Bimazek's Research News

[bimazek]

Two great new stories...

investigational integrase inhibitor elvitegravir

Elvitegravir is a dihydroquinoline carboxylic acid strand inhibitor of HIV integrase

Elvitegravir is a dihydroquinoline carboxylic acid

what it does is a strand inhibitor of HIV integrase

I am very excited about all these new -- call them -- second generation meds, that have lower toxicities and less side effects, they give me great hope, but i was curious as to what this substance was, where it came from what was it related to, obviously it is from natural substances here in the ground, i had a chem. professor in the family so i wanted to learn more and the findings are very re-assuring, to me at least, because the nukes and non nukes, seem scary in thier history and side effects, these new ones seem more specialized and rare yet somehow familiar and historic.  after reading about this one it seems less mysterous and more acceptable

dihydroquinoline carboxylic acid

Quinoline - Wikipedia, the free encyclopediaQuinoline, also known as 1-azanaphthalene, 1-benzazine, or benzopyridine, is a heterocyclic aromatic organic compound. It has the formula C9H7N and is a ...
en.wikipedia.org/wiki/Quinoline

http://www.chemicalland21.com/specialtychem/finechem/QUINALDINE.htm  Quinaldine, 2-methylquinoline, is used as an anti-malaria and preparing other anti-malaria drugs. It is used in manufacturing oil soluble dyes, food colorants, pharmaceuticals, pH indicators and other organic compounds. Quinaldic Acid is a carboxylic acid substituted quinoline at 2 position, a catabolite of tryptophan (aromatic side chain amino acid). Quinazoline, diazanaphthalene at 1,3 positions, is used as a chemical intermediate for making medicines and other organic compounds. It is a fundamental structure in some antihypertensive agents such as prazosin and doxazosin which are peripheral vasodilator. Quinoxaline, diazanaphthalene at 1,4 positions, is used as a chemical intermediate for making fungicides and other organic compounds

http://chemicalland21.com/industrialchem/organic/QUINOLINE.htm#

carboxylic acid
http://en.wikipedia.org/wiki/Carboxylic_acid

http://www.chemicalland21.com/specialtychem/finechem/QUINALDINE.htm
Quinoline itself is the simplest member of the quinoline. It is a hygroscopic, liquid; slightly soluble in water, soluble alcohol, ether, carbon disulfide and readily in many organic solvents. It can be obtained by the distillation of coal tar. Quinoline family compounds are widely used as a parent compound to make drugs (especially anti-malarial medicines), fungicides, biocides, alkaloids, dyes, rubber chemicals and flavoring agents. They have antiseptic, antipyretic, and antiperiodic properties. They are also used as catalyst, corrosion inhibitor, preservative, and as solvent for resins and terpenes.
originally discovered in the distillation of coal tar.


monoclonal antibody PRO 140

this is a major major breakthru

The antibody PRO 140 produced a quick and prolonged reduction in viral load starting within five days. Some patients on the drug had a reduction by a factor of 10. After 10 days the average reduction was close to a factor of 1,000. Additionally, "the decline persisted for two to three weeks", Dr. Jacobson said.
http://www.associatedcontent.com/article/386600/new_monoclonal_antibody_blocks_hiv.html





this answers the question of a few months ago that we were posting about very simply and not too dramatically

60% greater risk of developing a non-AIDS-defining cancer for HIV-positive

http://www.aidsmap.com/en/news/55D50883-6979-4993-AC0A-53CFFA8F86F8.asp
A total of 33,420 HIV-infected patients were followed for a median of 5.1 years, with 66,840 HIV-negative individuals followed for a median of 6.4 years.  Incidence rates of non-AIDS-defining cancers were 1260 per 100,000 person years in HIV-positive patients and 841 per 100,000 person years in HIV-negative patients. This corresponds to a 60% greater risk of developing a non-AIDS-defining cancer for HIV-positive versus HIV-negative patients (incidence rate ratio [IRR], 1.6; 95% CI: 1.5 – 1.7). The incidence of anal cancer (IRR 14.9; 95% CI: 10.1 – 22.1), Hodgkin’s lymphoma (IRR: 4.6; 95% CI: 3.6 – 6.6), liver cancer (IRR: 2.8; 95% CI: 2.2 – 3.5), and lung cancer (IRR 2.0; 95% CI: 1.7 – 2.2) were particularly elevated in HIV-positive individuals compared to HIV-uninfected patients.

[bimazek]

2006 article about new peptide assays for epitope discovery and vaccine research tool made by Sigma-Genosys (www.sigma-genosys.com

this article describes why vaccine research has been moving ahead recently because new tools to try lots of different epitopes or fragments can be produced using this companies tools

A major challenge in the development of vaccines is the difficulty of finding the right immunogenic element that can achieve an efficient and long-lasting immunization effect. Considerable effort has been made to find suitable fragments (protein epitopes) that can be included in vaccines to offer protection against serious life-threatening diseases.

http://www.genengnews.com/articles/chitem.aspx?aid=1882

peptide synthesis was historically an expensive choice in vaccine research and epitope mapping. However, a new synthesis platform from Sigma-Genosys (www.sigma-genosys.com) allows the rapid parallel synthesis of custom libraries at reduced costs, giving access to high-throughput synthetic peptide assays for epitope discovery and vaccine research.  Epitope Mapping with Peptide Libraries

HIV exemplifies the time-consuming and difficult nature of vaccine discovery.

As CD8+ T cells have been shown to play an important role in containing HIV infection, vaccine development has focused on the biological mechanism of CD8+ T-cell responses upon HIV infection.

[bimazek]

Investigators Engineer T Cells against B-Cell ... this technique now proven in this study will be tried against any number of diseases now and in future, it is a nice new growth in science and could have some great and interesting results for hiv, seems to be a whole new branch of treatment, not vaccine, not medicine, in a way it is genetic engineered but not really old style gene therapy, call it immune system T cell engineering or immune system T cell gene modification

http://www.genengnews.com/news/bnitem.aspx?name=23253604&source=genwire

Investigators Engineer T Cells against B-Cell Malignancies
Sep 18 2007, 12:34 PM EST

GEN News Highlights

Modified T cells can be effective in fighting cancers associated with B cells such as acute lymphoblastic leukemia (ALL), according to researchers at Memorial Sloan-Kettering Cancer Center (MSKCC). By administering repeated doses of T cells designed to express an artificial receptor that recognizes human B cells, the researchers say that they were able to eradicate cancer in 44% of mice bearing human ALL tumors.

[bimazek]

gag region -- vaccine researchers should focusing on it


13 Sep 2007
a vaccine containing the correct part of the gag gene could activate the body's immune response and increase its ability to stop HIV-2 from progressing to AIDS. According to Aleksandra Leligdowicz, who leads the MRC unit, the latest research suggests that it is possible to create a vaccine that will not prevent infection or eradicate the virus but that could prevent progression to AIDS. "Clearly there is something special about the gag region -- and it looks like vaccine researchers should be focusing on it," Leligdowicz said. Most strains of HIV-1 also have a gag gene, according to Leligdowicz, who added that the 2% of people who test positive for HIV-1 and do not progress to AIDS also demonstrate a strong immune response to the gene

http://www.medicalnewstoday.com/articles/82159.php

[bimazek]

http://afp.google.com/article/ALeqM5ju0Xe3NMXSNs_si-VJRa47qKY51Q

"These findings may serve as the basis for a new strategy to develop a new class of anti-HIV drugs, the splicing inhibitors, and even of antiviral drugs in general, since any virus needing to splice its RNAs may be targeted," his team writes.

However, exhaustive tests on lab animals, leading to cautious trials on humans, are needed before IDC16 can be certified as safe and effective. This process typically takes years.

good new dev. on the p-mRNA area will be year out in future ... but every good step helps

[bimazek]

Wow -- this is fantastic -- this is a new trial with very exciting words... the trial with this med MDX-1106 for melanoma cancer must have worked well enough for them to want to try a viral cancer disease like hepatitis and the fact that it is in trials is life saving!!!  I wont even mention that this is anti-pd-1 fully human monoclonal antibody.   If you have cancer from hep C try to get in this trial. 

http://www.medarex.com/cgi-local/item.pl/20071029-1069064
Oct. 29 2007
Medarex, Inc. (Nasdaq: MEDX) announced today the allowance of an investigational
new drug application (IND) filed with the U.S. Food & Drug Administration (FDA)
for MDX-1106 (ONO-4538: development code of Ono Pharmaceutical Co., Ltd.), a fully
human anti-PD-1 antibody being investigated for the treatment of chronic viral
infections, with the first trial to target hepatitis C. MDX-1106 was developed under
the May 2005 collaborative research agreement between Ono and Medarex, and currently
is in a separate ongoing Phase I clinical study  in patients with recurrent or
treatment- refractory cancer.    "Recently, involvement of PD-1 in hepatitis C has been reported in the
scientific literature," said Shozo Matsuoka, Ph.D., Senior Managing Director of Ono
Pharmaceutical, Co., Ltd. "ONO-4538/MDX-1106 aims to improve the immune capacity of
the body and treat hepatitis C with a novel mechanism of action which inhibits the
involvement of PD-1. We are seeking to develop ONO- 4538/MDX-1106 to be a new
treatment for hepatitis C."


http://www.rttnews.com/sp/Quickfactsnew.asp?date=10/29/2007&item=228

FDA Allows Ono And Medarex' Investigational New Drug Application For Fully Human Anti-PD1 Antibody [MEDX]

10/29/2007 5:03:39 PM Ono Pharmaceutical Co., Ltd. (OPHLF.PK) and Medarex, Inc. (MEDX) announced the allowance of an investigational new drug application filed with the U.S. Food & Drug Administration for MDX-1106, a fully human anti-PD-1 antibody being investigated for the treatment of chronic viral infections, with the first trial to target hepatitis C.


