AIDS Vaccine Testing Goes Overseas

The NIH turned Francis down. Ever persistent, he decided to rely on private funding. He persuaded Genentech to invest $2 million in a spinoff company, VaxGen Inc., and embarked on a cross-country tour that raised $150 million from other private investors.

With that money, the trial began in 1998, mostly in gay men in the United States, Canada, Puerto Rico and the Netherlands and in intravenous drug users in Thailand -- a total of 7,500.

Punnee Pitisuttithum of Mahidol University in Bangkok, who coordinated the Thai portion of the study, remembers being holed up in a San Francisco hotel room in 2003 studying reams of data. On the fourth day, the computers spat out the final analysis. The incidence rate for those who got the vaccine was 3 percent and the incidence for those who did not get the vaccine was 3 percent. There was no difference.

Punnee, 48, ran to her room and wept. "It took us nine years to find out the VaxGen vaccine did not work," she said.

Still, Francis latched on to an interesting blip in the analysis of African Americans. Fewer of the patients who got the vaccine were infected with HIV, but there were too few volunteers to draw any conclusions. For Francis it was a signal that perhaps the vaccine was indeed doing something to help prevent infection, if only in one segment of the population.

Critics brushed off that opinion, calling it a desperate attempt to salvage something from all the years of work. Weeks after the announcement that the vaccine had failed, VaxGen was hit with a shareholder lawsuit that accused the company's officials of continuing to make positive statements about their vaccine to artificially pump up the company's stock price, despite mounting evidence that it was not effective. The suit was dismissed last year and VaxGen, under new management, remade itself into a biodefense company.

"We were naively optimistic" back then, Francis said. "Our understanding of the technology to create an AIDS vaccine is still a black box and it's going to be a long haul."

In 2005, he quit his job as president of VaxGen and founded Global Solutions for Infectious Disease, a nonprofit organization that aims to develop an AIDS vaccine. Francis works in a basement office south of San Francisco that looks more like a file room than a laboratory. After VaxGen abandoned their project, he and his researchers struck out on their own. Four of the five researchers work without pay, draining their personal savings to pay for their research as they apply for grants. Francis said recently that he expects funding from a foundation in the coming month.

Hard Sell

Francis is no longer involved in testing the VaxGen vaccine. But the failure of the big 2004 trial did not stop its inclusion in the current trial, which was begun by the U.S. Army and subsequently taken over by the NIH. Half a world away in Thailand, that effort continues.

The Thai government has approached recruiting for the trial like the U.S. government did for the military during World War II -- 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. Another sign, featuring a smiling woman, told young people to go to their nearest health center to get more information.

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 -- Francis's 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 3 1/2 years.

The idea behind the NIH trial is that maybe vaccines need to provoke both antibody and T-cell responses to protect the body from AIDS. Critics say that the potentially confusing inclusion of Francis's vaccine muddies the issue and that it should be dropped from the study.

Nearly two dozen prominent AIDS researchers wrote an opinion piece in the journal Science in early 2004 calling Francis's vaccine "completely incapable of preventing or ameliorating" HIV infection and questioning "the wisdom of the U.S. government's sponsoring" the Thailand trial. "There are adverse consequences to conducting large-scale trials of inadequate [HIV] vaccines. . . . One price for repetitive failure could be crucial erosion of confidence by the public and politicians in our capability of developing an effective AIDS vaccine."

Last summer, Sen. Tom Coburn (R-Okla.), a physician, and other members of Congress began pressing U.S. 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.

Jo, a 19-year-old mechanics student with a goatee and buzz cut, signed up in the fall and brought eight friends to a clinic one morning so that they could get more information to decide whether they, too, wanted to be test subjects.

Jo said he doesn't care about the $7.50 he will be paid for each visit or any personal benefit he will get from the trial. It's important "to do something good for the community," he said.

That thought was echoed by Supachai Rerks-Ngarm, the principal investigator for the vaccine study and an official with the Thai Ministry of Public Health, who said that when it comes to researching an AIDS vaccine, there's no such thing as wasting time or money. "If we decide not to do it," he said, "we cannot explain that we have done our best to help our people."