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Antiretroviral Cocktails Can't Be Diluted.

Enthusiasm over the potency of the new anti-HIV therapies prompted some researchers to predict that AIDS treatment would soon mimic cancer chemotherapy, with an intensive multidrug phase to induce disease remission followed by a less intense maintenance phase to consolidate it. A U.S. study and one from Europe now indicate that, without further refinements, this strategy is unlikely to succeed.

Both studies used an antiretroviral "cocktail" of zidovudine, lamivudine, and indinavir to keep circulating viral RNA below the limits of detection (less than 200 to 500 copies) in HIV-infected participants for three to six months. Participants were then randomized to continue all three drugs or to stop taking one or two.

Of 105 U.S. patients who continued all three drugs for four additional months, only 4 percent relapsed with detectable circulating viral RNA. In contrast, 23 percent of 104 patients who continued zidovudine plus lamivudine and 23 percent of 100 patients who continued indinavir alone relapsed. Of 92 European patients who continued three drugs, 9 percent relapsed, in contrast to 31 percent of 93 who continued zidovudine plus lamivudine and 22 percent of 94 who continued zidovudine plus indinavir.

Comment: The disappointing message from these studies is that (at least for currently available HIV drugs) lessening the intensity of a patient's therapy, even after months of virologic suppression, courts relapse. Whether these results can be changed by using newer drugs for longer induction periods remains to be seen.

— A Zuger

Published in Journal Watch General Medicine November 3, 1998

Citation(s):

Havlir DV et al. Maintenance antiretroviral therapies in HIV-infected subjects with undetectable plasma HIV RNA after triple-drug therapy. N Engl J Med 1998 Oct 29 339 1261-1268.

• Original article (Subscription may be required)
• Medline abstract (Free)

Pialoux G et al. A randomized trial of three maintenance regimens given after three months of induction therapy with zidovudine, lamivudine, and indinavir in previously untreated HIV-1 infected patients. N Engl J Med 1998 Oct 29 339 1269-1276.

• Original article (Subscription may be required)
• Medline abstract (Free)