"treatment of chronic viral infections, with the first trial to target hepatitis C. "
this phrase is so so beautiful to me... because it is a very strong statement for a public drug company, it is a strong hint that in the future other   chronic viral infections   may be in trials and treated with this drug...
um lets see -- what chronic viral infection do we know is hugely impacted by this type of treatment
HIV
this could be an amazing hopeful thing, and they are moving to new clinical trials,
the first one was melanoma of the skin, rather easy to see the good effects, if the protein the monoclonal antibody protein works then the skin lesion gets smaller, very easy to see good results, this trial was so successful, they went back to FDA and with the results got approval to try  with

chronic viral infections

first of which will be HepC cancer

BTW the word for cancer and tired are the same in latin and the latin language portugese.
i guess in anchient days being tired all the time was thought of as a cancer.

this is very very exciting to me and i must say that this could mean some great things

this means that the dose they were giving to melanoma patients was fine and did not have any bad adverse effects of the horrible kind, so the FDA is letting them try it on more deep and hidden disease.

kudos to who?

[bimazek]

Articles on HIV found by Google Scholar

In 2007 in Science articles that talk about HIV

26,300 articles in google scholar when we Search only in Medicine, Pharmacology, and Veterinary Science.
   476 articles in Computer Science, and Mathematics. about HIV
 2,290 articles in Chemistry and Materials Science.
    82 articles for hiv. Search only in Physics,

Search only in Engineering, Computer Science, and Mathematics.    476 for hiv
http://scholar.google.com/scholar?hl=en&lr=&q=hiv&as_ylo=2007&as_yhi=2007&btnG=Search&as_allsubj=some&as_subj=eng

 2,290 for hiv
Search only in Chemistry and Materials Science.
http://scholar.google.com/scholar?hl=en&lr=&q=hiv&as_ylo=2007&as_yhi=2007&btnG=Search&as_allsubj=some&as_subj=chm

 26,300 for hiv
Search only in Medicine, Pharmacology, and Veterinary Science.
http://scholar.google.com/scholar?as_q=hiv&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=&as_publication=&as_ylo=2007&as_yhi=2007&as_allsubj=some&as_subj=med&hl=en&lr=

82 for hiv. Search only in Physics, Astronomy, and Planetary Science.
http://scholar.google.com/scholar?q=hiv&hl=en&lr=&as_ylo=2007&as_yhi=2007&as_subj=phy&start=10&sa=N

 8,670 for hiv  Search only in Social Sciences, Arts, and Humanities.
http://scholar.google.com/scholar?as_q=hiv&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=&as_publication=&as_ylo=2007&as_yhi=2007&as_allsubj=some&as_subj=soc&hl=en&lr=

Search only in Business, Administration, Finance, and Economics.
717 for hiv
http://scholar.google.com/scholar?as_q=hiv&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=&as_publication=&as_ylo=2007&as_yhi=2007&as_allsubj=some&as_subj=bus&hl=en&lr=

Each of these articles had a team of writers and researchers.
Also staff and secretaries, deans, and admin, and wives and husbands.

In can only be said that a vast effort by much of mankind is trying to solve this terrible disease, and every day they get closer

Just based on the recent successes in the vaccine trials, (not that one failure) and also gene, and many many new drug modalities

I must say that I agree, if someone is exposed today they should count on a normal lifespan and normal functionality.

For those infected ten and twenty years ago there are so many new new things coming out please work hard to stay in the game we all need you.  And dont forget to give your time to those newly infected we all need you too.

71,700 for hiv total articles in all areas

hope this find interesting stuff for you

many interesting areas of research
into HIV

[bimazek]

ok here is the scoop, science discovered in last few years that 9% of the entire human genome is RETROVIRUSES that got stuck in the dna in the last 700 million years of evolution

literally every human has tons of virus code dna in thier bodies at birth from the time we were lower animals

sounds amazing but true

now they also discovered that sometimes one of these dna fragments called

endogenous retroviruses (HERV)

break free of the cell and start to multiply and in some cases cause some horrible very rare diseases, so rare that only like 23 people in usa get them a year and science didnt know what caused them till recently

anyway

NOW they have found a way

well first i should say that the body immune system since it has evolved with these DEEP dna retroviruses inside the human is very very good at keeping them suppressed in like 99.999% of humans

the dna is there but the molecules of immune system keep them shut up

so the new thing they found is that

they can use the part of the immune system that
DOES SUCH A GREAT JOB OF SUPPRESSING THE   
DEEP
endogenous retroviruses (HERV)

THAT THEY CAN harness this part of immune system to fight HIV

and it works well

so they can make a vaccine with this info

it is a few years off but could pay off big in HIV and other rare rare terrible diseases.

http://www.google.com/search?hl=en&q=Novel+HIV+Vaccine+Target+Discovered&btnG=Google+Search

Novel HIV Vaccine Target Discovered
Nov 9 2007,

GEN News Highlights

Researchers identified a potential new way of fighting HIV infection that relies on the remnants of ancient viruses, human endogenous retroviruses (HERV).  Mounting evidence suggests that HIV infection could enable HERV expression by disrupting the normal controls that keep HERV in check. In some HIV-infected individuals this induces infection fighting T cells to target HERV expressing cells.

 "HERV-specific CD8+ T cells have characteristics consistent with an important role in the response to HIV-1 infection: a phenotype similar to that of T cells responding to an effectively controlled virus (cytomegalovirus), an inverse correlation with HIV-1 plasma viral load, and the ability to lyse cells presenting their target peptide,” 
“These characteristics suggest that elicitation of antiHERV-specific immune responses is a novel approach to immunotherapeutic vaccination. As endogenous retroviral sequences are fixed in the human genome, they provide a stable target, and HERV-specific T cells could recognize a cell infected by any HIV-1 viral variant,”


http://en.wikipedia.org/wiki/Endogenous_retrovirus
It is believed that the ancestors of modern vivipary mammals evolved after an accidental infection to an ancestor to this virus, that permitted to the fetus to survive the immune system of the mother. [1]
During pregnancy in viviparous mammals (all mammals except Monotremes), ERVs are activated and produced in high quantities during the implantation of the embryo. They are currently known to act as immunodepressors, protecting the embryo from its mothers immune system. Also viral fusion proteins apparently cause the formation of the placental syncytium in order to limit the exchange of migratory cells between the developing embryo and the body of the mother (something an epithelium will not do sufficiently, as certain blood cells are specialized to be able to insert themselves between adjacent epithelial cells)

[bimazek]

http://freshnews.com/news/biotech-biomedical/article_40893.html

DNA Vaccine Overview at Scientific Meeting

DNA vaccines have the potential to by-pass inherent scientific obstacles of conventional vaccines that prevent their development for cancer and chronic infectious diseases such as HIV and hepatitis C. Pre-clinical data has indicated the ability of Inovio’s technologies to effectively deliver and significantly enhance the potency of such immunotherapies without the potential safety concerns of viral delivery systems.

[bimazek]

http://www.freshnews.com/news/biotech-biomedical/article_40886.html?

Invitrogen and CytRx Subsidiary Rxi Pharmaceuticals Collaborate to Enhance RNAi

http://www.cytrx.com/vaccine_overview.html

http://www.cytrx.com/hiv_program.html

[bimazek]

http://freshnews.com/news/biotech-biomedical/article_40943.html

  Dr. Taylor documented that 60% of circulating exosomes were removed from the blood of ovarian cancer patients during first pass (approximately 10-minutes) through a small scale Hemopurifier®. The capture data was consistent over the course of five different studies.

Hemopurifier® efficiently captures tumor secreted exosomes that inhibit the ability of the immune system to combat cancer. In follow-on studies, led by Dr. Douglas Taylor at the University of Louisville, it has now been demonstrated that the capture of exosomes by the Hemopurifier® does result in reversing immunosuppressive activity. Dr. Taylor is a recognized authority on the causative effects of immune suppression in cancer patients. He is credited with the initial characterization of exosomes and is a leading peer reviewed author on the subject.
   
   “Based on emerging data, we envision the Hemopurifier® will become a treatment standard that enhances the benefit of therapies administered to those who suffer from cancer,” stated James A. Joyce, Chairman and CEO of Aethlon Medical.



http://www.imquest.com/hiv-agent.shtml

http://freshnews.com/news/biotech-biomedical/article_40882.html

http://www.aethlonmedical.com/technology/hemopurifier.htm
http://www.aethlonmedical.com/technology/reports.htm
 








   Aethlon Medical is the developer of the Hemopurifier®, a first-in-class medical device to treat infectious disease. The Hemopurifier® addresses the largest opportunity in infectious disease, the treatment of drug and vaccine resistant viruses. Regulatory and commercialization initiatives in the United States are focused on bioterror threats, while international initiatives are directed towards naturally evolving pandemic threats, and chronic infectious disease conditions including Hepatitis-C (HCV) and the Human Immunodeficiency Virus (HIV). Collaborative studies to demonstrate utility of the Hemopurifier® are being conducted with researchers at the Government of India’s National Institute of Virology (NIV), The Centers for Disease Control and Prevention (CDC), The United States Army Medical Research Institute of Infectious Diseases (USAMRIID), and The Southwest Foundation for Biomedical Research (SFBR). Aethlon recently demonstrated safety of the Hemopurifier® in a 24-treatment human study and is now conducting follow-on human studies at the Fortis Hospital in Delhi, India. The Company has also submitted an Investigational Device Exemption (IDE) to the U.S. Food and Drug Administration (FDA) related to advancing the Hemopurifier® as a broad-spectrum treatment countermeasure against category “A” bioterror threats. Additional information regarding Aethlon Medical and its Hemopurifier® technology can be accessed online at www.aethlonmedical.com.

[Smoothstone]

My initial reaction is a skeptical. Internet sources, even from multiple sites can be a fraud. There are numerous internet scams which are quite clever citing impressive results, utilizing terms, referencing what seem to be credible institutions. utilizing several websites so there are multiple sources of the "breakthrough".   sometimes the institutions cited are credible but the product has no actual relationship. The scammers are getting increasingly sophisticated. Money to made. A worldwide market. An easy vehicle...the internet...and very difficult to track and get redress.

Those of us facing cancer and challenging medical conditions, especially some cancers with poor outcomes with limited or exhausted treatment options are desperate ducks...searching for hope.

