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Published online 21 October 2009 | Nature | doi:10.1038/news.2009.1035

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HIV vaccine trial under fire

Expert scrutiny casts doubt on 'historic' results.

Declan Butler

Are hopes for an HIV vaccine as distant as ever?Getty

The sponsors of the largest ever HIV vaccine trial yesterday hailed a "historic" moment as they formally announced the trial's results at an international AIDS vaccine meeting in Paris . The results received rapturous applause from an audience of more than 1,000 HIV researchers.

But some scientists are much more sceptical of the findings, arguing that the response of the HIV research community, long deprived of any good news from vaccine trials, is based more on hope than on rigorous science.

The US$119-million phase III trial, sponsored by the health ministry of Thailand and the US Army, started in Thailand in 2003. It enrolled 16,402 people, who were split evenly into a control group and a vaccine group. People in the vaccine group were given four shots of ALVAC-HIV, an attenuated canarypox virus carrying HIV genes, and two shots of AIDSVAX, a recombinant form of the gp120 HIV surface protein.

The trial's results were published on 20 October, to coincide with the meeting, in the New England Journal of Medicine1. Researchers have been impatient to see the full data since the team announced on 24 September that the treatment had cut the the risk of HIV infection by nearly one-third (see Vaccine protects against HIV virus). The results are a "milestone in HIV vaccine research", says Supachai Rerks-Ngarm, the paper's first author, and a researcher at the Thai Ministry of Public Health.

"Because the history of preventive interventions against HIV has been so poor, the HIV research community has seized upon this," says Peter Smith, a tropical epidemiologist at the London School of Hygiene and Tropical Medicine, and an expert on statistics. "But at most it is a glimmer of hope. There is not much evidence from the data that it protects at all."

Data crunch

The trial was set up to measure the number of people in each group who became infected with HIV, and the amount of the virus that was circulating in the blood (the viral load) of those who became infected during the trial.

“At most it is a glimmer of hope”

Peter Smith
London School
of Hygiene and Tropical Medicine

The teams analysed infection rates in three ways. One, denoted 'intention-to-treat' (ITT), included the full cohort of 16,402 people. This analysis found that 56 of those in the vaccine group became infected, which was 20 people — or 26% — fewer than in the control group. That difference was not statistically significant.

Another analysis, called 'per protocol', excluded 3,860 people who failed to strictly adhere to the trial protocols, such as the calendar of vaccinations. This also showed a difference of 26%, again not statistically significant.

A third analysis — the only one to be presented on 24 September before publication of the full data — used a 'modified ITT' data crunch, which excluded seven participants who contracted HIV between the time they enrolled in the trial and their first vaccination. This lowered the number of people who became infected in the vaccine group from 56 to 51, and the number in the control group from 76 to 74, yielding a 31% difference between the groups. This just scraped into statistical significance, with a p-value of 0.04.

The small numbers of infected individuals in the trial — 132 across both vaccine and control groups — also meant that none of the subgroup analyses was statistically significant.

Caution and scepticism

The ITT analysis is generally considered as the main yardstick of the outcome of drug clinical trials, although an mITT analysis is also acceptable if agreed by independent experts. But for vaccine trials, the per-protocol analysis is the most valid, says Adel Mahmoud, former president of Merck Vaccines and now a molecular biologist at Princeton University in New Jersey .

“The results of this trial should be treated with caution and some scepticism.”

Tim Peto
University of Oxford , UK

"The results of this trial should be treated with caution and some scepticism," says Tim Peto, a researcher in tropical diseases and clinical medicine at the University of Oxford, UK. "Taken together with the disappointing results of previous vaccine studies, it is likely that the results could have been due to chance alone," he says. "The authors do not seem to acknowledge this possibility."

"My view is that a more balanced interpretation of the data is that the results show some evidence that the vaccine might be effective and that, unlike previous vaccine studies, this study cannot clearly rule out that the vaccine is ineffective," says Peto.

