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Annals of Internal Medicine
Atazanavir Plus Ritonavir or Efavirenz as Part of a 3-Drug Regimen
for Initial Treatment of HIV-1
A Randomized Trial
Eric S. Daar, MD; Camlin Tierney, PhD; Margaret A. Fischl, MD; Paul E. Sax, MD; Katie Mollan, MS; Chakra Budhathoki, PhD;
Catherine Godfrey, MD; Nasreen C. Jahed, MPH; Laurie Myers, MS; David Katzenstein, MD; Awny Farajallah, MD; James F. Rooney, MD;
Keith A. Pappa, PharmD; William C. Woodward, DO; Kristine Patterson, MD; Hector Bolivar, MD; Constance A. Benson, MD; and
Ann C. Collier, MD, for the AIDS Clinical Trials Group Study A5202 Team*
Background: Limited data compare once-daily options for initial
and 324 (70%), respectively, completed follow-up. The re- spective numbers of participants in each group who receivedtenofovir DF– emtricitabine were 465 and 464; 342 (74%) and Objective: To compare time to virologic failure; first grade-3 or -4
343 (74%) completed follow-up. Primary efficacy was similar in the sign, symptom, or laboratory abnormality (safety); and change or group that received atazanavir plus ritonavir and and the group discontinuation of regimen (tolerability) for atazanavir plus ritonavir that received efavirenz and did not differ according to whether with efavirenz-containing initial therapy for HIV-1.
abacavir–lamivudine or tenofovir DF– emtricitabine was also given.
Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 Design: A randomized equivalence trial accrued from September
to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did 2005 to November 2007, with median follow-up of 138 weeks.
not meet prespecified criteria for equivalence. The time to safety Regimens were assigned by using a central computer, stratified by (P ϭ 0.048) and tolerability (P Ͻ 0.001) events was longer in screening HIV-1 RNA level less than 100 000 copies/mL or persons given atazanavir plus ritonavir than in those given efa- 100 000 copies/mL or greater; blinding was known only to the site virenz with abacavir–lamivudine but not with tenofovir DF– pharmacist. (ClinicalTrials.gov registration number: NCT00118898) Setting: 59 AIDS Clinical Trials Group sites in the United States and
Limitations: Neither HLA-B*5701 nor resistance testing was the
standard of care when A5202 enrolled patients. The third drugs, Patients: Antiretroviral-naive patients.
atazanavir plus ritonavir and efavirenz, were open-label; the nucle-oside reverse transcriptase inhibitors were prematurely unblinded in Intervention: Open-label atazanavir plus ritonavir or efavirenz,
the high viral load stratum; and 32% of patients modified or each given with with placebo-controlled abacavir–lamivudine or discontinued treatment with their third drug.
tenofovir disoproxil fumarate (DF)– emtricitabine.
Conclusion: Atazanavir plus ritonavir and efavirenz have similar
Measurements: Primary outcomes were time to virologic failure,
antiviral activity when used with abacavir–lamivudine or tenofovir safety, and tolerability events. Secondary end points included pro- portion of patients with HIV-1 RNA level less than 50 copies/mL, Primary Funding Source: National Institutes of Health.
emergence of drug resistance, changes in CD4 cell counts, calcu-lated creatinine clearance, and lipid levels.
Ann Intern Med. 2011;154:445-456.
www.annals.org
For author affiliations, see end of text.
Results: 463 eligible patients were randomly assigned to re-
* Participating centers and individuals are listed in the Appendix (available at
ceive atazanavir plus ritonavir and 465 were assigned to receive efavirenz, both with abacavir–lamivudine; 322 (70%) This article was published at www.annals.org on 15 February 2011.
Treatment guidelines for initial HIV-1 therapy recom- now report the final results of the primary study objectives
mend 2 nucleoside reverse transcriptase inhibitors comparing atazanavir plus ritonavir against efavirenz.
(NRTIs) with a non-NRTI (NNRTI), ritonavir-boostedprotease inhibitor, or integrase inhibitor (1, 2). Abacavir–lamivudine and tenofovir disoproxil fumarate (DF)–emtricitabine are efficacious, once-daily NRTIs (3–5).
The preferred NNRTI is efavirenz, and atazanavir plus ritonavir is 1 of the preferred protease inhibitors (1, 6, 7).
AIDS Clinical Trials Group (ACTG) Study A5202 Editors’ Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446 compared efficacy, safety, and tolerability of abacavir–lamivudine or tenofovir DF– emtricitabine with atazanavir Web-Only
plus ritonavir or efavirenz. After scheduled interim data re- view, the data and safety monitoring board noted inferior virologic efficacy of abacavir–lamivudine compared with teno- fovir DF– emtricitabine among patients with HIV-1 RNA levels of 100 000 copies/mL or more at screening (8). We 2011 American College of Physicians 445

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