Testing Issues
Asiaweek, May 1999
A new Aids vaccine is tested in Thailand
“Why am I allowing myself to be used as a guinea pig? For the millions of AIDS victims all over the world,” says Kalaya ( a pseudonym). The vegetable vendor is one of 2,500 Thai drug users volunteering to test Aidsvax B/E, an experimental vaccine. Smaller studies have been conducted elsewhere. But Thailand is the first country outside the U.S. to approve large scale (or phase-three) trials—the last and most crucial hurdle before a vaccine can be licensed for sale.
Last year, the U.S. launched a similar trial of an Aidsvax aimed at only subtype B, an HIV strain common in the West. But the Thai vaccine is tailored to combat variants more prevalent in Asia. Its California-based developer VaxGen, a spin-off from Genentech, has set a three-year trial. Thailand’s active AIDS surveillance system and past participation in HIV research made it a choice testing ground. But what’s in it for the Thais? Hope, at least, of reducing the ravages of AIDS. In 1997, Thailand repoted more than 60,000 cases – far higher than any other Asian country. Dr. Chaiyos Kunanusont, director of the health ministry’s AIDS division, insists the locals have not got the poorer end of the bargain. Tailoring its vaccine to Thai needs cost VaxGen an extra $1 million—not much as such things go. Nevertheless, Bangkok hopes participation will pay off eventually through access to the latest research as well as vaccines at lower prices.
Aidsvax has been dogged by controversy, in part because HIV is such a formidable challenge. The virus is a “moving target” that mutates so rapidly the immune response vaccines induce soon becomes ineffective. Indeed, the scientific community is still split on what will really prevent infection. Aidsvax is made up of genetically engineered copies of the gp-120 glycoprotein taken from the shell of two virus strains. It is considered one of the safest vaccines because it does not include HIV genetic material. Aidsvax stimulates the production of antibodies which normally neutralize any invading bug. But some scientists argue that to be truly effective, a vaccine must also boost the number of virus-killer T-cells to help in the body’s defense.
Doubts about efficacy led the U.S. National Institute of Health to refuse funding for similar vaccine trials in 1994. Aidsvax has since been modified and put through phase-one and phase two tests. Results show that the improved vaccine has potential. But they are not conclusive proof that the antibodies that Aidsvax induces will block HIV. “The only way to find out is through phase-three trials, just as was done in the case of the polio vaccine,” says VaxGen president, Dr. Donald Francis.
The question is timing. Last year, 50 scientists wrote to Science magazine urging that U.S. phase-three trials be delayed until more was known about immunity. In Thailand, health officials believe the time for caution is past. “How long can we wait?” asks Dr. Kachit Chopanya of the Bangkok Metropolitan Administration. If trials don’t start now, a vaccine for the sub-types in Thailand will be out of reach.” Even a partly effective product could help patients, officials say.
The volunteers, who are not paid, shrug off any downside in favor of the “public good.” Perhaps compensation lies in the chance for a group with low self-esteem to feel better about themselves. Says vocational-school student Somjit: “It is good for a drug user normally looked down upon by others to do something for society.” The issues are not so simple, of course. Consider Suthee, a cab driver. Despite warnings on intravenous drug use, he doubts he can give up his 20-year heroin habit. This high-risk behavior makes uninfected people such as Suthee suitable trial candidates – and provides a moral dilemma for doctors. Physicians are ethically bound to safeguard health. Yet proving Aidsvax’s efficacy involves candidates’ exposure to the virus in daily life. Further, the vaccine’s potential protection may cause volunteers to be more reckless.
Great effort is taken to disabuse candidates of any wishful thinking. To enroll in the program, they must first watch an educational video, take part in discussions and pass two comprehension tests. Then there’s a 10-page consent form to read and sign. Before receiving each of the bi-annual doses, volunteers are warned that the vaccine may not work or that they may get a placebo (only half of the group receive the real thing). Another warning: Volunteers may show a “false HIV positive” on standard lab tests even if not infected. This may place jobs in jeopardy, although subjects can prove they are part of a study.
There are also regular reminders to avoid needle-sharing and to practice safe sex. Still, Dr. Jose Esparza, who heads the UNAIDS program’s vaccine-development team, reckons at least 200 volunteers will contract HIV. VaxGen, which is spending about $3.2 million on the trials, will provide medical care for any harm caused by the vaccine (expected side-effects: nausea and headaches), but not for people infected because of risky lifestyles either in the U.S. or in Thailand. Under Thai guidelines on HIV patients, volunteers are entitled to a level of public care, Critics say treatments don’t compare with those in the U.S. Others call for the best possible remedies. But to Thai officials, advanced therapy is often too complicated, too expensive, and may be “unfair inducement” for candidates.
Vaccine developers argue that making companies foot anti-HIV bills may put them off such research altogether. VaxGen spent 15 years and about $50 million to develop its vaccine. And it may sink in another $50 million before it’s through, says Francis. The process is expensive, tortuous and few vaccines make it out of the laboratory. Francis adds: “Even if the companies make some money in the developed world, they could go bankrupt making vaccines for developing countries.”
All the same, AIDS care in poor countries is often pitifully inadequate. Trial guidelines being finalized by a UNAIDS ethics panel should help ensure fairness. Despite “huge asymmetries” between host countries and vaccine companies, Esparza calls for flexibility—a “protectionist” attitude in developing countries hinders research on Asian subtypes. “The tragedy is that 90% of research funds are used on anti-AIDS drugs for victims in the North, but hardly any to devise a vaccine for HIV strains in the South,” he adds.
Will Thais be able to afford the product they helped test? VaxGen has pledged to make its vaccine available at “reasonable” prices. The final cost is hard to gauge, but Francis reckons it will be “more than a few dollars” – a prohibitive sum in a nation where the average monthly income is $ 161. Public coffers are limited even if the Thai government plans to provide vaccines free or very cheap to the poor.
Meanwhile, international agencies are lobbying the World Bank and rich nations to allocate more funds for research. “The pharmaceutical industry should not have sole responsibility for making vaccines,” says Esparza. He believes it will be quicker for developing countries with know-how to devise their own vaccines and host parallel trials rather than wait for the West. India, for instance, has decided to launch its own program and is seeking international funding. Most of the 16,000 people infected each day live in developing nations. “We need a push from the South,” says Esparza.