tenofovir: a prospective, observational study
Among HIV-infected viraemic persons with modest baseline renal impairment, observed improvements in MDRD that can occur as a consequence of HAART-induced viral suppression may more than offset potential negative effects of tenofovir upon renal function.
 
In conclusion, in our cohort of HIV-infected viraemic persons with modest baseline renal impairment, we observed improvements in MDRD that were likely linked to HAART-induced viral suppression. Specifically, we noted that HIV VL reductions consequent to tenofovir-based HAART usage were associated with GFR improvements. This may imply that the potential negative effects of tenofovir upon renal function were more than offset by tenofovir's beneficial effects upon HIV suppression. Randomized prospective studies are needed to verify these findings.

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New Gene Therapy Disrupts CCR5/HIV Entry: Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
"....HIV-1-infected mice engrafted with ZFN-modified CD4+ T cells had lower viral loads and higher CD4+ T-cell counts than mice engrafted with wild-type CD4+ T cells, consistent with the potential to reconstitute immune function in individuals with HIV/AIDS by maintenance of an HIV-resistant CD4+ T-cell population....
 
"The HIV-infected mice had increased numbers of CD4+ T cells in peripheral blood on days 30 to 50 after infection; however, the early engraftment was not different (Fig. 4f). In addition, mice given CCR5 ZFN-treated cells had substantially lower plasma viremia (mean viral load 8,300 copies/ml) than mice populated with the mock CD4+ T cells (mean viral load 60,100); this demonstrates highly significant protection (P < 0.001, n = 10 mice per group; Fig. 4e). Thus, the modified cells confer resistance to HIV-1 infection in vivo as measured by preferential expansion, viral load and CD4+ T-cell counts. Furthermore, these results demonstrate normal engraftment and growth of these same ZFN-transduced cells even in the absence of this selective pressure"
 
"A limitation of this model is that it is an assay of the resistance to infection, in that it demonstrates that the ZFN-modified CD4+ T cells have been made HIV resistant in vivo, but does not extend to modeling the chronic phase of infection or to issues pertaining to the remaining T-cell repertoire in immunodepleted patients."
 
"In summary, the present results support the clinical development of adoptive immunotherapy in the setting of HIV-1 infection to reconstitute or preserve the memory cell pool of HIV-infected patients with ZFN-modified ex vivo expanded, polyclonal CD4+ T cells that are intrinsically resistant to HIV infection. In our recent preclinical studies we have successfully adapted this process to large scale, yielding 1 times 1010 ZFN-modified CD4+ T cells (data not shown), a number sufficient in principle to support clinical trials. The existence of memory T cells with stem cell-like qualities and the capability for extensive self-renewal40, 41 further supports the rationale for this approach to replenish the memory T-cell pool. Finally, although there would be additional safety considerations in extending this work to stem cells, recent work indicates that it is possible to apply ZFN-based approaches to stem cells42, so that it is conceivable that the framework presented here could be applied to a number of monogenic congenital and acquired diseases."

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« Last Edit: February 05, 2009, 04:59:54 AM by John2038 »

Offline John2038

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Re: John2038's Research News
« Reply #246 on: February 06, 2009, 01:37:47 AM »
NATAP

FDA grants traditional approval of Isentress (raltegravir)
On January 29, 2009, the Food and Drug Administration (FDA) granted traditional approval for Isentress (raltegravir) 400 mg tablets in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients. The product label and patient package insert have been updated to include 48 week data from Studies 018 and 019.

The complete revised label can be found on the FDA web site here

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Patient Information Page from The Hormone Foundation: Vitamin D, Calcium, and Bone Health
Why is bone health important?

Bone is a living tissue that is constantly breaking down and being replaced. Throughout life, your body balances the loss of bone with the creation of new bone. You reach your highest bone mass at about age 30. Thereafter, you begin to lose bone mass.
 
Over time, bone loss can cause osteopenia (low bone mass) and then osteoporosis, a condition in which bones become weak and are more likely to break (fracture). Fractures can cause serious health problems, including disability and premature death. Getting enough vitamin D and calcium is important in keeping your bones healthy and reducing your chances of developing osteopenia or osteoporosis.
 
Why are vitamin D and calcium important to bone health?
 
Vitamin D allows your body to absorb calcium. Calcium is necessary for building strong, healthy bones. Without enough vitamin D and calcium, bones may not form properly in childhood and can lose mass, become weak, and break easily in adulthood. Even if you get enough calcium in your diet, your body will not absorb that calcium if you don't get enough vitamin D.
 
What is vitamin D?
 