Nelson Michael, a researcher at the Walter Reed Army Institute of Research and director of the US Military HIV Research Program, which co-organized the trial, argues that including people who didn't stick to their shots reflects a real-world vaccination scenario, and that excluding those who were HIV-positive before the trial began was justified. Although the team admit that any protection from the vaccine is "modest", Michael says that even the trends that are not significant are worth exploring, as they might open up new avenues of research.

Blood work

The trial also failed to detect any difference between the viral load in the two cohorts. Mahmoud describes this as "very, very disturbing", because an effective vaccine would be expected to at least reduce the viral load in infected subjects. Michael, however, suggests that this finding might still prompt new vaccine leads, and that scientists should see if they can uncover the immunological origin of any possible vaccine protection.

Dan Barouch, a HIV vaccine researcher at Harvard University in Cambridge , says that the results are ultimately positive. "We don't understand why we saw the protection that we did, and the results are only modest, but nevertheless the Thai trial provides the first evidence of vaccine protection in humans. This suggests that it is in fact possible to develop an HIV vaccine."

"Everyone is saying let's try to have hope, and this is a hope that the results mean something," says Mahmoud, "but raising expectations with no fundamental scientific base is dangerous."

"The field is desperate for some kind of positive result," agrees one HIV vaccine researcher, speaking on condition of anonymity. "There is a strong tendency in the community to want to believe - it's hope versus rational science." 

References

Rerks-Ngarm, S. et al. N. Engl. J. Med. advance online publication doi:10.1056/NEJMoa0908492 (2009).

 

Data confirms 'modest' AIDS vaccine breakthrough

AFP October 20, 2009

Data from an AIDS vaccine trial in Thailand was presented to scientists on Tuesday for the first time, confirming the prototype as only a partial shield against HIV but still a pioneering achievement. Skip related content

Volunteers who received the vaccine had a 31.2-percent reduction in the risk of infection by the human immunodeficiency virus (HIV), Thai and US researchers told an international conference.

It marks the first piece of solid good news in the quest for a vaccine against AIDS, which has claimed more than 25 million lives since 1981 and left some 33 million people infected, a tally rising by around 7,400 new cases per day.

The researchers cautioned that the vaccine was still far from the mark -- generally considered to be at least 50-percent protection -- by which it could be distributed to the public.

But, they said, it was an important morale-booster, proving there were ways to prime the immune defences against a stealthy foe.

"From a scientific standpoint, it's definitely a breakthrough. But this is definitely not a public-health breakthrough," Nelson Michael of the US Military HIV Research Programme, who co-led the trial, told AFP.

He added, though: "There was a lot of introspection in the field, up until these results were initially announced and today in detail, about whether or not you would ever have a vaccine that worked.

"I think that those doubts have been dispelled to some degree. The question now is can we actually make one that can become a public-health tool."

Results from the three-year, 105-million-dollar trial were presented to the media in Bangkok on September 24, but had to cross a key credibility hurdle in the scientific community.

The study was published simultaneously in the peer-reviewed New England Journal of Medicine as Michael and his Thai counterpart, Superchai Rerks-Ngarm, made their presentation at the AIDS Vaccine 2009 conference in Paris .

The study recruited 16,395 HIV-negative volunteers, of which 8,197 received the vaccine while the 8,198 others received a harmless lookalike called a placebo.

The vaccine combines two vaccines, ALVAC and AIDSVAX, that were designed some 15 years ago and in separate trials were previously found to be safe but of negligible effectiveness.

The conclusion of 31.2-percent effectiveness derives from the number of people who became infected: 51 in the vaccinated group, against 74 in the placebo group.

The researchers acknowledged that the number of infections overall was low, but said the outcome was still statistically significant.

Protection also appears to be rather lower for people at higher risk of HIV infection and seemed to wane after the first year following vaccination, according to the trial data.

"This is a proof-of-concept vaccine," said Michael's colleague, Jerome Kim.

