Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: A randomized controlled trial

Roy M. Gulick*, Heather J. Ribaudo, Cecilia M. Shikuma, Christina Lalama, Bruce R. Schackman, William A. Meyer, Edward P. Acosta, Jeffrey Schouten, Kathleen E. Squires, Christopher D. Pilcher, Robert L. Murphy, Susan L. Koletar, Margrit Carlson, Richard C. Reichman, Barbara Bastow, Karin L. Klingman, Daniel R. Kuritzkes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

204 Scopus citations


Context: Three-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. Objective: To compare the safety/efficacy of 3-drug vs 4-drug regimens for initial treatment of HIV-1 infection. Design: The 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. Interventions: Zidovudine/lamivudine plus efavirenz (3-drug regimen) vs zidovudine/lamivudine/abacavir plus efavirenz (4-drug regimen). Main Outcome Measures: Time 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. Results: Seven 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. Conclusions: In 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 Registration: Identifier: NCT00013520.

Original languageEnglish (US)
Pages (from-to)769-781
Number of pages13
Issue number7
StatePublished - Aug 16 2006

ASJC Scopus subject areas

  • General Medicine


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