Vitamin D is a fat-soluble vitamin, which means it is stored in the body's fatty tissue. People normally get vitamin D through exposure to sunlight, which triggers vitamin D production in the skin.
 
Vitamin D is found naturally in very few foods. In the United States, it is routinely added to milk and infant formula. Other good food sources are egg yolks and some types of fish such as salmon and mackerel. Vitamin D is also available in nutritional supplements.
 
You probably don't get enough vitamin D if you:
 
--spend little time in the sun or use a strong sunblock have very dark skin
--are over age 50, when the body is less able to make and use vitamin D efficiently
--have certain medical conditions such as diseases of the digestive system that interfere with fat and vitamin D absorption
--are very overweight, because vitamin D can get "trapped" in body fat and be less available for the needs of the body
 
What is Calcium?
 
Calcium is a mineral with many functions. Most of the body's calcium is stored in the bones and teeth where it supports their structure. Calcium mainly comes from the foods you eat.
 
Good sources of calcium include dairy products (milk, cheese, yogurt); calcium-fortified products (foods and beverages with added calcium); canned fish with bones; and green, leafy vegetables. Like vitamin D, calcium is also available in supplements.
 
You may need extra calcium if you:
 
--are a post-menopausal woman
--eat few or no dairy products
--have a digestive disease that interferes with nutrient absorption
 
What should you do with this information?
 
Talk with your doctor about your intake of vitamin D and calcium, whether you should take supplements, and how much you should take. In addition to getting enough calcium and vitamin D in your diet, regular, weight-bearing exercise helps keep your bones strong and healthy.



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Tibotec Submits Application to U.S. Food and Drug Administration Seeking Traditional Approval for INTELENCE(TM) (etravirine)
Tibotec, Inc. today announced it has submitted an application to the U.S. Food and Drug Administration (FDA) seeking traditional approval for INTELENCE(TM) (etravirine) tablets, a non-nucleoside reverse transcriptase inhibitor (NNRTI). The application for traditional approval includes 48-week data from two Phase 3 studies known as DUET-1 and DUET-2.

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Aidsmap

HIV treatment during pregnancy does not increase risk of birth abnormalities - even when efavirenz included
HIV treatment during pregnancy does not increase the risk of birth abnormalities, according to the results of a large study published in the online version of AIDS. Researchers from the UK and Ireland looked at the outcome of over 8000 pregnancies in HIV-positive women over a 17 year period and found that the rate of birth abnormalities was the same as that seen in the general population.

Furthermore, no individual anti-HIV drug, including efavirenz (Sustiva, also in the combination pill Atripla) was associated with an increased risk of birth abnormalities. Efavirenz is not recommended for use during pregnancy, especially in the first three months, due to findings from animal studies suggesting a risk of birth defects if the developing foetus is exposed to the drug.

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Untreated HIV depletes CD4 cells in semen - renders men more vulnerable to STIs
HIV infection causes a rapid depletion of immune cells in semen, investigators report in an article published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. This immune depletion could render HIV-positive men more vulnerable to sexually transmitted infections, suggest the researchers, and such infections can increase the risk of onward HIV transmission.

However, the team of US investigators also found that HIV treatment leads to the restoration of immune system cells in semen.

Most cases of HIV have been sexually transmitted. The risk of sexual HIV transmission is affected by a number of factors including the stage of HIV infection, and the presence of an untreated sexually transmitted infection. Both these factors can increase viral load in semen, increasingly the likelihood of HIV transmission.

Previous research has found that soon after infection with HIV there is massive loss of immune system cells in a number of sites in the body, most notably the gut.

However, the effects of HIV, disease stage and HIV treatment on the profile of immune system cells in the male genital tract has not been well described.

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deccanherald

Third AIDS vaccine trial set to commence
AIDS researchers in the country are all set to test a combination of two AIDS vaccines, one of which, when tested individually, did not elicit enough immune response against the dreaded Human Immunodeficiency Virus (HIV). To be conducted in two centres in Pune and Chennai, the new trial is first intended to establish the safety of the combination, comprising of two vaccines – ADVAX and TBC-M4. This will be India’s third AIDS vaccine trial in which a prime-boost strategy – one vaccine to trigger the early immune response which is being flared up by a second shot later – has been adopted.

Thirty two volunteers – 16 each at National AIDS Research Institute, Pune and one at the TB Research Centre, Chennai – will receive two dosages of the ADVAX shot followed by two dosages of the second.