"This is a vaccine with a limited or modest effect. It was designed for use in Thailand , so we don't know whether it can be used in other parts of the world. It was designed and tested in a population that is at lower risk of HIV infection. Whether it can be used in high-risk populations is also unknown."

Seth Berkley, president of a New York-based advocacy group, the International AIDS Vaccine Initiative (IAVI), said the vaccine field was now generating "a lot of excitement".

In addition to the Thai vaccine, scientists were advancing on identifying potent antibodies that could intercept the AIDS virus as soon as it entered the body, he said.

Two big worries are prioritising this sudden flurry of knowledge and mustering funds for AIDS vaccine research, which fell 10 percent last year to 868 million dollars, he said.

Berkley said the mounting cost of keeping millions of people alive on anti-HIV drugs highlighted the need for a vaccine.

"We can't treat our way out of this epidemic," he said.

 

AIDS: Are the wilderness years over for vaccine research?

AFP October 21, 2009

Richard Ingham

For more than a quarter-century, their quest has been littered with setbacks while colleagues who work on HIV treatment have been showered with success.

Promising avenues have led to dead ends and long, costly trials of prototypes have ended in failure, saddling the vaccine field with a reputation for lucklessness.

But two pieces of good news have suddenly boosted morale.

Even though a vaccine still lies over the horizon, at least a path has now emerged for getting there, say experts interviewed at the AIDS Vaccine 2009 conference, ending in Paris on Thursday.

On September 3, researchers in the United States discovered two potent antibodies -- the frontline troops in the immune system -- that expose what may prove to be a viral Achilles' heel.

On September 24, US and Thai researchers unveiled the results of the biggest vaccine trial ever.

Tested among more than 16,000 Thais, shots of ALVAC and AIDSVAX vaccines offered 31.2-percent protection against the risk of infection by the human immunodeficiency virus (HIV).

This is far too weak to make it a vaccine for public use.

And nagging questions arise: why does the vaccine's effect seem to wane over time? Why does it seem to be less effective among people who are most at risk from HIV infection? And could it work in Africa , epicentre of a pandemic that has claimed 25 million lives and left some 33 million others infected?

Even so, the trial is scientific gold.

It proved at last that the immune system can be taught to recognise and devise a shield, even partially, against a notorious shape-shifting foe.

"We now have a proof of concept. It's the first time we've been able to show that," said Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases (NIAID).

"ALVAC/AIDSVAX is not in itself the answer. It's a start on the road to a vaccine, whereas, before, we didn't even know where the road was."

"The Thai tests have provided a vital pick-me-up," agreed Jean-Francois Delfraissy, director of France 's National Agency for AIDS Research (ANRS).

Seth Berkley, head of the International AIDS Vaccine Initiative (IAVI), said the research pipeline, which previously wheezed out tiny drips, was now becoming a small but steady flow.

"There's a lot of excitement," he said. "You've got the first data about protection. You've also got extremely potent antibodies that are showing new targets and there's a lot more of that coming, that field's exploding right now."

Berkley also noted that the two vaccines in the Thai trial were designed some 15 years ago. Smarter vaccines have since emerged, using different viral parts to prime the immune system and novel methods to deliver them.

Berkley pointed at progress -- among lab monkeys, not humans -- on so-called cell-mediated vaccines, in which immune cells are primed to clear out the AIDS virus after infection.

"What is happening now has sort of revitalised optimism," said Muhammad Bakari of the Muhimbili University College of Health and Allied Sciences in Tanzania .

"If you borrow the example from antiretrovirals, people thought it would take many, many years to get these drugs but the speed was much, much faster than what was thought initially. So I think we should be optimistic."

Bakari's team reported very encouraging results from an early trial, gathering 60 Tanzanian policeman, who were given either a Swedish candidate vaccine called DNA/MVA, or a placebo.

All those who were given the primer and booster showed a very strong immune response, "as high as any" in previous vaccine trials, he said.

At this early stage, the vaccine is tested for safety, not for efficacy, and delivery and dosage may have to be modified, but the results should warrant arguing for a wider trial, he said.

