News (Updated June 6, 2010)

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Structure of immune molecule that counteracts HIV strains determined  

ANI Wednesday, June 2, 2010 19:39  

A team led by Scripps Research Institute scientists has determined the structure of an immune system antibody molecule that effectively acts against most strains of human immunodeficiency virus (HIV), the virus that causes AIDS.

Published in an advance, online issue of the journal Proceedings of the National Academy of Sciences (PNAS) during the week of June 1, 2010, the study illuminates an unusual human antibody called PG16.

"This study advances the overall goal of how to design an HIV vaccine," said Scripps Research Professor Ian Wilson, who led the team with Dennis Burton, Scripps Research professor and scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center at Scripps Research. "This antibody is highly effective in neutralizing HIV-1 and has evolved novel features to combat the virus."

According to the World Health Organization's latest statistics, around 33 million people are living with HIV worldwide. During 2008 alone, more than 2 million men, women, and children succumbed to the disease and an estimated 2.7 million were infected with HIV.

One of the most compelling medical challenges today is to develop a vaccine that will provide complete protection to someone who is later exposed to this virus.

HIV causes AIDS by binding to, entering, and ultimately leading to the death of T helper cells, which are immune cells that are necessary to fight off infections by common bacteria and other pathogens. As HIV depletes the body of T helper cells, common pathogens can become potentially lethal.

An effective HIV vaccine would induce antibodies (specialized immune system molecules) against the virus prior to exposure to the virus. Also called immunoglobulins, these antibodies would circulate through the blood, and track down and kill the virus.

 

State cutbacks prompt Gilead to cut HIV prices

June 4, 2010 By Tracy Staton

Call it another trickle-down effect of the Great Recession. Gilead Sciences  says it's launching new discounts and an extended pricing freeze on its HIV meds to combat budget shortfalls in AIDS assistance programs across the country.

As of last month, there were more than 1,100 patients on AIDS assistance waiting lists in 10 states--and those lists have grown by a factor of 10 over the past year, according to the San Jose Business Journal. Just 99 individuals stood in the same queue in May 2009. Plus, 16 states have tightened access to drug-purchasing assistance by cutting drugs from their formularies, limiting spending on AIDS meds, and tightening up eligibility based on income.

So here's what Gilead 's doing: Additional discounts on Truvada, Viread and Emtriva for those assistance programs, plus an extended price freeze on those drugs, for one thing. For another, Gilead is expanding its own assistance program to make more patients eligible for help. 

Several drugmakers have expanded their patient assistance programs in the face of economic woes around the world. Pfizer, for one, instituted a "free meds" program for those who've lost their jobs. GlaxoSmithKline has offered free vaccines to uninsured patients, and it's giving 50 percent discounts to patients who don't have prescription drug coverage.

HIV vaccine — keeping hope alive

05 June 2010

IT took 105 years for researchers to develop a vaccine against the deadly typhoid disease and 89 to get one against polio.
This is what Mitchell Warren, the executive director of the AIDS Vaccine Advocacy Coalition (AVAC) often tells anxious prevention advocates seeking answers to why it has taken so long to come up with an HIV vaccine.


She has always been an optimist in the face of adversity.
“For years now researchers and scientists have been working hard to develop an HIV vaccine but this is a very involving process, it takes years of hard work, disappointments and starting all over again but we will eventually get there,” Warren told journalists at the just-ended International Microbicides Conference in Pittsburgh , US .


“When you look at other diseases and the time between discovery of microbiologic cause of that disease and development of the vaccine you can see that a vaccine cannot be developed overnight otherwise you will have a product on the market that will do more harm than good for people.


“There are numerous checks and balances, we all have to be patient but while scientists and researchers develop a vaccine those living with HIV must be given the right care and treatment.”
For the first time, this year the world commemorated HIV Vaccine Awareness Day on May 18 which came at a time results from clinical trials have shown that an Aids vaccine is possible.
The evidence came from the world’s largest vaccine trial that was conducted in Thailand and ended last year in September.


The results showed that an experimental Aids vaccine could lower the risk of HIV infection by about 30%.
Although not enough to allow for registration of the vaccine, Warren says there is greater cause for hope than ever before and a renewed sense of urgency to transform this hope into a reality.
“Despite the many perspectives on and interpretations of the trial — and its results — the Thai Aids vaccine trial provides evidence for the first time that it is possible to reduce the risk of HIV infection with a vaccine,” said Warren .


“In fact, there’s renewed energy in the Aids vaccine field today, even as we grapple with what these results mean and where we go from here.
“The next steps for the field must involve more not less: more trials, more community volunteerism, more political will and sustained funding.


“One way to help ensure this is to celebrate what has happened to date, even as we prepare for everything that still needs to be done.”
Zimbabwe AVAC/Global Campaign for Microbicides prevention research fellow Munyaradzi Chimwara agreed that there is need for more funding for the field of prevention research such as the development of a vaccine and microbicides.


“It may appear as though we are running out of time in developing an HIV vaccine or microbicides that work but if we look at how research is done, it is very taxing and there are checks and balances that are meant to protect you and me,” said Chimwara.


“When you look at the time frames of the development of vaccines you can see that the shortest took 23 years while the longest over a century, so HIV research is very demanding.


“Sometimes even after taking that long results may not be encouraging but donors and funders should not tire because developing a vaccine or microbicide will in the long run cut down money spent on HIV prevention and treatment.”


