• Eric S Daar, Camlin Tierney, Margaret A Fischl, Paul E Sax, Katie Mollan, Chakra Budhathoki, Catherine Godfrey, Nasreen C Jahed, Laurie Myers, David Katzenstein, Awny Farajallah, James F Rooney, Keith A Pappa, William C Woodward, Kristine Patterson, Hector Bolivar, Constance A Benson, Ann C Collier, and AIDS Clinical Trials Group Study A5202 Team.
• Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, N-24, Torrance, CA 90502, USA. EDaar@LABioMed.org
• Ann. Intern. Med. 2011 Apr 5; 154 (7): 445456445-56.

BackgroundLimited data compare once-daily options for initial therapy for HIV-1.ObjectiveTo compare time to virologic failure; first grade-3 or -4 sign, symptom, or laboratory abnormality (safety); and change or discontinuation of regimen (tolerability) for atazanavir plus ritonavir with efavirenz-containing initial therapy for HIV-1.DesignA randomized equivalence trial accrued from September 2005 to November 2007, with median follow-up of 138 weeks. Regimens were assigned by using a central computer, stratified by screening HIV-1 RNA level less than 100 000 copies/mL or 100 000 copies/mL or greater; blinding was known only to the site pharmacist. (ClinicalTrials.gov registration number: NCT00118898)Setting59 AIDS Clinical Trials Group sites in the United States and Puerto Rico.PatientsAntiretroviral-naive patients.InterventionOpen-label atazanavir plus ritonavir or efavirenz, each given with with placebo-controlled abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine.MeasurementsPrimary outcomes were time to virologic failure, safety, and tolerability events. Secondary end points included proportion of patients with HIV-1 RNA level less than 50 copies/mL, emergence of drug resistance, changes in CD4 cell counts, calculated creatinine clearance, and lipid levels.Results463 eligible patients were randomly assigned to receive atazanavir plus ritonavir and 465 were assigned to receive efavirenz, both with abacavir-lamivudine; 322 (70%) and 324 (70%), respectively, completed follow-up. The respective numbers of participants in each group who received tenofovir DF-emtricitabine were 465 and 464; 342 (74%) and 343 (74%) completed follow-up. Primary efficacy was similar in the group that received atazanavir plus ritonavir and and the group that received efavirenz and did not differ according to whether abacavir-lamivudine or tenofovir DF-emtricitabine was also given. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did not meet prespecified criteria for equivalence. The time to safety (P = 0.048) and tolerability (P < 0.001) events was longer in persons given atazanavir plus ritonavir than in those given efavirenz with abacavir-lamivudine but not with tenofovir DF-emtricitabine.LimitationsNeither HLA-B*5701 nor resistance testing was the standard of care when A5202 enrolled patients. The third drugs, atazanavir plus ritonavir and efavirenz, were open-label; the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum; and 32% of patients modified or discontinued treatment with their third drug.ConclusionAtazanavir plus ritonavir and efavirenz have similar antiviral activity when used with abacavir-lamivudine or tenofovir DF-emtricitabine.Primary Funding SourceNational Institutes of Health.© 2011 American College of Physicians

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