French scientist Francoise Barre-Sinoussi, who co-won the 2008 Nobel Prize for Medicine, cautioned that a vaccine breakthrough still depended on answering fundamental questions about HIV and the pathways of infection.

With vaccines, "you are only looking for a single piece of the jigsaw puzzle. A single piece never gives you the whole picture. It's all the pieces of the puzzle put together that give the answer."

 

Don't flag on support, AIDS chiefs say at vaccine conference

AFP October 19, 2009

Richard Ingham

"The financial crisis is of course affecting, and clearly affecting, the capacity of donors to fund international programs on AIDS," said Michel Kazatchkine, executive director of the Global Fund to Fight AIDS, Tuberculosis and Malaria.

Speaking to journalists at the start of a four-day scientific congress on AIDS vaccines, Kazatchkine said he was worried about donor retrenchment next year, when a three-year round of fund-raising comes to an end.

"2010 will be a key year when it comes to funding global health and funding AIDS prevention, treatment and AIDS science," he said.

"The risk is... that we lose the momentum, that we lose the trust and that we lose the hope that we have generated in an unprecedented movement in global health in the last eight years."

Peter Piot, former chief of the UN agency UNAIDS and now head of the Institute for Global Health in London , said he was "very worried... that attention for the AIDS response in general is fading."

"It's very ironic, (in) that it comes at a time when we have real results -- four million people on anti-retroviral therapy in lower and middle income countries (and) achievement in HIV prevention."

Piot added: "Now is not the time to decrease efforts, because the bill is then going to get higher and higher. It's a matter of 'pay now or pay later.' We know that there is money... The bailout of banks has shown that there is money, there is mega-money when it is needed."

The Paris conference, gathering around 1,000 scientists, comes on the back of the first glimmer of hope in a quarter-century quest for a vaccine against the human immunodeficiency virus (HIV).

On September 24, Thai and US researchers reported that a prototype vaccine tested among 16,000 volunteers reduced the risk of HIV infection by nearly a third.

The data was due to be scrutinised in Paris on Tuesday for the first time in a scientific arena.

Meanwhile, a Swedish researcher on Monday reported that a vaccine tested on a small scale in Tanzania may provide better protection than the Thai formula.

"We hope that our vaccine could increase protection to 50 percent," Britta Wahren, a professor emeritus at Sweden 's Karolinska Institute, told AFP.

The Swedish vaccine, called Hivis, was tested on 60 healthy policemen in Tanzania in what is called a Phase II study. The data is to be presented in Paris on Wednesday.

Several experts questioned at the conference on Monday reiterated their view that the apparent protection offered by the Thai vaccine was too low to be considered an effective shield against HIV.

They also declined to comment on the Swedish vaccine until they had seen the results.

"We need to see the data and discuss it and evaluate it," said Alan Bernstein, executive director of the Global HIV Vaccine Enterprise.

He added, though, "We're meeting at an important landmark moment in HIV vaccine research... today, HIV vaccine research is moving faster than at any time in the last 26 years."

 

Full results show AIDS vaccine is of modest help

By MARILYNN MARCHIONE,AP Medical Writer - October 21, 2009

Fresh results from the world's first successful test of an experimental AIDS vaccine confirm that it is only marginally effective and suggest that its protection against HIV infection may wane over time.

Yet the findings are exciting to scientists, who think that blood samples from the trial may show how to make a vaccine that does a better job.

The results also hint that the vaccine may work better in the general population than in those at higher risk of infection, such as gay men and intravenous drug users. It was the first time an AIDS vaccine was tested mostly in heterosexuals at average risk, and doctors have long known that how a person is exposed to HIV affects the odds of becoming infected.

"This study becomes a landmark. You can put it on a map and begin to figure out where you go from here," said Col. Jerome Kim, the U.S. Army doctor who co-led the trial.