Presto! A news report. . It started out with a news story and seemed credible and hopeful. Lucky it only cost me $70. Thanks. Hank

[Smoothstone]

Clarification: My bad experience was not in reference to the opportunity/development you cited. Hank

[bimazek]

http://www.genengnews.com/news/bnitem.aspx?name=26965488&source=genwire

one would think that this had already been known but it was not...  this is important because any fundamental important thing science learns about the immune system and the very cells we are all worried about can help in many areas

Cancer’s Ability to Evade Immune System Illuminated
Nov 20 2007, 12:07 PM EST

GEN News Highlights

Regulatory T cells can reverse the role of macrophages, which are normally involved in causing inflammation, report scientists at King’s College London.

http://www.genengnews.com/news/bnitem.aspx?name=26965488&source=genwire



Regulatory T cells =T regulatory cells are a component of the immune system that suppress immune responses of other cells. This is an important "self-check" built into the immune system so that responses do not go haywire. Regulatory T cells come in many flavors, including those that express the CD8 transmembrane glycoprotein (CD8+ T cells), those that express CD4, CD25 and Foxp3 (CD4+CD25+ regulatory T cells or "Tregs") and other T cell types that have suppressive function. These cells are involved in closing down immune responses after they have successfully tackled invading organisms and also in keeping in check immune responses that may potentially attack one's own tissues

[bimazek]

Here are hundreds of peer reviewed articles on this filter that science has been working on over years, and having some success
http://scholar.google.com/scholar?q=Aethlon+Medical&hl=en&lr=&btnG=Search

http://scholar.google.com/scholar?q=Hemopurifier&hl=en&lr=&btnG=Search

smoothstone i must answer your concerns because i only post if there is valid proven science behind things

there are tons of huge advances in cancer treatment and many clinical trials, the last 1,10, 20, years has shown huge leaps and new clinical trials, are you near a big research university like UCSF  or have you asked your doctor if there are any trials for your type of cancer, he may not know and you may have to find out and do some searching on the govt clinical trial website

[Smoothstone]

Thanks for the info. My skepticism is fueled by my loss of $70 sent via credit card in response to a scam involving news report, alleged experts giving testimony/credibility and quick product availability...

I am in SF with access to some clinical trials. A dilemma is that if you try one treatment now you often exempt yourself from future clinical trials of more promising treatments. In lung cancer, treatment options are beginning to expand beyond the chemo therapy radiation modes which  are pretty tough side effectwise, and have shown limited efficacy for most folks.  Hank.
 

[bimazek]

The Proprotein Convertase PCSK9, as a Potent Inhibitor of Hepatitis C Virus Replication
The Hepatitis C virus (HCV) is a worldwide leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, afflicting more than 180 million people worldwide. However, with current clinical treatment achieving viral clearance in only 50% of chronically infected patients, new treatment strategies for management of hepatitis C are urgently needed. Impeding advancements are some important mechanisms of HCV infection that are not fully understood, such as viral entry into hepatocytes. Recent focus has been on the tetraspan receptor CD81 and on the low density lipoprotein receptor (LDLR), which is known to play a part in HCV infection.

Proprotein Convertase PCSK9 plays a critical role in the regulation of lipid metabolism and cholesterol homeostasis through a reduction of the LDLR at the cell surface and the subsequent increase in circulating LDL-cholesterol in the blood stream.

We have identified PCSK9 as a very potent inhibitor of viral replication.

Results clearly indicate that Huh7 cells constitutively expressing PCSK9 are unable to sustain efficient HCV replication. The effect was even more pronounced when using PCSK9 chimeras harbouring an increased activity on LDLR and CD81 clearance from the cell surface. Significantly, the addition of purified soluble PCSK9 to the cell culture medium was also shown to prevent infection by HCV

quote from uventures.com
Knowledge Express, Pharma-Transfer, TechEx and Uventures,

[bimazek]

65% of adults have antibody to HSV-1
In homosexual and bisexual men with HIV infection, the rate of HSV-2 seropositivity is approximately 75%.

http://www.medscape.com/viewarticle/421019_4

Herpes Simplex Virus Infection
Human herpes virus infection is a common malady that is exacerbated by HIV infection. In the general United States population approximately 65% of adults have antibody to HSV-1 and 25% have antibodies to HSV-2.[58,59] HSV-2 behaves as a sexually transmitted disease with increased seroprevalence in post-pubescent adults. In homosexual and bisexual men with HIV infection, the rate of HSV-2 seropositivity is approximately 75%.[60,61]

[bimazek]

ok after reading this i think we have two very powerful concepts and discoveries here

first

"hematopoietic stem cells (HSC) - stem cells receive a lipid signal that enables them to exit into the thoracic duct. When the receptors on the stem-cell surface that detect pathogens become active, the cell’s ability to receive the lipid signal is blocked. The stem cells literally get stuck in the tissue, where they are then triggered to proliferate into immune cells,"

This could be analogous to why and how the strange fat build up occurs in viceral fat deposits, some lipid signal gone awry.-- not necessarily this lipid signal but one or another lipid signal

"hematopoietic stem cells (HSC) can divide and mature into immune system cells on the spot.
Scientists have known that a fraction of HSCs will sometimes migrate from the bone marrow into the bloodstream."

this could have an effect on why there is not a perfect correlation between VL, CD4 count etc
if there is a new just discovered part of the immune system that can pump powerful fresh versatile stem immune cells then this would have all kind of implications

anyone who is knowledgeable like the science guys and bio guys who post on here please add your comments-- how would this come into play in hiv disease and in the immune system

i recently read in another report that hair turns grey because the tiny stem cells at the base of the hair follicle die off or give out and they cant produce any new pigment cells -- this was a mystery for long time --
and i personally noticed that over the heart many men will get grey chest hair first in the area above and around the heart-- i made an assumption that this was because the tremendous strain and constant healing and repair that the heart must under go in all of us, uses up or burns out the stem cells that are in the chest hair follicals first --- just in same way that a childhood injury to the scalp can cause premature greying -- the chemical molecular healing that must occur constantly on the heart has a peripheral effect which is the stem cells in the hair follicles above the heart get effected too

questions -- would these newly discovered cells get involved in the attack against the cd4 cells, would that not be a strain on the system and the bone marrow that produces them, a constant



http://www.genengnews.com/news/bnitem.aspx?name=27325527&source=genwire

Scientists Find that Blood Stem Cells Are an Active Part of the Immune System
Nov 29 2007, 12:38 PM EST

GEN News Highlights

Harvard Medical School investigators found that upon encountering an invader, hematopoietic stem cells (HSC) can divide and mature into immune system cells on the spot.

Scientists have known that a fraction of HSCs will sometimes migrate from the bone marrow into the bloodstream. To understand why, they began by extracting lymph samples from the thoracic duct of a mouse, which routes the body’s excess fluids into circulation.

After screening, they discovered an extremely small population of blood stem cells. Further tests, which involved mice genetically engineered so that their blood stem cells could be detected through fluorescent microscopy, revealed that these cells were also scattered throughout visceral organs such as lthe iver, heart, and lungs.

“Taken all together, a picture developed suggesting that these cells migrated from the marrow and into the circulation where they would then leak out and enter the tissue,” says team leader, Steffen Massberg, M.D., a postdoctoral researcher and cardiologist. “After that, the thoracic duct would empty them back into the circulation, where they could re-enter the marrow.

“But the question was, why,” notes Dr. Massberg. “What exactly are they doing?” To figure this out, the researchers injected a bacterial endotoxin into the mouse tissue.

They found that after residing for a while in the organ tissue, the stem cells receive a lipid signal that enables them to exit into the thoracic duct. When the receptors on the stem-cell surface that detect pathogens become active, the cell’s ability to receive the lipid signal is blocked. The stem cells literally get stuck in the tissue, where they are then triggered to proliferate into immune cells, the scientists explain.

The paper will be published in the November 30 edition of Cell.

[bimazek]

it has been a month or two and no one posted anything on this
i see it as a big step forward

they are testing a new monoclonal antibody

can someone explain about drugs and monoclonal antibody

i heard that they use the monoclonal antibody to then later figure out what small molecule drug could do same thing but isnt as folded up and fragile as a monoclonal antibody which is a protein correct

this seems like a great step forward

treatment of chronic viral infections - why did no one post anything

first they used this new monoclonal antibody for melanoma cancer

now  treatment of the first chronic viral infection they are trying it on

my feeling is it will take a cocktail of monoclonal antibodies to treat of chronic viral infection

because the immune system is so complicated

what are your thoughts

great , good , or ho hum

and why

[bimazek]

Genentech big into auto­immune diseases research research spending 50% of the company's sales

auto­immune diseases, they afflict some 23.5 million Americans and are so disruptive for victims that they cost the U.S. health-care system $100 billion a year—nearly double the economic burden of cancer.

http://www.businessweek.com/magazine/content/07_51/b4063000924207.htm?chan=technology_technology+index+page_top+stories

Genentech's research spending to 50% of the company's sales—more than twice what most drug companies spend on R&D. The resulting stream of hit drugs pushed Genentech's sales up from $1 billion to $9 billion since 1999, and the company swung from a $1 billion loss that year to profits of $2 billion in 2006. Genentech's market cap soared past $75 billion,



genetech is putting big push on auto­immune diseases this would could help us because any money spent by big player on immune system has to help us eventually

i am going to study what hiv papers are published by this giant firm in 2007  peer reviewed hiv papers science papers
now  see what discoveries they are making in hiv this year

http://scholar.google.com/scholar?as_q=Genentech+hiv&num=100&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=&as_publication=&as_ylo=2007&as_yhi=2007&as_allsubj=all&hl=en&lr=


