Success with AIDS trials in Thailand

[WannaGo]

This is an interesting story from the BBC about how Thailand has managed to pull back from the brink of an AIDS epidemic and has been testing a vaccine combo with some success. It's a little creepy that the US military is helping to run the drug trials, though. After all, these are the same people who gave experimental nerve agent antidotes to troops during the first Gulf War and dangerous anti-malarials to soldiers in Afghanistan.

Thailand's long battle with HIV/Aids

It is no surprise that Thailand has held the largest ever trial of an HIV vaccine. The South East Asian country has long been at the forefront of the battle against HIV and Aids.

"I did this for others," said 33-year-old electrician Thanad Yomha. "It's for the next generation".

Thanad was one of more than 16,000 Thais from the provinces of Chonburi and Rayong who volunteered to take part in the trial, which was run jointly by the Thai government and US military.

The researchers had sought HIV-negative men and women between the ages of 18 and 30 years old who were at an average risk of infection.

They wanted to test a combination of two vaccines, ALVAC and AIDSVAX, which on their own had previously not worked....

...The results of the trial show that the vaccine lowered the rate of HIV infection by 31.2% compared with the placebo.

Although the results are modest and need further study, the trial has been hailed as a major scientific breakthrough by the medical world because it is the first time a vaccine has been shown to be able to prevent HIV infection.

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[Beer Chang]

The results look promising and could lead to a future breakthrough.

[lvdkeyes]

It's about 30 years now; isn't it about time?

[Beer Chang]

AIDS first reached the mainstream media in 1982.

In the early 90's Magic Johnson announced he had HIV and he's still going strong. Of course he has enough money for the best medical care.

[Wino]

It's about 30 years now; isn't it about time?

You would think that 30 years would be enough time but this mutating virus is difficult to beat. You would think they would have an answer to cancer after all these years but these things take time and money.

[WannaGo]

So, now it seems that maybe the trial wasn't as effective as the researchers had let on. Gee, who ever would have thunk it?

The LA Times is reporting that:

"...a secondary analysis of the results have suggested that the vaccine was not quite as good as people had believed, reducing infections by only 24%, which was not statistically significant, according to researchers who spoke with Science magazine. The first analysis included all 16,000 people who participated in the trial and produced the promising results. The secondary analysis -- which was part of the protocol and is considered normal for all vaccine trials -- excluded patients who did not follow the experimental regimen. When that was done, the results were less convincing, according to experts who have seen the data.

Of course, no one in the public has seen all the data yet. Full details of the trial are expected to be made public Oct. 20 at a meeting in Europe, and the researchers say they are writing a paper to be submitted to the New England Journal of Medicine. Meanwhile, all those who fervently hope for an HIV vaccine can do is wait for further revelations."

[Wino]

The proof in the pudding is when they publish all the data, and other scientists can duplicate the positive results in the study. Until then, it is wishful thinking.

[Wino]

Still another report that the good news about the AIDS vaccine might not be as positive as they first thought. Here is part of the story.

By ALICE PARK Alice Park – Tue Oct 13, 11:00 am ETIt is an emotional cycle familiar to most AIDS-vaccine researchers: the high of finally making measurable headway against HIV, followed by the crushing low of discovering that the virus has once again found a way to elude them.

It happened again on Saturday when researchers learned that the first ever successful AIDS vaccine turned out not to be the triumph they had originally hoped. In September, scientists from the National Institutes of Health (NIH) and the U.S. Army announced the results of an AIDS-vaccine study in Thailand involving more than 16,000 volunteers. The data showed that the new vaccine had protected 31% of inoculated participants from becoming infected with HIV. But a closer look at a subset of the study's volunteers now reveals that the vaccine in fact protected only 26% of the people who received it. (See pictures of Africa's AIDS crisis.)

The difference is small but critical because the new success rate of 26% falls below the threshold for statistical significance. That means that the odds of being protected from infection by the AIDS vaccine may be no better than chance.

http://news.yahoo.co.../08599192992100

[WannaGo]

It doesn't surprise me that the military would be less than honest about the results of these tests, but I'm disappointed that the National Institutes of Health would get into these political games.

[Wino]

It doesn't surprise me that the military would be less than honest about the results of these tests, but I'm disappointed that the National Institutes of Health would get into these political games.