Last month, researchers announced that a two-vaccine combination cut the risk of becoming infected with HIV by more than 31 percent in a trial of more than 16,000 volunteers in Thailand .

Full results, published online Tuesday by the New England Journal of Medicine and presented at a scientific conference in Paris , include two additional analyses that merely suggest the vaccine is beneficial, rather than providing definitive proof.

That's mostly because so few participants became infected _ only 125 people, 10 times less than in previous HIV vaccine trials, said Dr. Anthony Fauci, director the National Institute of Allergy and Infectious Diseases, the study's main sponsor.

Critics had leaked one of the analyses last week, saying it showed the original results may have been a fluke. A California-based AIDS advocacy group criticized study leaders for not giving a fuller picture when they held their news conference last month.

"The bottom line is that those results are real," even though they are not good enough to justify using this vaccine now, said Dr. Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, an alliance of governments, AIDS scientists, the World Health Organization and funders such as the Bill & Melinda Gates Foundation.

"We, for the first time, have evidence of protection, and the nitty gritty (arguments) to me don't matter a damn," Bernstein said.

Other scientists who, like Bernstein, had no role in the trial, agreed.

"It's a consistent story. There seems to be some effect. And I think it is an important study. It redirects the field to look at a different kind of vaccine and different kinds of immune responses" than what have been the focus in the past, said Dr. Lawrence Corey of the University of Washington . He heads the HIV Vaccine Trials Network, an international group of scientists who test vaccines.

The Thailand Ministry of Public Health conducted this trial, which used vaccines made from strains of HIV common in Thailand . They are ALVAC, made by Sanofi Pasteur, and AIDSVAX, originally developed by VaxGen Inc. and now held by the nonprofit Global Solutions for Infectious Diseases. The vaccines are not made from whole virus and cannot cause HIV infection.

The combo was tested in HIV-negative Thai men and women ages 18 to 30 at average risk of becoming infected. Half received four doses of ALVAC and two of AIDSVAX over six months; the rest received dummy shots. All were given condoms and counseling, and were followed for three years after vaccination ended.

New infections occurred in 51 of the 8,197 given vaccine and in 74 of the 8,198 who received dummy shots. That worked out to a 31 percent lower risk of infection for the vaccine group.

In a smaller analysis of just the 12,452 participants who received all six shots exactly on schedule, there were 86 infections _ 36 in the vaccine group and 50 in those given dummy shots.

Though not a statistically significant trend, the vaccine appeared nearly twice as effective among those at low or moderate risk of becoming infected, versus people who share needles, have contact with prostitutes or engage in other risky behaviors.

"Perhaps the requirements for protection against transmission in low-risk heterosexual persons are considerably different or less stringent," Dr. Raphael Dolin of Beth Israel Deaconess Medical Center in Boston wrote in an editorial published by the medical journal.

 

Gates Foundation grants support unusual research

Chew on this: Gates Foundation thinks gum, chocolate and malaria may have something in common

By Donna Gordon Blankinship, Associated Press Writer

October 21, 2009

SEATTLE (AP) -- What do chewing gum, chocolate and malaria have to do with each other? Not much, unless you're a young scientist exploring unusual ways to think about world health.

The Bill & Melinda Gates Foundation on Tuesday announced new grants of $100,000 each for 76 unconventional approaches to world problems.

One will help a UCLA doctoral candidate explore the idea of using chewing gum to detect malaria biomarkers in saliva. Another will give a researcher at Weill Cornell Medical College in New York the money he needs to test chocolate for combatting the malaria parasite.

Andrew Fung -- the UCLA student -- admits his idea for an inexpensive and noninvasive new way to detect malaria started out as an intellectual exercise designed to showcase his creativity for a potential postdoctorate employer. He was hoping for a job, not a research grant. He may get both.

Fung's idea was built on the need for a malaria test that does not require a blood draw and on research using saliva for detecting other diseases. On the plus side: Saliva is relatively easy to collect, the process is painless and the gum test doesn't require a battery or computer to run.