Results 1 - 100 of about 482 for Genentech hiv. (0.23 second  2007

here is a dec 5th 2007 article

HTLV-IIb reduces HIV infection  http://bloodjournal.hematologylibrary.org/cgi/reprint/109/5/1792
----------------------------------------------------------------------------------------------------------------
Davide Zella INSTITUTE OF HUMAN VIROLOGY
The article of Pilotti and colleagues aims to elucidate the anti-HIV mechanism(s)
related to HTLV-II coinfection in intravenous drug users (IDUs). The authors
demonstrate spontaneous production in vitro of an isoform of MIP-1 (CCL3L1)
in PBMCs from HTLV-II–infected subjects, and this isoform was the major determinant
of anti-HIV activity in coinfected HTLV/HIV subjects, possibly due to
interference with chemokine receptor CCR5. Additional studies provide indirect
evidence that the mechanism should act at a transcriptional level.
First isolated in association with a rare form
of hairy cell leukemia,1 and subsequently
classified in 2 different subtypes (a and b),
human T-lymphotropic virus type II (HTLVII)
has been associated with several lymphoproliferative
manifestations, although its direct
role in causing a disease has never been
unequivocally demonstrated. Based on evidence
in vitro and epidemiologic studies, it has
been speculated that type a could exert a more
detrimental role interacting with the immune
system than type b.
HTLV-II has been shown to be endemic
among various American-Indian populations
in North America, in Panama, and in South
America. HTLV-II can be transmitted in 3
ways          HTLV-II did not cause any
fast progression to acquired immunodeficiency
syndrome (AIDS) in IDUs, but on the
contrary it was surprisingly associated with a
delayed progression. It was only after the discovery
of chemokines as natural inhibitors of
human immunodeficiency virus (HIV) infection,
2 that the possible mechanism of
HTLV-II protective action started to be elucidated.
Indeed, an increased C-C chemokine
production in certain coinfected patients was
noted.3,4
The current article by Pilotti and colleagues
provides a better comprehension of
this mechanism. In fact, it appears that
HTLV-II infection triggers production of
CCL3L1, an isoform of MIP-1 that is primarily
responsible for protection (see figure).
This induction seems to act at a transcriptional
level, though the authors do not provide any
direct evidence to sustain this hypothesis. In
addition, other “protective” cytokines were
produced as a result of HTLV-II infection.
The effect was noted not only in stimulated
peripheral blood mononuclear cells
(PBMCs), but also in unstimulated cells. The
authors thus propose that HTLV-II confers a
protective state able to reduce susceptibility to
HIV infection.
More studies are needed to determine how
and why HTLV-IIb alters the cell programming
apparatus to induce production of CCL3L1,
protective cytokines, and a protective status
against HIV. Eventually, this might result in a
better understanding of the interactions between
the virus and components of the immune system.
It could also help in an understanding of
how to induce such a protective staus.






Genentech makes its first-ever acquisition - all 2 versions »
M Hollmer - Nature Biotechnology, 2007 - nature.com
... Tanner. Nor does he believe that the Tanox pipeline—including its HIV
drug candidate TNX 355—fits Genentech's strategy. Others





http://bloodjournal.hematologylibrary.org/cgi/content/full/109/10/4116
Indeed, the authors demonstrated profound perturbations in the levels of cytokines. They describe a vicious cycle, whereby activated cells are the source of cytokines that in turn activate new cells. This cycle may be embedded in a somewhat more general scheme including positive and negative feedback effects, as well as amplification of effector memory T cells (and of apoptosis) due to the rapid, transient proliferation and differentiation of activated cells2 (see figure). Thus, the higher proportion of lymph node T cells with effector-memory phenotype, reported here and elsewhere, may primarily be the result of increased turnover.





http://bloodjournal.hematologylibrary.org/cgi/reprint/109/11/4593
PD-1+ T cells: exhausted and premature? - all 2 versions »
L Su - Blood, 2007 - bloodjournal.hematologylibrary.org
... PD-1 up-regulation is correlated with HIV-specific memory CD8 + T-cell exhaustion
in ... Blood Online is supported in part by Genentech BioOncology and Biogen Idec. .







nhibition of HIV-1 entry by antibodies: potential viral and cellular targets
F Password - Journal of Internal Medicine, 2007 - Blackwell Synergy
... AIDSVAX B/B, AIDSVAX B/E, HIV gp120 vaccine – Genentech; HIV gp120 vaccine AIDSVAX –
VaxGen; HIV vaccine AIDSVAX – VaxGen. Drugs RD 2003; 4: 249–53. ...
Web Search



http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/7/2978?ck=nck
Brief Report
HIV-1 infection and pathogenesis in a novel humanized mouse model
Liguo Zhang1, Grigoriy I. Kovalev1, and Lishan Su1
1 Department of Microbiology and Immunology, The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill
The Rag2-{gamma}C double-knockout (DKO) mouse lacks T, B, and natural killer (NK) cells, and allows development of a functional human immune system with human CD34+ hematopoietic stem/progenitor cells (DKO-hu HSCs). Normal human T, B, and dendritic cells are present in peripheral blood, thymus, spleen, and lymph nodes. We report that both CCR5 and CXCR4 are expressed on




http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2796.2007.01820.x





http://bloodjournal.hematologylibrary.org/cgi/reprint/109/3/854?ck=nck
CCR5 and HIV: December 5, 2007



http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/8/3351?ck=nck
Here, we show that IDO mRNA expression is elevated in peripheral blood mononuclear cells (PBMCs) from HIV+ patients compared with uninfected healthy controls (HCs), and that in vitro inhibition of IDO with the competitive blocker 1-methyl tryptophan (1-mT) results in increased CD4+ T-cell proliferative response in PBMCs from HIV-infected patients. W

HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2, 3-dioxygenase in plasmacytoid … - all 3 versions »
A Boasso, JP Herbeuval, AW Hardy, SA Anderson, MJ … - Blood, 2007 - bloodjournal.hematologylibrary.org
... IMMUNOBIOLOGY. HIV inhibits CD4 + T-cell proliferation by inducing indoleamine
2,3-dioxygenase in plasmacytoid dendritic cells. Adriano ...


Vaccine-induced antibodies that interfere with viral entry are the protective correlate of most existing prophylactic vaccines. However, for highly variable viruses such as HIV-1, the ability to elicit broadly neutralizing antibody responses through vaccination has proven to be extremely difficult. The major targets for HIV-1 neutralizing antibodies are the viral envelope glycoprotein trimers on the surface of the virus that mediate receptor binding and entry. HIV-1 has evolved many mechanisms on the surface of envelope glycoproteins to evade antibody-mediated neutralization, including the masking of conserved regions by glycan, quaternary protein interactions and the presence of immunodominant variable elements. The primary challenge in the development of an HIV-1 vaccine that elicits broadly neutralizing antibodies therefore lies in the design of suitable envelope glycoprotein immunogens that circumvent these barriers. Here, we describe neutralizing determinants on the viral envelope glycoproteins that are defined by their function in receptor binding or by rare neutralizing antibodies isolated from HIV-infected individuals. We also describe the nonvariable cellular receptors involved in the HIV-1 entry process, or other cellular proteins, and ongoing studies to determine if antibodies against these proteins have efficacy as therapeutic reagents or, in some cases, as vaccine targets to interfere with HIV-1 entry.






this book especially page 324, 325, 326 etc
have amazing overview of viral treatments now and in the future
http://books.google.com/books?hl=en&lr=&id=lxmyfSave4IC&oi=fnd&pg=PA323&dq=Genentech+hiv+%22Genentech+%22&ots=ekP701XFug&sig=7QEvIZz9o8HU7Qd5Fr-GRyXuA-o#PPA325,M1

esp. interesting is using Ig for anti virus
and colostrum

[bimazek]

From www.bloodjournal.org by on December 5, 2007.  mRNA-rich microvesicles (MVs).

These observations3,4 also suggest that
MVs may transfer infectious particles such
as HIV and prions to other cells. They further
raise the possibility that exogenous
RNA and DNA modulate critical biologic
and pathologic responses when they are incorporatedinto
target cells. If so, then the
mechanisms that cells use for dynamic exchanges,
transfer events, and dialogs may be
even more daedal and intricate than currently
recognized, and if the specific mechanism
of stem-cell MV transfer of mRNA to
endothelial cells3 occurs in vivo, it may provide
a new pathway to angiogenesis in human
disease (see figure).

Cells use receptor-ligand interactions and endocrine, paracrine, and juxtacrine mechanisms to transmit signals to one another.
Deregibus and colleagues now report that information transfer between cells also occurs through horizontal transfer of
mRNA-rich microvesicles (MVs).
MVs are membrane blebs shed from the
surface of activated cells. Although
they were originally considered to be inert
cellular debris, it is now known that MVs
interact with cells through specific receptorligand
interactions.1 MVs also transfer receptors,
proteins, and bioactive lipids to
target cells.1 In this issue of Blood, Deregibus
and colleagues extend the functional
repertoire of MVs by showing that they are
vehicles for mRNA transport and the exchange
of genetic codes.
http://intl-bloodjournal.hematologylibrary.org/cgi/reprint/110/7/2219

From www.bloodjournal.org by on December 5, 2007.

[bimazek]

The Company is also in discussions with clinical investigators regarding the design and implementation of a second Phase 2 trial with new HspE7 in patients that are HIV-positive with low-grade CIN.

Montefiore Medical Center; William D. Kolton, M.D. of San Diego, California; Linda Roman, M.D. of the University of Southern California (USC); Michael L. Twede, M.D. of the Salt Lake Women's Center in Sandy, Utah; and Mark T. Saunders, M.D. at the Mt. Timpanogos Women's Healthcare/Physician's Research in Pleasant Grove, Utah.

http://freshnews.com/news/biotech-biomedical/article_41200.html

Nventa completes enrollment and initial dosing of second cohort in Phase 1 HspE7 safety trial
12/6/2007 @ 8:10 AM   print this article - email to a friend - join our eNewsletter
Nventa Biopharmaceuticals Corporation today announced that the Company has completed enrollment and initiated dosing of the second cohort of patients in its Phase 1 dose escalation trial examining the safety of its lead candidate, HspE7, in patients with cervical dysplasia, a precursor to cervical cancer. HspE7 is an investigational therapeutic vaccine targeting human papillomavirus (HPV)-related diseases. Patients in this cohort have received the first of three immunizations of 500 mcg of HspE7 with 500 mcg of adjuvant.
   
   In addition to safety and tolerability assessment, Nventa will also collect immunological data from these patients at the end of each cohort that may provide an early indication of potential efficacy of the compound. All patients will be typed for class I and II human leukocyte antigen (HLA) subtypes, and will be evaluated for cytokine responses, anti-HspE7 antibodies and cellular (T-cell) immunology.
   
   
   
   Affiliations and investigators in this trial currently include the Montefiore Medical Center; William D. Kolton, M.D. of San Diego, California; Linda Roman, M.D. of the University of Southern California (USC); Michael L. Twede, M.D. of the Salt Lake Women's Center in Sandy, Utah; and Mark T. Saunders, M.D. at the Mt. Timpanogos Women's Healthcare/Physician's Research in Pleasant Grove, Utah.
   
   Following successful completion of this Phase 1 trial, the Company anticipates launching a Phase 2 clinical trial with new HspE7 in patients with high-grade cervical intraepithelial neoplasia (CIN 2/3). The Company is also in discussions with clinical investigators regarding the design and implementation of a second Phase 2 trial with new HspE7 in patients that are HIV-positive with low-grade CIN.
   
