It sounds like madness, but some AIDS researchers think that HIV-infected people may benefit if they take repeated "holidays" from their drug treatments.
Cocktails of drugs that disable two key viral enzymes have transformed the lives of people with HIV, allowing some patients to rise from their sick beds. But several AIDS experts now suggest that a sequence of two-week breaks from this "triple therapy" may boost a vital component of the immune response.
The component in question is the cytotoxic T lymphocyte (CTL) response. These white blood cells kill other cells that are infected by a virus, and so are at the vanguard of the body's battle against HIV.
Treatment holidays were debated at last month's Chicago Conference on Retroviruses and Opportunistic Infections. Franco Lori of the Research Institute for Genetic and Human Therapy in Washington DC described a patient in Berlin who started treatment with three types of anti-HIV drug soon after becoming infected. The therapy was interrupted twice due to medical complications, and subsequently stopped altogether. Two years on, levels of HIV in his blood are negligible.
Lori thinks the breaks in treatment allowed a CTL response strong enough to contain the virus. He is conducting tests on monkeys and so far his results back this theory. Animals infected with SIV, a related virus, have kept it at undetectable levels in their blood for 145 days after several stop-start triple therapy treatments.
However, anecdotal reports and animal experiments aren't enough to overturn the AIDS orthodoxy. "We now need randomised controlled trials," says Lori.
Bruce Walker of Harvard Medical School in Boston is starting a small trial to see if the immune system can be trained to keep HIV under control by stopping patients' triple therapy several times for periods of about two weeks, leaving a month or so between each treatment holiday. He will study patients who were put onto drug cocktails soon after infection, before they produced detectable antibodies to HIV. If his trial is successful in tipping the balance in favour of the immune system, it may even be possible to cease drug treatment.
Meanwhile, Bernard Hirschel of the Geneva University Hospital is planning a similar experiment with 100 patients. This week, an ethics committee will judge whether the trial should go ahead.
AIDS doctors fear that any departure from continuous triple therapy will increase the likelihood of the virus becoming drug resistant. However, experts say the real problem is continuing with therapy but failing to take the proper doses. "It seems unlikely there should be resistance if you stop all three drugs at once," says Paul Johnson of the New England Primate Center in Southborough, Massachusetts.
Until the results of clinical trials are in, however, researchers urge caution. Luc Perrin, head of clinical virology at Geneva University Hospital, says: "We should be doing these experiments, but we should be clear that's what they are-experiments, not proven treatments."
Author: Michael Day
New Scientist issue 27th March 99
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