It is strange the way these test results were published. Perhaps because so many people are anxiously waiting for a successful HIV vaccine, the military decided to release the results as they did. This paragraph from the article details the usual procedure for publishing results:

"Still, the manner in which the trial results were released raised suspicions among some in the AIDS-research community. Scientific results are generally vetted in a two-step process: first, they are published in a peer-reviewed journal, which means a panel of scientists has reviewed and evaluated the validity of the study's methods and the authors' conclusions before publication; once published, other research groups repeat or analyze the data in more depth to further ensure that they are legitimate. The results of the AIDS-vaccine trial did not benefit from either leg of this process. The investigators chose instead to announce the results in a press conference in Thailand, at the request of the Thai government, which wanted to inform its citizens of the positive findings as soon as possible. A U.S. press conference, including the U.S. Army researchers and Fauci, was held several hours later, with a promise to follow up with more detailed data in a presentation at the annual AIDS Vaccine Conference in Paris on Oct. 20."

[CrazyExpat]

Have Faith in an AIDS Vaccine

By SETH BERKLEY

Published: October 18, 2009

VACCINE researchers don’t often find themselves at the center of public controversies. But a storm has erupted over the announcement last month that an experimental AIDS vaccine tested in Thailand proved modestly effective. It was billed as a major scientific advance — the long-awaited hard evidence that it is possible to inoculate people against AIDS. But now the trial has been called into question in a way that is overblown and possibly destructive.

At a biotech conference last week, I asked a major industry scientist what he thought of the Thai trial announcement, and, although no additional data had been presented, he replied simply, “I don’t believe it.” Unfortunately, such pessimism may be hard to dispel and may ultimately thwart other efforts to develop an AIDS vaccine.

Even before this controversy erupted, it had been an effort to maintain sufficient support for AIDS vaccine research and development. In 2008, private and public spending on this vital mission declined by 10 percent from the year before. A few fanatical AIDS activists have even called for ending the American government’s considerable support for AIDS vaccine research, and spending the money instead on AIDS treatment. Patient care is vital, of course, but it alone can only mitigate, not end, the pandemic.

This is why it is essential to clear things up.

The Thai study was the largest AIDS vaccine trial yet, following 16,402 volunteers for six years. It was a collaborative effort by, among others, the United States military, the National Institutes of Health and the Thai Health Ministry. (The organization I head, a nonprofit that conducts vaccine research and development but was not involved and has no commercial interest in the candidates tested.) The trial partners initially announced that the vaccine combination reduced the risk of infection by 31.2 percent in a statistically significant analysis.

A few days later, the trial collaborators began to brief researchers privately about additional data, including a second type of analysis that indicated the vaccine regimen had been slightly less effective than the first analysis suggested. This second analysis was not statistically significant, meaning that chance, rather than the protective effect of the vaccine candidate, might explain why fewer volunteers in the vaccinated group than in the placebo group were infected with H.I.V.

Some researchers questioned why both analyses weren’t announced at the same time — which certainly would have been preferable — and suggested to reporters that the second analysis called the first one into doubt. The trial sponsors say they thought the complexities of the second analysis and all additional data were best explored in a peer-reviewed paper in a scientific journal and at a presentation at the AIDS Vaccine Conference in Paris this week. But with news outlets reporting that the trial results may be a fluke, there is a risk that they will be forever tainted, whatever the final analyses show. What’s more, the stain of dubiousness may remain on all AIDS vaccine research and development.

That would be a shame. Although the candidate duo tested in the Thai trial did not prove to be a vaccine ready for the market, it may provide an unprecedented opportunity to learn how an AIDS vaccine can work. A comparison of blood samples from volunteers could indicate what specific immune responses the combination may have activated to provide protection. If so, this knowledge could help scientists improve upon the more promising candidates that have emerged since the trial candidates were designed a decade ago, and determine which ones are most likely to work.

This illustrates why the controversy over statistical significance is exaggerated. Whether you consider the first or second analysis, the observed effect of the Thai candidates was either just above or below the level of statistical significance. Statisticians will tell you it is possible to observe an effect and have reason to think it’s real even if it’s not statistically significant. And if you think it’s real, you ought to examine it carefully.