   About HspE7, Lead Product Candidate:
       
   HspE7 is a novel therapeutic vaccine candidate for the treatment of diseases caused by the human papillomavirus (HPV), one of the most common sexually transmitted diseases in the world.

HspE7 is derived from Nventa's proprietary CoVal(TM) fusion platform, which uses recombinant DNA technology to covalently fuse stress proteins to target antigens, thereby stimulating cellular immune system responses. Heat shock proteins (Hsps), also known as stress proteins, are naturally present in the human body and play important roles in the immune system, including transporting substances within cells and activating cells of the immune system.
   

[Dachshund]

http://forums.poz.com/index.php?topic=17566.msg223988#msg223988

[NYCguy]

bim
the trial for the HPV pre-cancer vaccine is interesting - i just started Gardasil and have been wondering about its effectiveness on strains I or someone getting it might already have.  have you heard anything about new studies on this?

[Miss Philicia]

wow... this really *IS* "Bimazek's Research News" -- such chutzpah!

[Matty the Damned]

Tim Horn set the thread up for him Philodendron.

MtD

[Miss Philicia]

Thanks honey, I figured that out after I made that post

[Matty the Damned]

Hopefully he'll keep his toys in his playpen.

MtD

[bimazek]

 DNA vaccines have the potential to bypass inherent scientific obstacles of conventional vaccines that prevent their development for cancer and chronic infectious diseases such as HIV and hepatitis C. Pre-clinical data has indicated the ability of Inovio’s technologies to effectively deliver and significantly enhance the potency of such immunotherapies without the potential safety concerns of viral delivery systems.

Inovio Biomedical Receives Additional Milestone Payment from Merck Relating to Electroporation Delivery System for DNA Vaccines
Companies mentioned in this article:
http://freshnews.com/news/biotech-biomedical/article_41292.html

Vical
12/12/2007 @ 6:41 AM   print this article - email to a friend - join our eNewsletter
   “This is the second investigational DNA-based vaccine that Merck has advanced into clinical studies using Inovio’s proprietary electroporation delivery technology,” said Avtar Dhillon, MD, Inovio’s president and CEO. “Achievement of this milestone demonstrates Inovio’s ability to collaborate with large pharma partners to add value to their DNA-based vaccine programs.”
   
   About Inovio’s DNA Vaccine Technology
   
   DNA vaccines have the potential to bypass inherent scientific obstacles of conventional vaccines that prevent their development for cancer and chronic infectious diseases such as HIV and hepatitis C. Pre-clinical data has indicated the ability of Inovio’s technologies to effectively deliver and significantly enhance the potency of such immunotherapies without the potential safety concerns of viral delivery systems.
   
   Inovio’s DNA-based immunotherapy products consist of DNA plasmids and electroporation-based DNA delivery systems. DNA plasmids are designed to express (produce) antigens that can induce an immune response specific to a cancer or infectious disease-causing organism. These plasmids are created synthetically and readily manufactured using well-established bacterial fermentation and purification technology. After a plasmid is delivered into muscle or tumor cells, production of the desired antigens may induce a preventive or therapeutic immune response against the intended disease. Inovio’s advanced electroporation devices facilitate delivery and expression of DNA vaccines to produce the desired antigens. Non-human primate and/or interim Phase I data delivered using Inovio’s DNA delivery systems have shown significantly enhanced antibody and T-cell immune responses relative to plasmid DNA delivered by other methods, suggesting the potential to provide better preventive or therapeutic effects against complex infectious diseases and cancers.
   
   Inovio is able to deliver advanced DNA-based vaccines and immunotherapies, devices and know-how in this rapidly advancing field. The company is actively licensing its technology to pharmaceutical and biotechnology companies and supporting early stage clinical studies arising from its own research efforts or through academic collaborations.
   
   About Inovio Biomedical Corporation
   
 
Inovio Biomedical Corporation (AMEX:INO), a leader in enabling the development of DNA vaccines using electroporation-based DNA delivery, announced today it will receive a $2 million milestone payment from Merck & Co., Inc. resulting from the filing of a second Investigational New Drug application to the US Food & Drug Administration by Merck for a DNA-based vaccine using Inovio’s MedPulser® DNA Delivery System. The milestone relates to Inovio’s collaboration and license with Merck initiated in May 2004 for the development of certain DNA vaccines. Further development of the product may lead to additional milestone payments and royalties to Inovio.
   
   Inovio will receive this milestone payment for its contribution to the collaboration, which has so far demonstrated the high level of gene delivery and expression that is thought to be necessary for the induction of a therapeutic immune response. Merck has funded all clinical development costs of this candidate to date.
   

[bimazek]

http://www.sciencedaily.com/releases/2007/12/071213120945.htm
 Clark said this evidence suggests that vaccines are likely ineffective against these diseases because Lewis sequences shut down the specific immune response that enables vaccines to work.

If aggressive cancers and pathogens are using the same system of universally recognizable markers to trick the immune system into 'thinking' they're harmless, we need to determine exactly how this interaction works," Dell said. "This is where we're planning to take this research next. Understanding how these markers work at a basic biological and chemical level could lead to new ways to treat or prevent cancers and these other diseases in the future."

"This work is creating an entirely new way of thinking about how we must combat viruses like HIV and aggressive tumor cells," Clark said. "We have literally spent billions of dollars developing vaccines for AIDS and cancer. However, the latest high profile HIV and tumor vaccine trials have been spectacularly unsuccessful, perhaps for some very good reasons. We must become more clever if we are ever going to solve the problems of cancer and AIDS."

This research is being published in the Dec. 14 edition of The Journal of Biological Chemistry.

Why Vaccines Directed Against Cancer, HIV Don't Work

ScienceDaily (Dec. 13, 2007) — Researchers from the University of Missouri and Imperial College London have found evidence suggesting why vaccines directed against the virus that causes AIDS and many cancers do not work.

In research spanning more than a decade, Gary Clark, associate professor of Obstetrics, Gynecology and Women's Health in the MU School of Medicine, and Anne Dell, an investigator at Imperial College London, found that HIV, aggressive cancer cells, H. pylori, and parasitic worms known as schistosomes carry the same carbohydrate sequences as many proteins produced in human sperm.

"It's our major Achilles heel," Clark said. "Reproduction is required for the survival of our species. Therefore we are 'hard-wired' to protect our sperm and eggs as well as our unborn babies from any type of immune response. Unfortunately, our results suggest that   ...hiv-infected immune cells cause AIDS. The common thread is that each carries Lewis sequences.

[dingowarrior]

does this mean there is no hope down the pipeline?

[powerpuff]

hi Bim, I just read an article on this myself ,very interested somehow my article got moved?
they want to attach these to dialysis machines to purify in hospitals next 2 years??/. google blood cleaner 2008
aethlon medical
I hope so then one can keep healthy longer and keep the viral load down from what I understand..

[bimazek]

http://www.natmedtalk.com/showthread.php?t=1840

looks a bit balky and big
i think that dr.'s feel that the new meds, and there are 120 new amazing meds in clinical trials and pre clinical trials as well as 3 new classes of meds just approved

i think dr.s feel that this will, these meds will take care of the hiv problem for vast majority

keep posting info

http://phx.corporate-ir.net/phoenix.zhtml?c=95588&p=irol-newsArticle&ID=1077924&highlight=
seems like gp120 is a nasty protein that hurts us produced by hiv

http://phx.corporate-ir.net/phoenix.zhtml?c=95588&p=irol-newsArticle&ID=1079395&highlight=
exosomes are produced by cancer and hurt people
http://www.nature.com/bjc/journal/v92/n2/full/6602360a.html

the parallel between cancer as a disease how it hides or confuses the immune system and
hiv as a disease how it hides or confuses the immune system are more and more true

[bimazek]

This is a double whammy good breakthru
two big breakthroughs
or 273  breakthroughs plus 1 super huge one  and that one is incalculably huge...

breakthrough one...
basically they found 273 new ways to possibly attack HIV 

breakthrough two  ...
and at least one of them is so important it is the way that nature evolved a gene that is not susceptible to hiv, the famous long term non progress ors ...

rare individuals who do not progress to AIDS when they become infected with HIV.  so this is especially cool because it should be possible if not easy to find a molecule a medicine that shuts off this gene that produces a protein that HIV loves and needs and we  also know that this one in particular is not very important not very necessary because ALL long term non progressors have a mutation that removes this  gene and removes this protein

i should suppresses or squelches this gene and this protein

and these humans don't seem to need that gene or that protein very much at all


They found the gene and protein involved with that...

the famous long term non progressors ...

http://www.webmd.com/hiv-aids/news/20080110/273-new-possible-targets-for-hiv-drugs?page=2

Experts Say Finding Is Major Advance continued...

One hopeful finding is that some people carry a mutant version of one of the proteins identified by the Elledge team, apparently with no harmful consequences. This mutant version of the protein, Haynes and colleagues recently learned, is found in some of the rare individuals who do not progress to AIDS when they become infected with HIV.

"One of the critical challenges of HIV research is to learn as much about the virus as we can, as fast as possible," Haynes tells WebMD. "Studies like this have the potential to move our knowledge forward quickly, which is important given the growing worldwide epidemic of HIV and AIDS."

The findings have broad significant beyond AIDS research. They show that the same techniques can be used to dissect the workings of other viruses -- and of cancers. Elledge says his team is now looking for the Achilles' heels of cancer cells.

Elledge and colleagues report their findings in the Jan. 10 issue of the online journal Science Express.

http://news.google.com/nwshp?hl=en&tab=wn&ncl=1126137345&topic=m


..........................
along with the many new things coming out i think this is one is the one final nail, albeit 5-9 years away from now to reach the market that will give many many many if not a vast majority a long long life.

the reason also is that these genes are necessary in many other viral diseases and now science knows that for Hepatitis and many other diseases these genes must be looked at so there will be many reasons to invest....

this is the best news i have read as far as basic research in the 20 months i have been poz

there have been other great best news that are brand new approved drugs and as poz mag or another mag said in this issue 2007 is as big a break thru year as 1996 for hiv drugs

but for  basic research this is huge breakthru

my hats off to the smart and diligent scientists (i am a little shocked that this had not been done before but really it has only been 7 to 11 years that DNA RNA and human genome's sequencing existed and also the big big thing and reason why it happened now is it is only in last 1 or 2 or 3 that the cost of doing DNA RNA and human genome's sequencing fell from like five hundred million to one hundred thousand.

go it is basically happening at the right time it really could not have happened earlier

i mean geeze they had to do the DNA human genome's sequence first which they just finished a couple years ago before they could go back thru trial and error and test every gene again in a test tube one at a time to see if the proteins the gene make helped hiv grow fast.

anyway

hugs to everyone

this is a huge step forward

esp. the discovery for a gene (is it one or more than one) for non term non progressors

this is a nobel prize if you ask me

or should be.

