World's biggest Aids gamble

Thousands of Thai volunteers are helping test an experimental vaccine.

Inside a ramshackle Buddhist temple in Thailand's Chonburi village on the country's southeastern coast, curious onlookers gathered last fall as part of the United States' biggest gamble yet on stopping the Aids pandemic. The informational meeting was almost like a game show as attractive young hosts revved up the crowd, working up to the big question, boomed out over loudspeakers: Would the audience be willing to volunteer to test an experimental HIV vaccine?

The villagers hesitated. No one moved for a full 60 seconds. Then, tentatively, they approached the three stands set up at the front, marked "Join", "Not Join" and "Unsure". For the past three years, such gatherings have been held all over Thailand, exhorting young adults to take part in the largest, most expensive, most resource-intensive Aids vaccine trial ever. Funded by the US's National Institutes of Health, it ultimately will involve 16,000 people and last three-and-a-half years.

But as the trial moves forward, at a cost of more than $120 million, some researchers are raising questions about its validity. They disparage its science, question its ethics and doubt its efficacy. One of the chief dissenters is Robert C. Gallo, who helped discover the human immuno-deficiency virus. He scoffs at the notion that the trial will be successful.

NIH scientists defend the study, arguing that even if the vaccine doesn't work, the trial may reveal new things about HIV. "With 5 million new infections each year, the luxury of time is absent," four researchers wrote in the journal Science.

When scientists identified HIV as the cause of Aids 21 years ago, they predicted that a vaccine to prevent the infection would be ready long before a treatment for the symptoms could be developed. The opposite turned out to be true.

Despite years of effort, investment in the billions of dollars and dozens of small tests in people around the world, there's still no scientific proof that a vaccine is even possible. HIV is a diabolical virus that disables the very immune responses a vaccine needs to trigger in order to work.

And yet the need is so urgent that scientists have gone forward with preliminary human tests of many vaccines on the basis of data they acknowledge is weak. The one in Thailand is the largest.

The fact that no one has ever been cured of Aids increases the urgency of finding a vaccine. "In contrast to virtually every other microbe we've come across, there isn't a documented case of anyone who ... ultimately cleared HIV from the body completely. That's why more and more research is being directed at trying to stop infection from happening in the first place," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, part of the NIH.

The US government last year spent 22 per cent of its $3 billion Aids research budget on vaccines and other preventive drugs, compared with less than 8 per cent a decade ago. Meanwhile, the Bill & Melinda Gates Foundation this year designated up to $360 million for Aids vaccine research, and the United States Congress is encouraging more research with Bills that would provide liability protection and tax benefits for drug companies.

But the science is daunting and subjects hard to come by. Scientists have been forced to travel to remote corners of the world to find communities where the infection rate is high enough to show results in a reasonable amount of time.

Spectacular flop

Thailand, where Aids is a leading cause of death, has been among the most accommodating places. The NIH effort there involves two vaccines that individually have been disappointing in previous trials. One of them, developed by a once-revered scientist in the Aids world, flopped spectacularly after an expensive test funded by private investors. The other showed little promise in early trials. Researchers cling to the hope that using them simultaneously will attack different aspects of the disease and prove effective.

The Thai government has approached recruiting for the trial like the US government did for the military during the Second World War - with a call for patriotism and a plea for people to think of the greater good. "You! Your family! Your community! Join your hands together to develop an HIV vaccine," said a yellow banner hoisted on storefronts and government buildings.

The recruiters in December exceeded their goal of enrolling 16,000 volunteers. Test subjects will receive either a placebo or a combination of two vaccines - one by former government researcher Donald Francis that provokes an antibody response, and one by Sanofi Pasteur SA of Lyon, France, that targets T-cells. The study will conclude in 2009, after all participants have been followed for three-and-a-half years.

But critics want Francis' vaccine, which had flopped during trials, to be dropped. Nearly two dozen prominent Aids researchers wrote an opinion piece in the journal Science in early 2004 calling Francis' vaccine "completely incapable of preventing or ameliorating" HIV infection.

Last summer, Senator Tom Coburn, a Republican from Oklahoma, a physician and other members of the US Congress began pressing US officials to cut government funding to the trial, to no avail.

While the controversy over the trial continues in scientific and political circles in the United States, it has not been an issue in Thailand. At the Buddhist temple that evening in November, nearly all the 174 villagers eventually overcame their hesitation and said they would be open to serving as human test subjects.