While ADVAX – a DNA vaccine – was designed by the Aaron Diamond Research Centre in New York, TBC-M4 is an AIDS vaccine candidate made by an US firm in collaboration with Indian scientist, Shekhar Chakraborty. When the MVA vaccine was individually tested at TRC in 2006-07, it was concluded that though the vaccine was safe for human use, its immune response was too inadequate to take it to the next stage. This means even if the vaccine is administered, it fails to equip the body with enough weapons to battle the HIV. The alternative strategy is to use MVA with an imported DNA vaccine hoping for a better response.

The new trial – announced by the Indian Council of Medical Research and International AIDS Vaccine Initiative on Thursday – intends to try that out. As the first step, the safety of the combination will have to be established through a phase-I trial.

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hivandhepatitis

Is Dual Therapy with Raltegravir (Isentress) plus a Boosted Protease Inhibitor a Feasible "Rescue" Strategy for Treatment-experienced Patients ?
The present report described a group of 18 patients, out of a cohort of 44 individuals treated with raltegravir as part of a rescue regimen in the Merck 023 Expanded Access Program, who had a boosted PI as the only available active drug to build an OBR.

Out of these 18 individuals, 9 had experienced virological failure with enfuvirtide (T-20; Fuzeon), 5 discontinued it due to injection site reactions, and 4 declined to start it. The novel CCR5 antagonist maraviroc (Selzentry) and the next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (Intelence) were not yet available at the authors' center. In all cases, the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) and NNRTI GSS score was 0.

The physician constructing the patients' salvage regimens decided not to include inactive drugs, so dual-therapy regimens were used. In addition to raltegravir, most patients (n = 13) also received boosted darunavir (Prezista), 1 received lopinavir/ritonavir (Kaletra), 3 received atazanavir (Reyataz), and 1 patient described as "absolutely intolerant" to ritonavir received unboosted atazanavir. While the patients' HIV had numerous protease mutations, both the Stanford and TruGene algorithms showed that they were fully sensitive to the chosen PIs (GSS > 2).

Of the 18 patients starting these salvage regimens, 2 were described as "absolutely non-adherent" to the regimen, and 1 developed acute hepatitis B, discontinued antiretroviral therapy, and did not return to the clinic after recovery. Another patient relapsed into serious depression and stopped all drugs.

Of the remaining 16 patients, 15 rapidly achieved HIV RNA < 50 copies/mL by week 4, and the remaining individual did so at week 8. By week 12, all still had undetectable viral load, and none had interrupted treatment at the time of the report. "Therefore, all adherent patients had undetectable viral load at week 12 (16/16) as [did] all patients who have already reached week 24 (10/10)," the authors wrote. Among the 10 patients who reached week 24, the mean CD4 cell gain was 52 cells/mm3.

No grade 3 or 4 (severe) adverse events or laboratory abnormalities were reported, with the exception of the individual who developed acute hepatitis B. One patient showed a 2-fold increase in ALT and AST at week 12, but this was not confirmed at week 24. In addition, 2 patients showed a grade 2 (moderate) increase in total cholesterol and triglycerides and were successfully treated with rosuvastatin (Crestor).

In conclusion, the authors wrote, "in our cohort where the treatment choice was so narrow, this regimen proved to be potent and highly effective (at least at this short follow-up evaluation), simple, and well accepted by patients."

Taken together, they added, "these observations confirm, as a proof of concept, that the great potency of raltegravir, combined with the potency and high genetic barrier of darunavir, may represent a valuable option in selected patients without chances of building an effective 3-drug regimen. Data on long-term follow-up is though warranted to confirm and extend these results."

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Premature Aging of CD4 Cells May Accelerate HIV Disease Progression
Despite extensive research over the past 3 decades, the mechanisms underlying HIV disease progression are still not fully understood. But a report in the January 7, 2009 Journal of Acquired Immune Deficiency Syndromes adds another piece to the puzzle.

Weiwei Cao and colleagues sought to determine whether untreated HIV infection and disease progression is associated with premature aging of memory CD8 and CD4 T-cells and naive CD4 T-cells. CD4 cells direct the body's immune response. Memory CD4 cells are primed to respond when they encounter a previous invader again, while naive cells are able to respond to new pathogens.

The researchers looked at 20 HIV positive men classified as fast progressors (diagnosed with AIDS within 4 years of infection) and 40 men classified as slow progressors in the Multicenter AIDS Cohort Study.

The expression of cell surface markers on frozen T-cells was measured using flow cytometry, indicating their differentiation stage. Differentiation stage reflects the aging of T-cells. As people age, immune function typically declines. In part, this is related to atrophy of the thymus gland in the neck, where newly produced T-cells mature. In addition, T-cell function decreases over time -- a phenomenon known as "immunosenescence" -- as the cells proliferate in response to antigens. Studies suggest this cellular aging occurs more rapidly in the presence of HIV.