[J220]

"One hopeful finding is that some people carry a mutant version of one of the proteins identified by the Elledge team, apparently with no harmful consequences. This mutant version of the protein, Haynes and colleagues recently learned, is found in some of the rare individuals who do not progress to AIDS when they become infected with HIV."


I have to agree with this one as being a huge discovery. If the mutant protein is in fact an independent factor needed by the virus to survive, and if the mutant virus truly causes no apparent harm to humans, this could be a very promising path for a therapeutic vaccine. Eyes on this discovery!

[bimazek]

http://news.google.com/nwshp?hl=en&tab=wn&ncl=1126137345

HIV Research Opens Up Potential Targets for Drugs
New York Times, United States - 7 hours ago
By DONALD G. McNEIL Jr. Using a new type of genetic screen, researchers at Harvard Medical School have identified 273 proteins that the AIDS virus needs to ...

"This is likely destined to be one of the best papers on HIV for this coming decade," said Robert C. Gallo, co-discoverer of the AIDS virus, who was not involved in the study. "I think it is terrific."

Gallo, who is director of the Institute of Human Virology in Baltimore, called the Harvard research "simply an elegant combination of modern molecular biology, new technology and bioinformatics that was used in a manner that has truly led somewhere."

Fauci, whose National Institutes of Health-affiliated laboratory also studies HIV's interaction with cells, said he is impressed by the strategy of selectively inhibiting cellular processes and then watching to see the effects.

"There is nothing that is completely new under the sun, but that is relatively ..." he said.

[bimazek]

"One hopeful finding is that some people carry a mutant version of one of the proteins identified by the Elledge team, apparently with no harmful consequences. This mutant version of the protein, Haynes and colleagues recently learned, is found in some of the rare individuals who do not progress to AIDS when they become infected with HIV."


I have to agree with this one as being a huge discovery. If the mutant protein is in fact an independent factor needed by the virus to survive, and if the mutant virus truly causes no apparent harm to humans, this could be a very promising path for a therapeutic vaccine. Eyes on this discovery!

in your post you say....
if the mutant virus truly causes no apparent harm to humans,

it is not
the mutant virus truly causes no apparent harm to humans,

it is a mutant human gene that causes all hiv viruses no matter what form or version or mutation to not be able to grow or change in the human who has the human gene mutation

this is very important to understand

if they can turn off this gene or suppress the protein then we all can live like

long term non progressors

[J220]

I meant mutant protein, correct. Thanks.

[bimazek]

http://money.cnn.com/news/newsfeeds/articles/marketwire/0353407.htm

this may be the first therapeutic vaccine that works, as you know the virus has a sugar coat and i guess a lipid coat that keeps the immune system from recognizing it, here they remove the lipid coat and the immune system has amazing results.... this is best vaccine results ever reported for HIV!!!  therapeutic vaccine

led to an average 15.5 times viral load reduction in the treated animals. All 6 animals in the treatment arm of the study responded with drops in viral load in excess of 90%. While the study was not powered for statistical significance, it revealed an extremely strong trend of p=0.1, indicating the strong benefit of autologous delipidated viral vaccination in lowering viral loads in chronically-infected animals.  Dr. James E.K. Hildreth commented on behalf of the study group, "The results of this study are terribly exciting and re-confirm an earlier outcome seen in a smaller group of immune-compromised animals. A viral load reduction in excess of 90%, to my knowledge, has never been seen before in other therapeutic vaccine studies. This treatment has the potential of introducing a whole new way of containing the pandemic of HIV."  Lipid Sciences' Viral Immunotherapy is a broadly applicable platform technology that focuses on the removal of the lipid coatings from lipid-enveloped viruses utilizing the Company's proprietary delipidation technologies.

ps. this is not just animal results because the model of human hiv is close to this model it is a special animal model

[bimazek]

all topics from this link...  please read full link to get more details
http://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/

Topic 1... HAART may over time help clear virus in some individuals
Tae-Wook Chun’s 10 questions you might have been afraid to ask at the 3rd Workshop on HIV Persistence During Therapy
Chun can’t find virus anywhere (including the gut), by any technique (RNA or DNA).
Is eradication possible?
Chun stated that five years ago, his answer would have been no. Now he is “cautiously optimistic in a subset of patients.” He has studied some individuals on long term ART who started relatively soon after becoming infected, and in one he can’t find virus anywhere (including the gut), by any technique (RNA or DNA). This individual has not tried stopping ART yet, however. Chun has also compared the proviral burden (amount of integrated HIV DNA) in small groups on long term ART (>7yrs) that started early vs. during chronic infection.


Topic 2... dual immunotherapeutic adjuvant/vaccination strategy may stimulate effective, long-term, immune-mediated control of persistent viral infections in humans

hopeful closing words of Brooks et al: “a similar dual immunotherapeutic adjuvant/vaccination strategy that alleviates immunosuppressive signals while boosting immunity may stimulate effective, long-term, immune-mediated control of persistent viral infections in humans, and may also be an adjuvant for primary vaccination.”

Consequently, blocking key suppressive factors could render ineffective vaccines more efficient at improving T cell immunity, and thereby allow immune-mediated control of persistent viral infection.

Souping Up Therapeutic Vaccines
Two new papers in the advance online section of the Journal of Experimental Medicine report that blocking immunosuppressive signals can give therapeutic immunization a boost. The studies follow on from work covered on the blog previously in which the IL-10/IL-10 receptor and PD-1/PD-L1 signaling pathways were identified as key contributors to viral persistence in the mouse model of chronic infection with lymphocytic choriomeningitis virus (LCMV).   
In the first paper, David Brooks and colleagues from Mike Oldstone’s laboratory at Scripps show that combining DNA vaccination with an antibody blocking the IL-10 receptor leads to improved LCMV-specific CD4 and CD8 T cell function and accelerated clearance of the virus from chronically infected mice. In the second paper, Sang-Jun Ha and a team from Rafi Ahmed’s lab at Emory University report that immunization with a vaccinia vector encoding a single CD8 T cell epitope from LCMV also accelerates viral clearance when combined with an antibody blocking PD-L1 (the ligand for the molecule PD-1). The vaccine had no effect when given alone. In addition, these researchers demonstrate an effect of the vaccine plus PD-L1 blockade in mice transiently depleted of CD4 T cells, suggesting that the approach might have an impact in settings of CD4 T cell deficiency.
Both groups conclude by citing each other’s work and noting that, taken together, the results indicate that immunosuppressive signaling in chronic infection may explain the disappointing results of most therapeutic vaccination studies conducted to date. The authors also argue that their data point toward new strategies for boosting the impact of therapeutic immunization. In the hopeful closing words of Brooks et al: “a similar dual immunotherapeutic adjuvant/vaccination strategy that alleviates immunosuppressive signals while boosting immunity may stimulate effective, long-term, immune-mediated control of persistent viral infections in humans, and may also be an adjuvant for primary vaccination.”
The Journal of Experimental Medicine
Published online 10 March 2008
doi:10.1084/jem.20071948







 Topic 3-- immunologist Mark Connors. Over the years, Connors has studied HIV-specific immune responses and authored many articles reported in the literature. In 2002, however, he identified HIV-specific CD8 T cell proliferation as a potentially important correlate, a finding several other research groups have now confirmed. At the summit, he cited additional assays his lab is working on, and expressed confidence that robust and broadly applicable correlates of immunological control are within striking distance. Furthermore, he also cited the fact that several Merck vaccine recipients who became infected in the STEP trial and carry the favorable immune response gene HLA B*57 are controlling their viral loads to undetectable levels. Initially, this was assumed to be an HLA B*57 effect but Connors argued that the frequency of the occurrence is far higher than would be anticipated in the absence of immunization, suggesting that it reflects an interaction between the vaccine and the favorable HLA allele akin to that seen in Merck’s now notorious SIV challenge studies, in which only immunized macaques bearing the Mamu A*01 allele (the B*57 equivalent) showed significant viral load reductions. The implication is that while the Merck vaccine was far from optimal, it may have been able to enhance the HLA B*57 effect. If this finding actually holds up, it may offer additional validation of the SIV/macaque model and it would also strengthen the argument for developing improved immunogens with the potential to achieve this outcome in people lacking HLA B*57.




 
 Topic 4  Genetic Associations with Control of HIV Replication

HCP5 might somehow have a direct anti-HIV effect
 
 HCP5 is also an endogenous retroviral element (a part of the human genome derived from an ancient retroviral infection which gained access the human germ line by infecting an egg or sperm cell) and so Goldstein initially speculated that the SNP in HCP5 might somehow have a direct anti-HIV effect. At CROI, he reported that studies in which the SNP-containing version of HCP5 was overexpressed in cells showed no inhibition of HIV replication, suggesting that the SNP is mediating its effect via other means (exactly how is under investigation).
 
Genetic Associations with Control of HIV Replication
At the recent CROI meeting, David Goldstein from Duke University gave a plenary presentation on genetic determinants of viral load set point in HIV-infected individuals.  Their approach involved analyzing a staggering 500,000 different single nucleotide polymorphisms (SNPs) present in the human genome to see if they were associated with lower viral load set points . . The first was a SNP in a gene called HCP5. This is linked to an immune response gene called HLA B*5701 which is well known to be over-represented among HIV-infected long-term non-progressors (HLA B*5701 makes a receptor on CD8 T cells which appears particularly good at recognizing HIV epitopes). However, HCP5 is also an endogenous retroviral element (a part of the human genome derived from an ancient retroviral infection which gained access the human germ line by infecting an egg or sperm cell) and so Goldstein initially speculated that the SNP in HCP5 might somehow have a direct anti-HIV effect. But because HIV’s Nef protein is known to cause a reduction in HLA-B molecules on infected cells (as a means of escaping the immune response), Goldstein’s hypothesis is that the SNP he has identified causes more HLA-C molecules to be expressed, thereby making it easier for CD8 T cells to identify HIV-infected cells. He is currently collaborating with Andrew McMichael at Oxford University to measure the effect of the SNP on HLA-C expression.

