An AIDS vaccine that has had more success in monkey experiments than any other approach has never been tested in humans. The reason: Many researchers believe the vaccine, based on a weakened--or attenuated--live virus, would be too risky. Now, a group of physicians involved in AIDS care, convinced that the potential benefits outweigh the risks, is conducting an unusual campaign to recruit a few hundred volunteers for a safety study of this approach.
The Chicago–based International Association of Physicians in AIDS Care (IAPAC) made the call for a live, attenuated HIV trial in the August issue of its journal and posted a registration form for the trial on its Internet site (www.iapac.org). IAPAC says more than a dozen people already have stepped forward.
Ronald Desrosiers, of the New England Regional Primate Research Center in Southborough, Massachusetts, first showed the power of the live, attenuated approach in a monkey study published in Science nearly 5 years ago (18 December 1992, p. 1938). Monkeys given the vaccine did not become infected later, when given a lethal strain of SIV, the simian cousin of HIV. Desrosiers has spent the past several years deleting various genes from SIV and HIV to find a weakened form that is as safe as possible, yet still able to protect animals from disease-causing isolates of the virus.
A live, attenuated AIDS vaccine would have three potential pitfalls, however. The weakened virus would still be able to replicate and might cause AIDS after, say, 30 years. It's also possible the virus could mutate into a virulent form, although Desrosiers thinks this risk can be all but eliminated by deleting enough genes. Finally, the weakened HIV still would integrate with a host cell's DNA, which theoretically could trigger cancer.
Heading the drive to sign up volunteers is AIDS clinician Charles Farthing, medical director of the AIDS Healthcare Foundation in Los Angeles, California. Farthing says he hopes the trial will show that people, like the monkeys, can control replication of the weakened virus and not suffer any immunological damage. Still, AIDS experts say a short trial wouldn't answer some key safety questions. "We're really concerned with what happens when you vaccinate 20 million people and 10 years later, 5% or 10% get lymphoma," says Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases. "You're not going to know that from [IAPAC's proposed test]."