On the negative side: Saliva isn't as "clean" as blood and biomarkers aren't as prevalent in saliva as they are in blood. And since children would be a primary target of this new test, the researchers may also have some problems getting the gum away from the kids before they swallow it or hide it away.

The biomedical engineer chuckles at the issues involved in working with kids and is clearly delighted the Gates Foundation thought his unconventional idea was worth exploring.

"Very few organizations are willing to invest into that space," said Fung.

Tuesday's announcement is the third round of the Gates Foundation's Grand Challenges Exploration program to support innovative, unconventional global health research.

The five-year health research grants are designed to encourage scientists to pursue bold ideas that could lead to breakthroughs, focusing on ways to prevent and treat infectious diseases, such as HIV, malaria, tuberculosis, pneumonia and diarrheal diseases.

Nearly 3,000 proposals came in for the third round of grants. Dr. Tachi Yamada, president of the Gates Foundation's Global Health Program, says the foundation hopes this grant program will someday produce a breakthrough idea that could save untold numbers of lives.

This year's 76 grants will go to researchers from 16 countries trying to answer a wide variety of questions: Can a brief bout of exercise enhance the efficiency of the pneumococcal vaccine? Can you diagnose tuberculosis by analyzing breath samples? Should vaccines be administered under the tongue?

Unconventional science is what attracted Steven Maranz to the Grand Challenges Exploration program. The Weill Cornell Medical College researcher thought he would be a good match for the Gates Foundation program because many of his ideas are outside the norm.

"Because of my background, I usually see things a bit different from most researchers," said the American who grew up in Brazil and Africa with his anthropologist father and his mother who specialized in native language literacy. He earned his undergraduate degree in English literature, but since then has specialized in plant chemistry.

Maranz's plan to look at the effect of chocolate on the malaria parasite may sound a little strange but it's based on conventional science.

Maranz had been studying medicinal plants from West Africa and testing them to see how they affect the malaria parasite. Both current and past drugs effective at killing the malaria parasite were based on compounds that come from plants.

Since the malaria parasite has developed, over time, resistance to the drugs used to treat people, Maranz doesn't want to kill the parasite. He wants to find ways to interrupt its lifecycle in other ways.

Chocolate is a promising substance for malaria research because it binds with cholesterol and takes it out of circulation. Since the malaria parasite feeds on fat in the blood, if you take away the fat, you starve the parasite, Maranz said.

Maranz wants to kill some of the parasites but leave enough in the blood to help children develop a lifetime resistance to malaria. He will be looking at several different compounds but he thinks chocolate is the best candidate because it is rich in the right elements and is known to be safe.

His chocolate "medicine" will be delivered in a liquid form, similar to hot chocolate, because the cocoa in most chocolate bars has been altered with most of its helpful elements removed.

The scientist is quick to point out that although he feels confident of his idea, it's still an unproven hypothesis.

"This is an exploration grant. The ideas I've been talking to you about need experimental support. Nothing is proven at this point," said Maranz, speaking for himself and all the other scientists receiving Grand Challenges grants.

The Gates Foundation was created in 2000 by the Microsoft chairman and his wife.

Copyright © 2009 The Associated Press. All rights reserved. The information contained in the AP News report may not be published, broadcast, rewritten, or redistributed without the prior written authority of The Associated Press.

 

HIV vaccine trial results raise more questions

22 Oct 2009

Source: IRIN

JOHANNESBURG , 22 October 2009 - The recent news that for the first time an HIV vaccine had shown some protective effect generated widespread excitement, until it emerged that the results were based on the most promising of three different analyses of the trial findings.

The trial team in Bangkok , Thailand 's capital, announced on 24 September that a combination of two vaccines had reduced the rate of HIV infection by 31 percent in about 8,200 volunteers, compared to around the same number who were given a placebo.

A few weeks later, researchers who had seen full data from the trial told Science magazine that an analysis based only on participants who had received all six doses of the vaccine at the right times did not show a statistically significant protective effect.

