Journal article
Atazanavir Plus Ritonavir or Efavirenz as Part of a 3-Drug Regimen for Initial Treatment of HIV-1: A Randomized Trial
Annals of internal medicine, Vol.154(7), pp.445-456
2011
DOI: 10.7326/0003-4819-154-7-201104050-00316
PMID: 21320923
Abstract
Background: Limited data compare once-daily options for initial therapy for HIV-1.
Objective: To 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.
Design: A 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)
Setting: 59 AIDS Clinical Trials Group sites in the United States and Puerto Rico.
Patients: Antiretroviral-naive patients.
Intervention: Open-label atazanavir plus ritonavir or efavirenz, each given with with placebo-controlled abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine.
Measurements: Primary 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.
Results: 463 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.
Limitations: Neither 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.
Conclusion: Atazanavir plus ritonavir and efavirenz have similar antiviral activity when used with abacavir-lamivudine or tenofovir DF-emtricitabine.
Details
- Title: Subtitle
- Atazanavir Plus Ritonavir or Efavirenz as Part of a 3-Drug Regimen for Initial Treatment of HIV-1: A Randomized Trial
- Creators
- Eric S DAAR - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesCamlin TIERNEY - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesMargaret A FISCHL - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesPaul E SAX - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesKatie MOLLAN - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesChakra BUDHATHOKI - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesCatherine GODFREY - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesNasreen C JAHED - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesLaurie MYERS - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesDavid KATZENSTEIN - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesAwny FARAJALLAH - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesJames F ROONEY - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesKeith A PAPPA - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesWilliam C WOODWARD - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesKristine PATTERSON - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesHector BOLIVAR - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesConstance A BENSON - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesAnn C COLLIER - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California, United StatesAIDS Clinical Trials Group Study A5202 Team
- Contributors
- Jeffery L Meier (Contributor) - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Annals of internal medicine, Vol.154(7), pp.445-456
- Publisher
- American College of Physicians
- DOI
- 10.7326/0003-4819-154-7-201104050-00316
- PMID
- 21320923
- ISSN
- 0003-4819
- eISSN
- 1539-3704
- Language
- English
- Date published
- 2011
- Academic Unit
- Epidemiology; Internal Medicine
- Record Identifier
- 9984094550502771
Metrics
21 Record Views