HIV Rebounds From Low-Dose Triple Therapy

Simplified drug treatments will not always keep HIV in check, doctors report in tomorrow's New England Journal of Medicine. The study shows that cutting down from three drugs to only one or two allows the virus to make a comeback in many cases. Although the results are discouraging, the researchers hope to try the approach again when more powerful drugs are available.

Many HIV-infected patients take the much-publicized triple-drug therapy, which slashes viral loads to almost nil. But these same patients often find it tough to comply with the dosage schedule and can suffer painful side effects. In other diseases treated with multiple drugs, such as tuberculosis, patients can reduce the number of pills once the pathogen appears to be under control. Diane Havlir of the University of California, San Diego, and her colleagues decided to try this "maintenance therapy" on HIV.

The team randomly assigned 316 patients who had undergone 6 months of successful triple-drug therapy to one of three treatments. One-third began taking only the protease inhibitor, another third began taking only the other two drugs, and the last group remained on triple therapy as a control. Over the next 4 months, the viral loads in 23% of the patients in the single- and the double-therapy groups increased to a level that suggested the drugs were losing the battle. Only 4% of the patients in the control group failed to keep the virus at bay.

Havlir and her colleagues believe that the more potent drugs being developed and tested might allow maintenance therapy to work. They also note that the patients who responded most quickly to the initial triple therapy appeared not to lose ground when switched to single or double therapy, suggesting that the approach might work for these patients.

"This confirms that the only way to suppress HIV is with triple therapy," says Robert Hogg, an epidemiologist at the University of British Colombia in Vancouver. He suggests that maintenance therapy sometimes fails because the virus can hide in the brain or certain blood cells, where tests don't detect it and where drugs may not have easy access.

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