It was hoped that the release of more details from the trial to coincide with the AIDS Vaccine 2009 conference taking place in Paris this week would settle the question of whether the vaccine results were really as significant as the initial announcement had suggested or a mere fluke. Instead, full results of the study, published online yesterday in the New England Journal of Medicine (NEJM) raised more questions than they answered.

The 31 percent efficacy in the initial announcement was based on a "modified intention-to-treat" analysis that included all the 16,402 trial participants, except for seven who were found to have contracted HIV before receiving any vaccinations.

A second analysis included those seven, while a third "per-protocol" analysis involving 12,452 participants - the one cited in Science magazine - found that the vaccine was only 26 percent effective. This was not enough to be statistically significant, meaning that the difference between the vaccine and the placebo arms of the trial was so small that it could have been a coincidence.

Different interpretations

Dr Jerome Kim of the US Military HIV Research Programme, who helped lead the trial, yesterday told reporters at the vaccine conference in Paris that the modified intention-to-treat analysis was the most accurate, but others disagreed.

A statistician quoted in a New York Times report placed more emphasis on the analysis that included the seven HIV-positive participants, while another did not believe that any of the analyses provided sufficient evidence the vaccine worked.

In an editorial accompanying the article, NEJM editor Raphael Dolin said that "although the merits of each type of analysis can be debated, all three yielded a possible, albeit modest, effect of the vaccine in preventing HIV infection."

The study authors also argued that, taken together, the three different analyses of the results were "consistent with a modest protective effect of vaccine", but could not explain why other findings from the trial indicated that the vaccine's efficacy appeared to decrease over time, or why it was less effective among participants at high risk of infection.

They were also unsure whether it was one of the two vaccines that produced a potentially protective effect, or the combination of the two. Dolin noted that the findings raised "a number of questions that have important implications for future directions in vaccine research", and recommended that the duration of the vaccine's effect be addressed by following up the trial participants, as well as by future trials.

According to a report by a South African news service, Health-e, Colonel Nelson Michael of the US Military HIV Research Programme, another lead investigator of the Thai trial, told a press conference in Paris that a further study of the vaccine may be conducted in South Africa , which has a much higher HIV prevalence than Thailand . The vaccine would have to be modified to contain the strain of HIV most common in sub-Saharan Africa .

 

Experts study thriving HIV "controllers" in vaccine search

21 Oct 2009

Source: Reuters

By Tan Ee Lyn

PARIS, Oct 21 (Reuters) - AIDS researchers want to expand their study of a rare group of HIV-infected people, whose immune systems naturally and mysteriously prevent the virus thriving in their bodies, to span the globe.

Studies of these "elite controllers", which aim to find an AIDS vaccine, have so far concentrated on north America . But now scientists are hoping to draw in people from Asia, Africa and Latin America .

Elite controllers are healthy, have no signs or symptoms of HIV-related disease and no need for treatment, sometimes as much as 10 years after their infection. Scientists are hoping to uncover the secret behind their robust immune systems and use it to design a vaccine for everyone.

"The hope is if we know the immune protective mechanism in elite controllers, we can target it for vaccine design," Yu Xu, assistant professor of medicine at Massachusetts General Hospital and Harvard Medical School, told Reuters after addressing an AIDS vaccine conference in Paris.

There are now 2,000 such controllers or "long term nonprogressers" mostly from the United States and Canada , whose blood samples and other data are being closely studied. Now scientists are hoping to bring in others from China , South Africa , Peru , Thailand , Brazil and other parts of the world.

At the conference, researchers detailed a trial in Thailand that appears to have shown a vaccine can protect some people -- although scientists still do not understand why or how.

Delegates are hoping to piece together a clearer picture of how to design a vaccine that would prevent infection.

DOING IT NATURALLY

An estimated 33 million people globally have HIV, and there is no cure. Drugs can control the virus and people like the controllers, who can do it naturally, are unusual.