Results

    HIV disease progression was associated with:

        * Decreased CD28 expression (an indicator of immunosenescence) on both CD4 and CD8 T-cells;

        * An increased proportion of intermediate- and late-differentiated CD8 cells;

        * Decreased CD31 expression on naive CD4 cells of recent thymic origin (i.e., recently emerged
           from the thymus).

    Selective depletion of peripherally expanded naive CD4 cells was associated with HIV infection, but not with HIV disease progression.

Based on these findings, the researchers wrote, "The overall change during HIV-1 infection and progression is associated with a shift in the T-cell population toward an aged conformation, which may be further compromised by impaired renewal of the less-differentiated CD4 T-cell population."

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« Last Edit: February 06, 2009, 01:40:43 AM by John2038 »

Offline John2038

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Re: John2038's Research News
« Reply #247 on: February 06, 2009, 01:38:56 AM »
jaids

Carotid Intima-Media Thickness and Arterial Stiffness in HIV-Infected Patients: The Role of HIV, Antiretroviral Therapy, and Lipodystrophy
Objectives: HIV-infected patients using combination antiretroviral therapy (ART) have an increased cardiovascular risk. We aimed to identify the effects of HIV, ART, and lipodystrophy (LD) on carotid artery intima-media thickness (C-IMT), a surrogate measure of atherosclerosis, and arterial stiffness, a marker of cardiovascular risk.

Design: Case-control study of 77 HIV-infected men (55 exposed to ART, 22 ART naive, and 23 with LD) and 52 controls.

Methods: C-IMT was measured ultrasonically, and arterial stiffness was estimated by distensibility (DC) and compliance (CC) coefficients of the carotid, femoral, and brachial arteries, by the carotid Young elastic modulus and pulse wave velocity.

Results: After adjustment for cardiovascular risk factors, HIV-infected patients had a 0.067 mm (10.8%) greater C-IMT than controls, 13.6% and 29.5% lower DC, and 14.1% and 31% lower CC of the carotid and femoral arteries, respectively, but similar Young elastic modulus and pulse wave velocity. Patients exposed to ART had similar C-IMT compared with ART-naive patients but 25.9% lower DC and 21.7% lower CC of the femoral artery. Arterial properties did not differ between patients with and without LD.

Conclusions: HIV infection is independently associated with C-IMT and generally increased arterial stiffness. ART use is associated with increased stiffness of the femoral artery.

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liebertonline

Plasma Lipid Profile in Pregnant Women with HIV Receiving Nevirapine
Limited information is currently available on the metabolic profile of nevirapine in pregnancy. We used data from a national observational study to evaluate plasma lipid profile in pregnant women receiving nevirapine. Lipid values were collected during routine clinical visits. Midpregnancy (second trimester) lipid values were analyzed according to use of nevirapine, calculating differences and 95% confidence intervals (CI) between women taking and not taking this drug. In order to adjust for possible confounders, multivariable models were constructed using as dependent variables levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) levels and TC/HDL-C ratio, and as independent variables age, body weight, previous treatment history, CD4 count, and presence of any antiretroviral therapy, use or nonuse of protease inhibitors, stavudine, and nevirapine at the time of blood sampling. Overall, 375 women had available data for analysis. Pregnant women on nevirapine, compared to women not taking this drug, had in univariate analyses higher levels of HDL-C (difference: +13.0mg/dL [95%CI 7.4–18.6], p<0.001), lower values of TC/HDL-C ratio (difference: -0.51 [0.23–0.80], p<0.001) and a trend for lower levels of triglycerides (difference: -17.6mg/dL [0.7–35.9], p=0.06). Higher HDL-C levels were also associated with use of protease inhibitors and with no previous antiretroviral experience before pregnancy. The associations with higher HDL-C levels were confirmed in multivariable analyses. Our study indicates in pregnant women an association between nevirapine use and higher HDL-C levels. Further studies should assess whether this effect is due to an intrinsic activity of nevirapine and define the potential mechanisms involved.

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Development and Efficacy of an Intervention to Enhance Readiness for Adherence among Adults Who Had Previously Failed HIV Treatment
This paper outlines the development and initial testing of the READY intervention that was designed to enhance readiness for adherence among adults with a history of nonadherence to HIV treatment. Participants in this study were adults (n=28) who ranged in age from 24 to 57: most were male (75%) and African American (64%). Participants had failed an average of four prior HIV treatment regimens due to nonadherence and were beginning a new regimen of protease inhibitor (PI)-based antiretroviral medications. The study was conducted from 2003 to 2006, prior to the standard use of boosted PI regimens. Results indicated that 50% of participants became adherent and had suppressed viral loads to less than 50 copies per milliliter at the 3-month postintervention follow-up time point. Of those who became adherent, 79% remained adherent at the 12-month postintervention follow-up time point. Implementation of the intervention was found to be feasible in a real-world setting and participants reported that they liked the intervention. A 6-session length of the intervention was found to have the same impact on adherence outcomes as a 12-session length. No differences were found in outcomes with regard to the intervention's start time: before or at the same time the new antiretroviral regimen was initiated. These results suggest that the READY intervention may have merit and that the 6-session length may be more acceptable. However, a larger controlled study is indicated to examine intervention efficacy further.