Founded in 1995, AVAC is an international non-profit organisation that uses education, policy analysis, advocacy, and community mobilisation to accelerate the ethical development and eventual global delivery of Aids vaccines and other new HIV prevention options as part of a comprehensive response to the pandemic.

BY BERTHA SHOKO

 

New drug delivery systems to combat HIV

Jun 1, 2010

NEW DELHI : The HIV virus is unique and requires equally novel interventions. Scientists are, therefore, working on various out-of-the-box drug delivery systems to protect women against HIV.

Imagine a cellotape-like film that once inserted in the vagina would melt away and disperse drug to cells to protect against HIV. Or maybe a flexible vaginal ring containing two anti-HIV drugs. How about an almond-shaped vaginal tablet that would dissolve and deliver sustained levels of anti-HIV drugs over several hours.

All these products have now passed initial trials, according to scientists who presented their early findings at the International Microbicides Conference in Pittsburgh over the weekend.

Most of the world's women do not control when, with whom and with what protection, if any, they have sexual relations. This powerlessness is most acute in developing countries where HIV prevalence is highest. Women's most urgent need is for a prevention technology which they control themselves.

In the absence of a vaccine against HIV, microbicides are the answer — chemical agents used typically by women within the vagina in order to prevent infection by HIV.

However, most of the research on microbicides till now has focused on gels or vaginal creams. But the world has failed to create a successful microbicide. In February 2007, trials of a cellulose sulphate called Ushercell was stopped ahead of schedule for failing to work. In 2008, Carraguard, a vaginal cream that was the first to make it through late-stage testing, failed. It was unable to prevent transmission of the virus.

 

Fat loss caused by some anti-HIV drugs persists in the long term

Michael Carter, May 31, 2010

The fat loss that can be caused by some anti-HIV drugs appears to persist in the long term despite discontinuation of the drugs that cause it, US investigators report in a study published in the online edition of AIDS.

Researchers from the prospective Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study found that significant differences in fat distribution were evident between HIV-positive patients and HIV-negative controls and persisted over the five years of the study.

Stopping d4T (stavudine, Zerit), the anti-HIV drug most associated with fat loss, was associated with only modest gains in limb fat.

Soon after it was introduced, combination antiretroviral therapy became associated with changes in body-fat distribution and metabolic alterations associated with a long-term risk of cardiovascular disease. This syndrome of side-effects is called lipodystrophy.

Fat gain around the abdomen (visceral adiposity) and fat loss from the limbs and face (lipoatrophy) were observed in some patients. Protease inhibitors were originally thought to be the cause, but it became apparent that a major cause of fat loss was the mitochondrial toxicity caused by some nucleoside reverse transcriptase inhibitors (NRTIs), especially d4T, and – to a lesser extent – AZT (zidovudine, Retrovir, also in the combination pills Combivir and Trizivir).

Stopping or changing HIV treatment became an established strategy for treating lipodystrophy.

A lot of research has been undertaken in lipodystrophy, one of the major projects being the FRAM study.

In this study, investigators used MRI scans to compare the body-fat distribution of HIV-positive patients and HIV-negative controls. Their initial analysis found that patients with HIV had significantly lower levels of subcutaneous fat than their HIV-negative peers.

The investigators wished to see if these differences persisted in the long term. They therefore repeated their analysis after five years of follow-up.

Their study population included 477 HIV-positive patients and 211 HIV-negative controls. Their characteristics were well matched; however, the HIV-positive patients were more likely to be male (68% vs 53%).

In the first analysis, and then five years later, the HIV-positive patients had significantly lower levels of fat in all the body areas which were measured.

The investigators found that those with HIV were more likely than the controls to lose both subcutaneous fat (35% vs 27%, p = 0.0013) and visceral fat (17% vs 5%, p < 0.0001).

At baseline, 48% of HIV-positive patients had fat loss, and this had increased to 53% after five years.

Of the HIV-positive patients diagnosed with lipoatrophy at baseline, 82% still had fat loss five years later.

The baseline analysis showed that the mean limb-fat level of HIV-positive men was 67% of that seen in the controls. This difference persisted in the long term, with HIV-positive men having only two-thirds (65%) of the limb fat seen in their HIV-negative peers.

Limb-fat levels were also lower in HIV-positive women at both the initial assessment and at follow-up (83% and 77%).

Discontinuing treatment with d4T, the drug most associated with fat loss, had little long-term impact on limb-fat gain. Patients who adopted this strategy experienced an average annual increase of fat in the leg of only 1%. “Likewise”, write the investigators, “little gain was associated with discontinuation of AZT or other antiretroviral drugs.”

The investigators conclude that “there is no relative recovery from lipoatrophy when HIV-infected participants are compared to controls.”

They add, “these data must be considered when studying the potential mechanisms underlying HIV-associated lipodystrophy. It remains to be determined whether there was destruction of adipose cells and precursors…or whether other factors continue to contribute to the persistence of lipoatrophy in HIV infection.”

Reference
Grunfeld C et al. Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy. AIDS 24: online edition, DOI: 10. 1097/QAD.0b013e32833ac7a2, 2010.

A patient who tested positive for extreme drug resistant tuberculosis (XDR-TB) awaits treatment at a rural hospital at Tugela Ferry in South Africa 's impoverished KwaZulu Natal province, October 28, 2006.

Credit: Reuters/Mike Hutchings


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