To give a sense of how a combination of genetic factors can have a profound impact on HIV disease progression, Goldstein showed an analysis that included the SNPs in the HCP5, HLA-C, and ZNRD1/RNF39 genes and two other known favorable genetic polymorphisms in CCR5 and CCR2 genes (CCR5Δ32 and CCR2 V64I). HIV-infected individuals with no favorable mutations in any of these genes showed an average time of less than two years from infection to a CD4 T cell count of less than 350. In contrast, people with one or two favorable mutations in at least four of these genes did not experience a CD4 T cell decline to this level for an average period of more than eight years.

Goldstein’s group is now embarking on an effort to uncover genetic associations with the magnitude of antibody responses generated against a vaccine, using data from the North American efficacy trial of AIDSVAX. This is a potentially important area of study because the ability of an individual to generate a high titer antibody response was correlated with reduced susceptibility to HIV infection in the trial cohort. Some researchers have suggested an analogy with the association between the magnitude of anti-Ad5 antibody responses and susceptibility to HIV infection seen in the placebo group of the recent Merck vaccine trial, so Goldstein’s work may have the potential shed light on that mystery also. Another important area of ongoing study mentioned by Goldstein is an analysis of genetic associations with viral load set point restricted to African American individuals.

[Matty the Damned]

You already have a thread for this stuff

MtD

[Ann]

Bim,

I merged your threads. Don't keep starting new ones, OK? Thanks.

Ann

[bimazek]

Summit on HIV Vaccine Research and Development
was recently held and researchers from all over world met

http://www.macrovolt.com/live/dgi_032508/

I have just spent good parts of the last 3 days watching this video broadcast of the top world vaccine specialists researchers for hiv it is over 6.5 hours long  and sometimes i had to go over what someone said 2 times to fully absorb all the complicated stuff

basically there is much to report here

obviously the news mis reported some of it

but the big things are

there is not enough money for any of the HIV vaccine research even with the big gates grant, that even the primate labs in new england are having trouble paying
heating bills because of the high costs of fuel, that the congress is not putting up enough money and there is a vast vast undersupply of money on this problem
this was shocking to me because i thought there was enough money in preventative and therapudic vaccine research so perhaps activism can help

other topics
they have a very very good animal model which is almost exactly similar to human hiv to test any new vaccine ideas but it is expensive to keep breed the animals, but human trials are only way to truly see if a new idea for vaccine will really work even though animal models are very good

at the hour of 5:06 the video  made me cry and tear up when the emory director said that he and his staff personally called all 130 vollenteers to tell them of the merck failure
and the vollenteers said universally, "when can we vollenteer again to help" -- imagine the scientists called to tell them that some vollenteers were made more susseptable
and these wonderful selfless individuals want to help all of mankind and want to vollenteer again even in the face of the risks  i am still choacked up just reading this above

other things said in the 5 hour summit

the guy who invented the malaria vaccine, the cholera vaccine and many others had interesting things to say about how hiv is yes different and harder but not that much different and not that much harder and that it is still possible to make the vaccine and hey malaria vaccine, the cholera vaccine was hard to figure out too

there is not enough money to keep the young new researchers in the field

that if you treat someone with HAART within the first days of infection then give a vaccine this was something unique therapudically

that many many new ideas and parts of the virus and new basic science needs to be learned

that no scientist really know exactly how ANY existing vaccine works exactly for any disease so they need to study this in detail in the immune system,

that they are getting close or at least there is many new avenues and ways to design a vaccine that needed to be tested in humans asap

that there is lots of vollenteers so human vollenteers are not a problem

that well many many detailed scientific ideas and explainations that you have to watch the whole thing to see it, but basically there are lots of ways to deliver parts of the hiv coat envelope, proteins, insides, etc and also many new ways to stimulate the immune system in many different ways that need to be invented and thought of and tried

that perhaps soneone could still just stubble upon an idea or a solution and wow suddenly we would have a vaccine for hiv and it may come from many areas of research not just pure hiv research

that bruce walker at harvard is a genius because he is looking at early infection and also at elite controllers but even he had to go to private money sources to fund what seems to me so obvious -- figure out how the elite controllers immune system controls infection without meds and replicate it

that even harvard isn't helping enough with money for hiv research if they have a 92 billion endowment and one of their top researchers had to go begging to get money to study this... my opinion ... if you went to harvard, yale, emory, or UC or any big medical research university try to get involved and see if more money can be put into hiv research please

that many brilliant people all of usa and world are workign very very hard but all the easy things for vaccines for hiv have been tried and all have failed

that there are a few very great giants minds in the field and they are like gods with thier discoveries and ideas and research,

that there is so so so much that the science does not understand about how hiv hurts the immune system and also how the immune system works itself

that science must come up with many new vaccine ideas and then has to select only the best ideas for trials in animals and then people

that smaller trials are better and faster with smaller groups of people

i strongly oppose the AHF in their call for slowing hiv vaccine trials that was a big mistake

many new dev. in hiv vaccine research two papers in euro vac dna prime -- many promising signs

there was a difference in protection with a vaccine in protecting circumsized and uncircumsized men

prime boosted vaccines using many different vectors to insert the genetic material

cultivate the new young investigators

come up with new ideas   

primate models quite good according to gallo

one hurdle to vaccines is science must maintain antibody response continually for first many weeks, but they cant figure out how to do that -- i personally never understood why giving same vaccine 5 times would not help with that question

someplace called OTC talked about by gallo has billions of dollars and a rotating chairmanship sometimes to family memeber and he felt they should put more money into vaccine research

us army is doing hiv vaccine research according to gallo

they have vaccines that reduce somewhat viral load but it does not last but that it increases survival so that they are getting closer

one guy said we are not there and we are not close we need lots of basic science to figure out how to make a vaccine
discovery innovation

we need to be evolutionists... what can we learn from primates who get siv but live with it with out getting sick he said
we will not stop hiv vaccine research even though ahf asked us to stop, not only will we not stop it we will not even consider stopping, not only will we not stop we will try to increase the budget for it wherever possible

there is competition between research institutes, universities, private biotech companies, us army, and other usa and intl orgs all working on vaccine research and many called on coordinated efforts and more disclosure of who is working on what so that a new solution to vaccine is found faster safer and all agreed they must work leaner and with tight budgets

[bimazek]

Giant new discovery
see DIAGRAM HERE
http://tagbasicscienceproject.typepad.com/.shared/image.html?/photos/uncategorized/2008/01/10/brassimage.jpg

Giant new discovery I have been wanting to post this but have been out of town 4 months.

Probing HIV's Dependence Factors on Host cell Proteins

in my opinion, This is, (and I have been following HIV research and knowledge for 27 years since an MD/PhD/Vet researcher told me in 1981 that this new disease was caused by retrovirus just like in cats, he was one of first in world to guess this... )   in my opinion, This is.... drum roll

... this new discovery is the largest most important discovery in the history of any disease and in the history of HIV research. I believe.  I hope the editors of this site will give it the attention it deserves.  No other time in history has siRNA genetic analysis (which is brand new tool) used to find ALL the genes and proteins that a disease uses.

Never before has it been possible to see every gene and every protein that a disease process uses.  This came about because of the love and hard work of clinical scientists who work with real people who have hiv.

The most exciting and important discovery is the diagram of all 273 genes and proteins that HIV hijacks to reproduce itself.  See above diagram.  This is it, there is no other genes or proteins they tested EVERY single human gene to see if hiv needed it to replicate.

This diagram represents one CD4 cell.  This shows the actual paths and life cycle of HIV.   The amazing part is that the part that is in GREEN was all that science knew before this discovery by HARVARD.  EVERYTHING ELSE that is not green is new.

BTW all the present hiv meds work on only the pathways of the GREEN genes. 

All the other proteins and genes that HIV hiJACKS in red or black paths or blue are NEW and never known before.

How they found all these is a miracle of new research techniques and they now know more about hiv life in a cell than any disease in the history of the world.  Harvard and bruce walker are the geniuses behind all this and they will most definately deserve and win the nobel prize for this in my humble opinion. 

What this means is that meds can be designed to dail down to lower the expression of one or more of these genes just like protease inhibitors or Nukes or non nukes reduce a cell process and thus halt hiv

but it is even more exciting because science believes that some of these genes can be reduced say twenty percent and this will turn off completely the production of HIV but not turn off the CD4 cell itself.

So that is exciting.  How they did it..

"The researchers used an approach that involves blocking the activity of known human genes using small slices of RNA called small interfering RNAs (siRNAs). A staggering 21,121 pools of four siRNAs per gene were employed in the study, ultimately revealing 273 host proteins necessary for efficient HIV replication (the researchers have dubbed them "HIV dependency factors" or HDFs).  Thirty-six HDFs comprise previously reported factors such as the CD4 and CXCR4 proteins.  One identified protein, ZNRD1, was also implicated in a recent study of genomic associations with viral load set point in people with HIV (mutations in the gene for ZNRD1 were associated with slow progression) So much data was generated that much of it is not in the paper but in the supplemental online material that accompanies it. The authors also offer a schematic that gives a sense of the complex theater of virus-host interactions.."

supplemental online material --- i read this material it or skimmed it and it is incredible, and is tens of hundreds of pages of exactly what each of these genes does in the cell and the body it is complete, many of these genes science does not even know what they do in humans but they included the same gene and they knew what the gene does in other species

this is the diagram of the CD4 cell, first notice the famous green paths, all green is what was already known about hiv

notice the cd4 receptor at the top, follow the green line down into the cell into the nucleus,

notice transcription and integration -- this is the part that we all learn when we take a hiv meds for beginners class  -- where the nukes and non nukes work, i cant find the protease enzyme on here but it must be there somewhere does anyone know the gene name for protease enzyme

HDFs stands for HIV Dependence Factors which are proteins or genes basically

remember that everything that is red, blue or black is new info new discoveries only weeks old

everyone of these can be target of new meds, new gene therapies or new vaccines.
http://tagbasicscienceproject.typepad.com/.shared/image.html?/photos/uncategorized/2008/01/10/brassimage.jpg
see this diagram and study it

if you have any question please post it here.

here is some more reports on this discovery in press
http://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2008/01/probing-hivs-de.html

http://www.google.com/search?hl=en&q=+hiv+dependency+factors&btnG=Search

http://www.citeulike.org/user/zwang/article/2219289

http://www.health24.com/news/HIV_AIDS/1-920,43677.asp

http://sbaminbeta.blogspot.com/2008/01/hope-survives-hiv-dependency-factors.html

[J220]

wow that is amazing data....great post.