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retrovirology

HIV-1 exploits importin 7 to maximize nuclear import of its DNA genome
Background

Nuclear import of the HIV-1 reverse transcription complex (RTC) is critical for infection of non dividing cells, and importin 7 (imp7) has been implicated in this process. To further characterize the function of imp7 in HIV-1 replication we generated cell lines stably depleted for imp7 and used them in conjunction with infection, cellular fractionation and pull-down assays.

Results

Imp7 depletion impaired HIV-1 infection but did not significantly affect HIV-2, simian immunodeficiency virus (SIVmac), or equine infectious anemia virus (EIAV). The lentiviral dependence on imp7 closely correlated with binding of the respective integrase proteins to imp7. HIV-1 RTC associated with nuclei of infected cells with remarkable speed and knock down of imp7 reduced HIV-1 DNA nuclear accumulation, delaying infection. Using an HIV-1 mutant deficient for reverse transcription, we found that viral RNA accumulated within nuclei of infected cells, indicating that reverse transcription is not absolutely required for nuclear import. Depletion of imp7 impacted on HIV-1 DNA but not RNA nuclear import and also inhibited DNA transfection efficiency.
Conclusions

Although imp7 may not be essential for HIV-1 infection, our results suggest that imp7 facilitates nuclear trafficking of DNA and that HIV-1 exploits imp7 to maximize nuclear import of its DNA genome. Lentiviruses other than HIV-1 may have evolved to use alternative nuclear import receptors to the same end.

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CDC

Causes of Death in HIV-infected Persons Who Have Tuberculosis, Thailand
Up to 50% of persons with HIV and a diagnosis of tuberculosis (TB) in Thailand die during TB treatment. In a prospective observational study, a team of physicians ascribed the cause of death after reviewing verbal autopsies (interviews of family members about events preceding death), laboratory data, and medical records. Of 849 HIV-infected TB patients enrolled, 142 (17%) died. The cause of death was TB for 38 (27%), including 6 with multidrug-resistant TB and 20 with disseminated TB; an HIV-associated condition other than TB for 50 (35%); and a condition unrelated to TB or HIV for 22 (15%). Twenty-three patients (16%) were judged not to have had TB at all. Death from all causes except those unrelated to TB or HIV was less common in persons receiving antiretroviral therapy (ART). In addition to increasing the use of ART, death rates may be reduced through expanded use of modern TB diagnostic techniques.

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esciencenews

Mathematical models reveal how organisms transcend the sum of their genes
Molecular and cellular biologists have made tremendous scientific advances by dissecting apart the functions of individual genes, proteins, and pathways. Researchers at the University of Wisconsin-Madison College of Engineering are looking to expand that understanding by putting the pieces back together, mathematically. John Yin, a professor of chemical and biological engineering, developed computer models of a relatively simple virus to show that genes alone do not make an organism. With mathematical representations of the virus's known biology, he and former graduate student Kwang-il Lim demonstrate how genomic organization and regulation can have a large impact on biological outcomes. As shown in a new paper, simply shuffling the order of the five genes in the virus's genome has a huge impact on how well the virus grows and how it interacts with its simulated host cell.

Their new results are reported Friday, Feb. 6, in the journal PLoS Computational Biology at http://dx.doi.org/10.1371/journal.pcbi.1000283.

The work has many potential applications. Understanding how to control the virus's growth and infectivity will help guide efforts to develop VSV as a cancer-targeting agent and create vaccines against more problematic viruses such as HIV-1 and influenza.

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medicalnewstoday

Wall Street Journal Examines Unsafe Injection Practices That Could Spread HIV, Other Diseases
The Wall Street Journal on Wednesday examined unsafe injection methods sometimes practiced in clinics and hospitals that can spread HIV, hepatitis and other bloodborne diseases. According to the Journal, most health care providers are aware of the risks associated with reusing needles; however, some medical workers do not follow other injection guidelines, such as discarding syringes after each use. If a health worker reuses either a syringe or a needle after administering an injection to someone who has HIV, hepatitis or another disease, they risk transmitting that disease to another patient. In addition, using an unclean needle or syringe to draw out medication from a multiple-dose vial can contaminate the vial itself and put future patients at risk.