"There are many in China . There are about 400 -- villagers infected in the 1990s and who are surviving until now. They have very low viral loads," Yu said.

"Last year we went to China and contacted some researchers and they may send us samples too," Yu said, adding that collaboration from Hong Kong may also be likely.

"We have collaboration with South Africa , Peru , Thailand , Brazil . We hope to get more patients involved. Either we can have samples or transfer some technology."

There are two classes of controllers, the more common being those with 2,000 copies of the virus or fewer in their bodies, and the even rarer elite controllers who have fewer than 50 copies.

"(Virus in the) elite controllers can't be detected at all (with regular equipment). On average, an HIV-infected person has 30,000 copies," Yu added.

Yu's colleague Mathias Lichterfeld told a news conference that controllers appear to have superior dendritic cells, one of the many types of immune cells, which appear to be a point of access for the AIDS virus.

Lichterfeld said some of the dendritic cells in the patients have higher activity of certain receptors -- molecular doorways in cells. "This offers potentially the opportunity to manipulate these two receptors to advance vaccine studies," he added.

Controllers also appear to have unusually powerful reponses to HIV in their CD8 T-cells, another type of immune cell.

"How do they maintain the power to respond so fast and effectively?" Yu asked. (Editing by Maggie Fox, David Stamp)

 

Canada study finds link between smoking crack, HIV

19 Oct 2009

Source: Reuters

* HIV may be spread via mouth wounds

* Researchers say shows need for more treatment options

* Risk of spread by drug injection was already known

By Allan Dowd

VANCOUVER, British Columbia, Oct 19 (Reuters) - Smoking crack cocaine daily adds to the risk of spreading HIV, a Canadian study published on Monday says, although researchers acknowledge they are not sure about the exact link.

The researchers, who studied the relationship between drug use and HIV in Vancouver's impoverished Downtown Eastside, one of Canada's most drug infested neighborhoods, said the findings show the need for new efforts, such as opening "safe inhalation rooms", to help drug addicts.

The nine-year study, published in the Canadian Medical Association Journal, also found that the number of addicts smoking crack cocaine on a daily basis in the neighborhood has increased steadily.

The Vancouver neighborhood's problems of drugs, poverty and homelessness are expected to attract substantial international media attention this winter, when the Pacific Coast city hosts the Winter Olympics.

Researchers said that when they began the study in 1996 they did not see evidence that smoking crack cocaine daily increased the risk of contracting HIV, the human immunodeficiency virus that causes AIDS.

But signs of risk association developed midway through the study and evidence increased over time, along with growth in the number of study participants who admitted to smoking crack, a solid variant of cocaine that is highly addictive.

Study participants who reported smoking crack on a daily basis were four times more likely to become infected with HIV than those who smoked it less often or not at all, according to the researchers.

The virus may be spread because addicts with mouth wounds share smoking pipes with HIV-infected users, but the researchers said they did not know for sure. Engaging in unprotected sex while on drug binges might also be a cause, they said.

The neighborhood has a higher rate of HIV infection and AIDs than anywhere else in Canada . By the end of the project nearly 40 percent of the study's participants smoked crack daily.

The link between the spread of HIV and injection drug use was already well known, but researcher Evan Wood of the British Columbia Centre for Excellence in HIV/AIDS acknowledged he was somewhat surprised that smoking crack also posed a risk.

The findings are evidence Canada should consider programs to treat crack smoking as a health problem rather than as a law enforcement problem, Wood said in an interview.

"The current approach simply isn't working," he said.

Among treatment ideas suggested by the research is the establishment of facilities at which drug users could smoke under medically supervised conditions with access to information that could help them fight their addictions.

Vancouver already has North America 's only sanctioned facility for users of injection drugs -- a project that has the support of local and provincial officials but which the federal Conservative government is trying to shut down.

An appeals court is expected to rule shortly on Ottawa 's challenge of a lower court decision requiring it to allow the Insite supervised injection facility to remain open. (Reporting by Allan Dowd; editing by Peter Galloway)


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