[Magnus]

Good News- The sooner this translates into new drugs & gene therapies the better!

[ronaldinho]

Giant new discovery
see DIAGRAM HERE
http://tagbasicscienceproject.typepad.com/.shared/image.html?/photos/uncategorized/2008/01/10/brassimage.jpg

Giant new discovery I have been wanting to post this but have been out of town 4 months.

Probing HIV's Dependence Factors on Host cell Proteins

in my opinion, This is, (and I have been following HIV research and knowledge for 27 years since an MD/PhD/Vet researcher told me in 1981 that this new disease was caused by retrovirus just like in cats, he was one of first in world to guess this... )   in my opinion, This is.... drum roll

I think there is a specific thread that discussed this same subject some time ago:

http://forums.poz.com/index.php?topic=18308.0

[bimazek]

The practical application of this experiment is clear and crucial: A method to prevent HIV/AIDS could be devised from these findings.   Infecting a person with measles is out of the question, but a new type of vaccine could be created that would give immunity to measles as well as HIV.  The researchers are already well underway with further research, exploring other interactions of the HIV virus.
Measles virus slows progression of HIV infection
http://media.www.jhunewsletter.com/media/storage/paper932/news/2008/04/03/Science/Measles.Virus.Slows.Progression.Of.Hiv.Infection-3301387-page2.shtml

4-4-08

Scientists are using the world's most powerful computer to design drugs that could prevent HIV infection.
http://ukpress.google.com/article/ALeqM5hIMe8w-LeXTvfVaFYH-1DF-jNdJw
Jason Crain, IBM professor of physics at the University of Edinburgh, said: "The idea is to try and inhibit infection by the HIV virus rather than treat already infected cells so one of the strategies for doing that is to design molecules that will attach to the important parts of the virus and inhibit the initial viral fusion events.

[bimazek]

I did a search on all new hiv papers in 2008.  There are 5000 so far.  These dozen stood out when i reviewed the first 500 abstracts.   2008 science papers on hiv

http://scholar.google.com/scholar?q=hiv&num=100&hl=en&lr=&as_ylo=2008&as_yhi=2008&as_subj=med&start=300&sa=N

HAART lowers Viral Burden in the Lungs
Effect of Highly Active Antiretroviral Therapy on Viral Burden in the Lungs of HIV-Infected Subjects
http://www.journals.uchicago.edu/doi/abs/10.1086/523766
Conclusion.  HAART is associated with a significant decrease in the pulmonary HIV burden and a return of alveolar cellular constituents to normal.  Background.  Human immunodeficiency virus (HIV) is readily detectable in the lungs of infected subjects and leads to an accumulation of CD8+ lymphocytes in the alveolar space. Although highly active antiretroviral therapy (HAART) is effective in reducing viremia, less is known about its effect on tissue compartments. The AIDS Clinical Trials Group Protocol 723 Team evaluated the effect of HAART on lung viral load and cellular constituents.
Journal of Infectious Diseases 2008;197:109–116
© 2008 by the Infectious Diseases Society of America. All rights reserved.
MAJOR ARTICLE

 2008 Jan;180(1):21-9. Epub 2007 Nov 16.Click here to read Links
Magnetic resonance imaging findings of the brain in adult HIV and AIDS patients]
http://www.ncbi.nlm.nih.gov/pubmed/18008191


ascorbic Acid: Biologic Functions and
Relation to hiv
http://jnci.oxfordjournals.org/cgi/content/citation/83/8/547
The effect of ascorbate on human immunodeficiency virus
(HIV) replication was described by Dr Raxit Jariwalla (Linus
Pauling Institute, Palo Alto, Calif). In chronically infected T
lymphocytes exposed to high but nontoxic levels of sodium as-
corbate, reverse transcriptase activity was reduced by more than
99%. Levels of p24 HIV core antigen in the culture supernatant
were reduced by 90%. In acutely infected cells, ascorbate
reduced syncytium formation by 93%. The continuous presence
of ascorbate was necessary for HIV suppression. Ascorbate did
not inactivate extracellular virus. Under the same conditions,
there were no detectable inhibitory effects of ascorbate on
growth, metabolic activity, or rate of protein synthesis in unin-
fected T lymphocytes.


Future HIV Therapy
March 2008, Vol. 2, No. 2, Pages 99-104
(doi:10.2217/17469600.2.2.99)
http://www.futuremedicine.com/doi/abs/10.2217/17469600.2.2.99
Challenges facing the US HIV/AIDS medical care system

Journal of Infectious Diseases 2008;197:S34–S7
© 2008 by the Infectious Diseases Society of America. All rights reserved.
Stigma in the Time of Influenza: Social and Institutional Responses to Pandemic Emergencies
http://www.journals.uchicago.edu/doi/abs/10.1086/524986
Ron Barrett1 andPeter J. Brown2 1School of Nursing and 2Department of Anthropology, Emory University, Atlanta, Georgia

http://www.ncbi.nlm.nih.gov/pubmed/18190281
No patient was receiving highly active antiretroviral therapy before presentation with PCP, and none began highly active antiretroviral therapy during treatment of PCP. CONCLUSIONS: Mortality risk factors for PCP were identifiable at or soon after hospitalization. The trend towards improved outcome after June 1996 occurred in the absence of highly active antiretroviral therapy.  BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) remains the leading cause of opportunistic infection among human immunodeficiency virus (HIV)-infected persons.

 Apoptosis and HIV Infection: About Molecules and Genes
http://www.ingentaconnect.com/content/ben/cpd/2008/00000014/00000003/art00005  Abstract:
During the evolution, the immune system has developed several strategies to fight viral infections. Apoptosis, autophagy and necrosis are different types of cell death that play a main role in the interactions between infective agents and the host, since they are often important defence mechanisms that have to avoid the spreading of the infection. In turn, viruses have evolved numerous ways to evade the host immune system by influencing the behaviour and functionality of several components. HIV infects and kills CD4+ T helper lymphocytes, preferentially those that are antigen-specific, but also encodes proteins with apoptotic capacities, including gp120, gp160, Tat, Nef, Vpr, Vpu, Vif and, last but not least, the viral protease. This latter protein can kill infected and uninfected lymphocytes through the action of several host molecules, mainly members of the tumor necrosis factor family, or via the mitochondrial apoptotic pathway. The proinflammatory state that is characteristic of both the acute and chronic phase of HIV infection facilitates cell death, and is an additional cause of immune damage.  Potent antiretroviral drugs that are largely use in therapy can reduce apoptosis by different mechanisms, that not only include the diminished production of the virus by infected cells and the subsequent reduction of inflammation, but also a direct action on the viral protease. The role of the host genetic background is finally crucial in understanding the process of cell death in HIV infection.

study of those terrible times before haart...
when there was no treatment  http://aje.oxfordjournals.org/cgi/content/abstract/140/8/747
The median time from HIV seroconversion to AIDS was 8.3 years, that from HIV serocon version to death was 8.9 years, and that from AIDS to death was 17 months. The authors evaluated HIV disease progression with respect to demographic, clinical, and behavioral cofactors. Younger age and use of prophylaxis against Pneumocystis carinii pneumonia were significantly related to slower progression from seroconversion to death.


Can the New Humanized Mouse Model Give HIV Research a Boost?
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pmed.0050013&ct=1
Barbara L. Shacklett  From the perspective of a basic scientist searching for improved animal models in which to study human disease, the present study represents a clear advance in the field. However, given the uncertainties that remain, the BLT mouse is unlikely to replace the SIV model for studying pathogenesis and transmission. At this stage, the most prudent approach is to consider the new humanized rodents and the more established, nonhuman primate models as complementary systems, both of which can yield useful information but neither of which is infallible.  Infection of rhesus macaques with simian immunodeficiency virus (SIV) has provided an excellent nonhuman primate model for studying HIV pathogenesis (reviewed in [3]). SIV is closely related to HIV on a molecular level, its replication may be inhibited by many of the same antiretroviral compounds, and it induces an acquired immunodeficiency syndrome (AIDS) that mimics human AIDS in many important respects.

Physiologic growth hormone (GH) replacement appears to be beneficial in patients with HIV-associated …
I Weekly - Inpharma Weekly, 2008 - inpharma.adisonline.com
... Physiologic growth hormone (GH) replacement appears to be beneficial in patients
with HIV-associated lipodystrophy,.

What is the risk of mortality following diagnosis of multidrug-resistant HIV-1?
D Grover, A Copas, H Green, SG Edwards, DT Dunn, C … - Journal of Antimicrobial Chemotherapy, 2008 - Br Soc Antimicrob Chemo http://jac.oxfordjournals.org/cgi/content/abstract/61/3/705... What is the risk of mortality following diagnosis of multidrug-resistant HIV-1?


Blood and Guts and HIV: Preferential HIV Persistence in GI Mucosa.
S Yukl, JK Wong - J Infect Dis, 2008 - ncbi.nlm.nih.gov
J Infect Dis. 2008 Feb 8; [Epub ahead of print], Blood and Guts and HIV:
Preferential HIV Persistence in GI Mucosa. Yukl S, Wong JK. http://www.ncbi.nlm.nih.gov/pubmed/18260765


What is the risk of mortality following diagnosis of multidrug-resistant HIV-1?
D Grover, A Copas, H Green, SG Edwards, DT Dunn, C … - Journal of Antimicrobial Chemotherapy, 2008 - Br Soc Antimicrob Chemo ... What is the risk of mortality following diagnosis of multidrug-resistant HIV-1? ... Keywords:
MDR HIV-1 , genotypic sensitivity score , antiretroviral therapy. .  http://jac.oxfordjournals.org/cgi/content/abstract/61/3/705
MDR HIV-1 , genotypic sensitivity score , antiretroviral therapy. ...