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Offline John2038

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Re: John2038's Research News
« Reply #248 on: February 06, 2009, 01:41:58 AM »
Conference on Retroviruses and Opportunistic Infections Starts Sunday in Montreal



The 59th Conference on Retroviruses and Opportunistic Infections (CROI 2009) will take place next week, February 8-11, in Montreal, Canada.

As one of the most prominent international scientific meetings on HIV/AIDS, many researchers choose CROI as the venue for presenting their latest research.

While no breakthrough HIV drugs are nearing approval this year, the conference will feature several sessions on shifting antiretroviral therapy strategies, including the benefits and drawbacks of earlier treatment.

CROI 2009 will also include presentations dealing with complications of antiretroviral therapy, biomedical HIV prevention methods, and management of HIV/AIDS and opportunistic infections in resource-limited settings.

Abstracts and selected presentations will be available on the conference web site, here as content is released from embargo next Monday through Wednesday.

Offline John2038

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Re: John2038's Research News
« Reply #249 on: February 07, 2009, 12:44:05 PM »
bizjournals

Sales of Trimeris' Fuzeon fall 39% in 4Q
Global sales of Trimeris’ AIDS drug, Fuzeon, fell by 39 percent in the fourth quarter, continuing the treatment’s downward trend.

Trimeris (Nasdaq: TRMS), based in Durham, says worldwide net sales of the treatment were $40.5 million, down from $66.5 million in the fourth quarter of 2007.

Net sales in the U.S. and Canada were $16.1 million, down 49 percent from a year earlier. Outside the U.S., sales were $24.4 million, down 30 percent from the same period in 2007.

For all of 2008, Fuzeon sales were $167 million, down from $267 million in 2007.

Trimeris co-promotes Fuzeon with the Swiss pharmaceutical company Roche. The drug’s sales were poached in 2008 by new AIDS treatments from big pharmaceutical companies including Pfizer, Merck and Gilead Sciences.

Trimeris, once a Wall Street darling whose shares fetched more than $70 at the height of the stock market bubble in 2000, has seen its fortunes turn around since then. The company remains profitable. But the blockbuster sales many thought would come for Fuzeon never came. Efforts to bring other drugs to the market stalled.

Earlier this year, the company shut down all research efforts after finishing early-stage human trials of TRI-1144, a more potent version of Fuzeon. It also has laid off all but a small handful of workers and returned the majority of its cash to investors in the form of special dividends.

Source


AEGIS

HAART and cervical abnormalities—a long-term study
Like HIV, the human papillomavirus (HPV) is also sexually transmitted. As a result, many HIV positive men and women are co-infected with both viruses. Infection with HPV can cause warts in or around the genitals and anus. More troublingly, HPV can also cause abnormal growths on the cervix, vulva, penis and inside the anus. In some cases, these abnormal growths can transform and become pre-cancerous and can even form tumours.

As HIV weakens the immune system, HPV infection tends to persist; therefore, co-infected women can have high rates of abnormal cervical growths and cervical cancer compared to HIV negative women.

In high-income countries, highly active antiretroviral therapy (HAART) is generally widely available. This therapy reduces the production of new HIV, allowing the immune system to begin to rebuild itself. Consequently, life-threatening infections—the hallmark of AIDS—are uncommon in people who are engaged in their medical care and treatment in these countries.

In one study, researchers in the United States have been closely monitoring the gynecologic health of HIV positive women, in some cases for up to seven years. They found that in some women the use of HAART might enhance the ability of the immune system to control HPV.

Study details

The team of researchers began recruiting hundreds of HIV positive women and other women at high risk for HIV infection in 1993. Study clinics were located in the following American cities:

    * Baltimore
    * Detroit
    * Bronx
    * Providence

Women were seen twice yearly at study clinics where they were extensively interviewed, underwent physical and gynecologic examinations and had blood and other fluids collected for analysis. During these visits, Pap tests were performed and women with abnormal results received further gynecologic care as necessary.

The study team focused on 537 HIV positive women, about half of whom had never used HAART. The average profile of these participants at the time they entered the study was as follows:

    * age – 35 years
    * 50% had injected street drugs
    * main ethno-racial distribution: 60% Black, 22% White, 16% Hispanic
    * 71% currently smoked cigarettes
    * 60% of the women had detectable HPV on their cervix using high-tech PCR tests
    * most women had CD4+ counts between 200 and 499 cells
    * only 6% of women had a viral load below the 50-copy mark

Results

Women who had moderately abnormal Pap test results and who used HAART seemed mostly likely to clear HPV cervical infection.

