title: Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1.
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.
  
  
  METHODS
  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)
  
  
  METHODS
  59 AIDS Clinical Trials Group sites in the United States and Puerto Rico.
  
  
  METHODS
  Antiretroviral-naive patients.
  
  
  METHODS
  Open-label atazanavir plus ritonavir or efavirenz, each given with with placebo-controlled abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Atazanavir plus ritonavir and efavirenz have similar antiviral activity when used with abacavir-lamivudine or tenofovir DF-emtricitabine.
  
  
  BACKGROUND
  National Institutes of Health.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, N-24, Torrance, CA 90502, USA. EDaar@LABioMed.org
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Camlin
authors.initials: C
authors.lastname: Tierney
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Fischl
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Katie
authors.initials: K
authors.lastname: Mollan
authors.forename: Chakra
authors.initials: C
authors.lastname: Budhathoki
authors.forename: Catherine
authors.initials: C
authors.lastname: Godfrey
authors.forename: Nasreen C
authors.initials: NC
authors.lastname: Jahed
authors.forename: Laurie
authors.initials: L
authors.lastname: Myers
authors.forename: David
authors.initials: D
authors.lastname: Katzenstein
authors.forename: Awny
authors.initials: A
authors.lastname: Farajallah
authors.forename: James F
authors.initials: JF
authors.lastname: Rooney
authors.forename: Keith A
authors.initials: KA
authors.lastname: Pappa
authors.forename: William C
authors.initials: WC
authors.lastname: Woodward
authors.forename: Kristine
authors.initials: K
authors.lastname: Patterson
authors.forename: Hector
authors.initials: H
authors.lastname: Bolivar
authors.forename: Constance A
authors.initials: CA
authors.lastname: Benson
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; C098320:efavirenz; D019438:Ritonavir