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Four Drugs Not Better Than Three for HIV

In HIV-infected patients starting antiretroviral therapy, addition of abacavir to zidovudine, lamivudine, and efavirenz does not improve treatment results.

Standard initial therapy for HIV infection is two NRTIs plus either efavirenz or a PI. Might antiretroviral activity be better with four drugs than with three?

In the AIDS Clinical Trials Group Study A5095, a multicenter, randomized, double-blind trial, researchers compared AZT/3TC/abacavir (triple-NRTI), AZT/3TC plus efavirenz (standard 3-drug therapy), and AZT/3TC/abacavir plus efavirenz (4-drug therapy) in antiretroviral-naive adults with HIV infection. The triple-NRTI arm was discontinued early because of higher rates of virologic failure in this group than in the others. The analyses reported here were based on the 765 patients initially randomized to the remaining arms (median follow-up, 144 weeks).

The 3-drug and 4-drug regimens showed similar efficacy, as assessed by proportion of patients with virologic failure (26% and 25%, respectively) and time to virologic failure. Even among subjects with baseline viral loads >100,000 copies/mL, no difference was seen between the regimens. Toxicities were similar between groups. Drug-related hypersensitivity was suspected in 7% of patients receiving the standard 3-drug regimen and 10% of patients receiving 4-drug therapy. Non-Hispanic blacks had a higher risk for virologic failure than did non-Hispanic whites (adjusted hazard ratio 1.66, P=0.003). Although self-reported adherence rates were similar among racial/ethnic groups at weeks 24 and 48, they were significantly higher for non-Hispanic whites than for non-Hispanic blacks at earlier time points.

Comment: In HIV-infected patients initiating antiretroviral therapy, addition of abacavir to standard 3-drug therapy with AZT, 3TC, and efavirenz does not improve treatment results. Standard 3-drug therapy is sufficiently potent to provide sustained suppression of viral replication in most patients. Non-Hispanic blacks appear to have an increased risk for virologic failure with the efavirenz-based regimens used in this study, perhaps due to genetically determined differences in drug metabolism and toxicity.

— Rajesh T. Gandhi, MD

Dr. Gandhi is Assistant Professor of Medicine, Harvard Medical School, and Director of HIV Clinical Services and Education, Massachusetts General Hospital, Boston.

Published in AIDS Clinical Care September 11, 2006

Citation(s):

Gulick RM et al. Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: A randomized controlled trial. JAMA 2006 Aug 16; 296:769-81.

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