But in women who had mildly abnormal Pap test results, HAART did not seem to help their immune systems clear HPV.

Overall, women taking HAART were 30% less likely to have worsening Pap test results. Moreover, HAART users were 30% more likely to have Pap tests results improve over the course of the study.

Don’t miss the Pap

The study authors caution that while HAART appears to help the immune system clear HPV and reduce the severity of HPV disease, these effects do not happen quickly nor is cervical health fully restored. Therefore, HIV positive women continue to need regular and close gynecologic care so that abnormal growths can be caught early in their development.

Source


aidsmap

Gay men should have rectal tests for chlamydia as part of routine sexual health care
A study was designed by researchers from the hospital with three aims:

    * To determine the prevalence of rectal chlamydia amongst gay men.
    * To find out how many of these infections were asymptomatic.
    * To establish the number of infections that would have remained undiagnosed had routine
       screening not been introduced.

The study was conducted between 2005 and 2006 and included a total of 3076 men. All these men had urethral screens for chlamydia and 3017 had rectal swabs for the infection.

Results showed that 8% of men had rectal chlamydia with 5% having urethral chlamydia. The prevalence of chlamydia was higher than any other infection, with tests showing that 4% of men had rectal gonorrhoea, 5% had urethral gonorrhoea and 3% syphilis.

The investigators then looked at the cases of chlamydia in more detail. Of the 397 men diagnosed with chlamydia, 62% (247) were infected rectally, 42% (165) had urethral infection and 4% (15) had the infection in both sites.

Rectal infection with chlamydia was asymptomatic in 69% (171) men and would therefore have been missed without routine screening. Only 8% of asymptomatic men also had urethral infection.

Rectal LGV was diagnosed in 14% (35) of the men with rectal chlamydia. There was also one case of urethral LGV. The vast majority of rectal LGV cases (82%) were symptomatic.

There was a high prevalence of HIV infection in men with rectal chlamydia (38%, 94 individuals). The investigators also note that twelve men were first diagnosed with HIV at the same time as rectal infection with chlamydia was detected.

Factors significantly associated with rectal chlamydia were HIV infection (p < 0.01), rectal gonorrhoea (p = 0.0002) and genital warts (p = 0.016). The investigators excluded men with LGV from their statistical analysis, but they still found a significant association between rectal chlamydia and HIV (p = o.004) and rectal chlamydia with rectal gonorrhoea (p = 0.002).

“Our data shows a higher rate of rectal chlamydia infection compared to gonorrhoea, a significant proportion of which were asymptomatic”, write the investigators.

They conclude, “current STI guidelines in the UK only recommend routine screening for rectal gonorrhoea but not rectal chlamydia and our data support the need to revisit these guidelines. We recommend routine screening for rectal chlamydia in men who have sex with men at risk of acquiring this infection.”

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NATAP

Does Early Antiretroviral Treatment Prevent Liver Fibrosis in HIV/HCV-Coinfected Patients ?
In this study of 395 HIV/HCV-coinfected patients, the interval between diagnosis of HIV infection and initiation of antiretroviral therapy was longer among patients with significant fibrosis (F3-F4). These latter patients were less likely to be antiretroviral naive and had received antiretroviral therapy for longer than patients with mild fibrosis. This suggests that it is not the prescription or duration of HAART that protects from hepatic fibrosis but rather its early initiation after diagnosis of HIV infection. Our results are in line with those of 2 recent studies. Verma et al8 also found that fibrosis progressed more slowly in patients who started HAART early after HIV diagnosis. Likewise, Marine-Barjoan et al9 found that the interval between the presumed date of HCV infection and HAART initiation was significantly longer among patients with severe fibrosis than among patients with no fibrosis or moderate fibrosis. A recent study suggests that cytotoxic CD8 T-cell accumulation, and associated release of inflammatory mediators, may augment liver damage (mainly fibrosis) in HIV/HCV-coinfected patients.10 The protective effect of HAART on liver damage could thus be linked to an attenuation of inflammation. Independent links have been reported between hepatic fibrosis progression on the one hand and CD4 cell depletion and HIV nonsuppression on the other hand.3,11 However, we found no significant association between severe fibrosis and the CD4 cell count, the CD4 cell nadir, prior CD4 cell counts below 100 cells per cubic millimeter, the Centers for Disease Control and Prevention class of HIV disease, or detectable HIV viral load.

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GSK Acquires New HIV NNRTI IDX899 From Idenix
Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX) and GlaxoSmithKline (GSK) today announced the execution of a license agreement granting GSK exclusive worldwide rights to IDX899.

