Weill Medical College of Cornell University, New York, NY (Drs Gulick and Schackman); Statistical and Data Analysis Center, Harvard School of Public Health, Boston, Mass (Dr Ribaudo and Ms Lalama); University of Hawaii, Honolulu (Dr Shikuma); Quest Diagnostics Inc, Baltimore, Md (Dr Meyer); University of Alabama, Birmingham (Dr Acosta); University of Washington, Seattle (Dr Schouten); University of Southern California Medical Center, Los Angeles (Dr Squires); University of North Carolina, Chapel Hill (Dr Pilcher); Northwestern University, Chicago, Ill (Dr Murphy); Ohio State University, Columbus (Dr Koletar); University of California, Los Angeles (Dr Carlson); University of Rochester, Rochester, NY (Dr Reichman); Social & Scientific Systems Inc, Silver Spring, Md (Ms Bastow); Division of AIDS, National Institute of Allergy and Infectious Disease, Bethesda, Md (Dr Klingman); and Brigham and Womens' Hospital and Harvard Medical School, Boston (Dr Kuritzkes). Dr Squires is currently affiliated with Jefferson Medical College, Philadelphia, Pa.
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ContextThree-drug antiretroviral regimens are standard of care for initial treatment of human immunodeficiency virus 1 (HIV-1) infection, but a 4-drug regimen could improve antiretroviral activity and be more effective than a 3-drug regimen.ObjectiveTo compare the safety/efficacy of 3-drug vs 4-drug regimens for initial treatment of HIV-1 infection.DesignThe AIDS Clinical Trials Group (ACTG) A5095 study, a randomized, double-blind, placebo-controlled study with enrollment and follow-up conducted from March 22, 2001, to March 1, 2005, and enrolling treatment-naive, HIV-1–infected patients with HIV-1 RNA levels of 400 copies/mL or greater from US clinical trials units of the ACTG.InterventionsZidovudine/lamivudine plus efavirenz (3-drug regimen) vs zidovudine/lamivudine/abacavir plus efavirenz (4-drug regimen).Main Outcome MeasuresTime to virologic failure (defined as time to first of 2 successive HIV-1 RNA levels ≥200 copies/mL at or after week 16), CD4 cell count changes, and grade 3 or 4 adverse events. HIV-1 RNA data were intent-to-treat, regardless of treatment changes.ResultsSeven hundred sixty-five patients with a baseline mean HIV-1 RNA level of 4.86 log10 (72 444) copies/mL and CD4 cell count of 240 cells/mm3 were randomized. After a median 3-year follow-up, 99 (26%) of 382 and 94 (25%) of 383 patients receiving the 3-drug and 4-drug regimens, respectively, reached protocol-defined virologic failure; time to virologic failure was not significantly different (hazard ratio, 0.95; 97.5% confidence interval, 0.69–1.33; P = .73). In planned subgroup analyses, increased risk for virologic failure was seen in non-Hispanic black patients (adjusted hazard ratio, 1.66; 95% confidence interval, 1.18–2.34; P = .003). At 3 years, the HIV-1 RNA level was less than 200 copies/mL in 152 (90%) of 169 and 143 (92%) of 156 patients receiving the 3-drug and 4-drug regimens, respectively (P = .59), and less than 50 copies/mL in 144 (85%) of 169 and 137 (88%) of 156 patients (P = .39). CD4 cell count increases and grade 3 or 4 adverse events were not significantly different.ConclusionsIn treatment-naive patients, there were no significant differences between the 3-drug and 4-drug antiretroviral regimens; overall, at least approximately 80% of patients had HIV-1 RNA levels less than 50 copies/mL through 3 years. These results support current guidelines recommending 2 nucleosides plus efavirenz for initial treatment of HIV-1 infection; adding abacavir as a fourth drug provided no additional benefit.Clinical Trials Registrationclinicaltrials.gov Identifier: NCT00013520