Even if the Thai vaccine regimen turns out, on examination, to have had no real benefit, researchers will still learn from the trial, as they do from every study. Moreover, other noteworthy advances featured at the Paris conference this week will offer fresh hope for an AIDS vaccine. Years of investment and dogged science are providing leads for solving one of today’s most pressing research challenges. Some 7,400 new H.I.V. infections occur daily throughout the world. Clearly we need better methods of preventing the spread of H.I.V., and no public health intervention is more powerful or cost-effective against infectious disease than a vaccine.

http://www.nytimes.com/2009/10/19/opinion/19berkley.html?_r=1

[Wino]

This last paragraph in the article says it all. "Even if the Thai vaccine regimen turns out, on examination, to have had no real benefit, researchers will still learn from the trial, as they do from every study. Moreover, other noteworthy advances featured at the Paris conference this week will offer fresh hope for an AIDS vaccine. Years of investment and dogged science are providing leads for solving one of today’s most pressing research challenges. Some 7,400 new H.I.V. infections occur daily throughout the world. Clearly we need better methods of preventing the spread of H.I.V., and no public health intervention is more powerful or cost-effective against infectious disease than a vaccine."

We have to keep trying and the progress, although slow is still progress. We need to keep trying to find an answer.

[CrazyExpat]

Full results show AIDS vaccine is of modest help

By MARILYNN MARCHIONE (AP)

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.

http://www.google.com/hostednews/ap/article/ALeqM5iBU4mmUL2UKH1gQcOkvVYoxay6dQD9BEN0D80

[Thaimo]

It may not be so successful after all:

MUCH VAUNTED AIDS VACCINE RESULTS THROWN INTO DOUBT

Pattaya, October 20, 2009, [PDN]: the results of the world‘s largest clinical trial of a HIV vaccine conducted on a test group of 16,000 Thai volunteers have been thrown into doubt. The initial results which appeared to give a 31% protection have been challenged by data from Paris, which questioned the reliability of the statistical methods used.

The trial using a test group of 16,000 Thai volunteers, aged between 18 and 30, which was co-sponsored by the Thai government and US military, had initially claimed a 31% success rate among a sub-group of 8000, which was considered statistically significant rather than being random. Although 51 volunteers had later become infected with the HIV virus, compared with 74 only given placebos, Seth Berkley of the International Aids Vaccine Initiative, maintained the results were "exciting news and a significant scientific achievement," according to the BBC. She had also reportedly said "Now we have got a vaccine candidate that appears to show a protective effect in humans, albeit partially."

This initially encouraging news, however, received a cold reception at a Paris conference where new data was presented. The Thai results were challenged saying the result that was only just statistically significant, in addition, researchers couldn’t actually explain just how the mix of 5 vaccines were working.

Gus Cairns, from the UK HIV information charity NAM, asserted, according to the BBC, that "This means there was a one in 26 chance that the results could be due to pure chance - and that this may not reflect anything at all. That's difficult. And there is also subset analysis of this study that if you only look at the people who strictly adhered to the protocol - i.e. took all their vaccine doses - then it becomes not statistically significant."

To counterbalance the negative assertions however, certain authorities like the executive director of the Global HIV vaccine enterprise, Dr Aland Bernstein was more positive, saying if the results of the trial “hold up ..... then it is an important contribution." Similar sentiments were expressed by Alan Bernstein of the Global HIV Vaccine Enterprise, according to Reuters News Agency who said "We are not going to see all the results of the Thai trial tomorrow ... we hope this is going to lead to something more important, from 31 percent to a higher figure (of protection)."

Further bad news, however, came concerning the availability of funds for continuing research, treatment and prevention of the virus due to the economic downturn. Dr. Peter Piot of the Institute for Global Health at Imperial College London and a former head of the United Nations AIDS agency UNAIDS, according to Reuters News Agency reportedly said "I'm very concerned that AIDS is slipping off the agenda in many countries of the world due to a combination of financial and economic crises."

http://www.pattayadailynews.com/shownews.php?IDNEWS=0000010728

[WannaGo]

Science and politics should never be entangled, but so often, they are.

[Wino]

There are many research projects looking for a vaccine to prevent HIV/AIDS. Here is an article about "elite controllers;" they are HIV infected people who show no signs or symptoms of the virus. Scientists want to study more of these individuals to help with their vaccine search. Here is the story.

By Tan Ee Lyn

PARIS (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 responses 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.

http://news.yahoo.co...V9C0zGDtA2DfNdF