About IDX899
 
IDX899 is a potent non-nucleoside reverse transcriptase inhibitor (NNRTI) being developed for the treatment of HIV-1. Idenix has advanced IDX899 through a Phase II proof-of-concept study in HIV-1 infected treatment-naive patients that was completed in 2008. In the proof-of-concept study, patients (n=32) receiving once-daily oral administration of IDX899 achieved mean viral load reductions of 1.8 log(10), after seven days of treatment as tested with the Roche Amplicor(R) 1.5 assay. In this study, no treatment-related serious adverse events were reported and no patients discontinued. The most common adverse events observed were dyspepsia, headache and nausea; the rate of these events was similar between IDX899-treated patients and those receiving placebo. Additionally, no patterns in laboratory abnormalities between treatment groups were observed during the treatment period.

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Is Dual Therapy With Raltegravir and Protease Inhibitors a Feasible Option in Rescue Strategy in HIV-1 Infection ?
Since the advent of highly active antiretroviral therapy, the rule of 3-drug combinations has become a well-recognized need in the treatment of HIV-1 infection. Two-drug combinations always proved to be less effective,1,2 and 4 drugs have been so far found to be no better than 3.3 However, in the salvage setting, the concepts of active drugs and genotypic sensitivity score flanked and often substituted this simple rule.4 Although rescue drugs generally seem to be effective in the presence of a genotypic sensitivity score (GSS) = 2 in the optimized background regimen (OBR),5 in the Benchmrk trials, the integrase inhibitor raltegravir has shown to suppress HIV RNA to <50 copies per milliliter in 67% of the subgroup of patients having a GSS = 1 in their OBR at a follow-up of 24 weeks.
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Use of Saliva as a Lubricant in Anal Sexual Practices Among Homosexual Men
Our findings provide the rationale for formal investigation of whether saliva used as a lubricant in anal sex may contribute to the transmission of saliva-borne pathogens in MSM. Until it can be disproved that saliva-borne pathogens are transmitted through this route, there now needs to be debated as to whether prevention guidelines should be expanded to include avoidance of saliva exposure via this route.....Education alone regarding the risks of saliva use in this manner may be all that is needed to facilitate behavior change. Structural interventions, such as the copackaging of condoms with packets of sterile jelly lubricants, might also be useful in sustaining the message. This debate will likely only be settled through collection of more epidemiologic data directly examining the infectivity of saliva when used as a lubricant and novel data from the community on the perceived consequences among MSM of a message that suggested avoidance of the use of saliva in this way.

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huliq

Study on slow progressors to investigate new treatments for HIV
Why do some HIV patients manage to control the progression of their infection naturally over long periods of time? As part of a nation-wide investigation, a team of researchers will examine that question and others as they work to develop new strategies to fight AIDS.

The five-year study will be headed by Dr. Cécile Tremblay, a physician and investigator with the Centre hospitalier de l'Université de Montréal's Research Centre (CRCHUM) and a professor at the Université de Montréal, thanks to nearly $1 million in support from the Canadian Institutes for Health research (CIHR).

In light of a limited success in developing vaccine therapies, it has become clear that the scientific community needs to place greater emphasis on the basic research necessary to address the many unanswered questions that remain about HIV. One of the best approaches to try to develop effective vaccines is the study of HIV-infected individuals who control their infection naturally and do not show disease progression over a long period of time. Called slow progressors (SP), these individuals make up less than 1percent of HIV-infected population. Some of the questions that this study will address include:

What constitutes a protective immune response?
What are the drivers of HIV diversity?
Can we develop broadly neutralizing antibodies?
And, ultimately, how can this understanding lead to the development of an effective vaccine?
Conducting a study of this nature requires a sufficiently large pool of slow progessors. Enter Dr. Tremblay, whose team has assembled a unique cohort of slow progessors in Quebec and, thanks to the CIHR funding, she will expand it throughout Canada. This national effort will involve the collaboration of major HIV clinical scientists across the country, including in Toronto, Vancouver and Victoria, as well as international colleagues.

The cohort will enable researchers to gather important information concerning the clinical course of HIV, which may lead to the identification of factors that predict a favourable outcome. The study will enable the collection of samples that will be stored in a specimen bank, which will be made available to various investigators investigating the progression of HIV.

The project aims to determine the natural history of the disease over a five-year period. It will also focus on the impact of viral genetic evolution on the immune system through the collection of clinical, demographic, social and behavioural data that will be analyzed in correlation with virological, immunological and genetic findings.

By University of Montreal

Source
« Last Edit: February 07, 2009, 02:37:37 PM by John2038 »

 


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