title: Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial.
abstract: BACKGROUND
  Nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy is not suitable for all treatment-naive HIV-infected persons.
  
  
  OBJECTIVE
  To evaluate 3 nonnucleoside reverse transcriptase inhibitor-sparing initial antiretroviral regimens to show equivalence for virologic efficacy and tolerability.
  
  
  METHODS
  A phase 3, open-label study randomized in a 1:1:1 ratio with follow-up for at least 96 weeks. (ClinicalTrials.gov: NCT00811954).
  
  
  METHODS
  57 sites in the United States and Puerto Rico.
  
  
  METHODS
  Treatment-naive persons aged 18 years or older with HIV-1 RNA levels greater than 1000 copies/mL without resistance to nucleoside reverse transcriptase inhibitors or protease inhibitors.
  
  
  METHODS
  Atazanavir, 300 mg/d, with ritonavir, 100 mg/d; raltegravir, 400 mg twice daily; or darunavir, 800 mg/d, with ritonavir, 100 mg/d, plus combination emtricitabine, 200 mg/d, and tenofovir disoproxil fumarate, 300 mg/d.
  
  
  METHODS
  Virologic failure, defined as a confirmed HIV-1 RNA level greater than 1000 copies/mL at or after 16 weeks and before 24 weeks or greater than 200 copies/mL at or after 24 weeks, and tolerability failure, defined as discontinuation of atazanavir, raltegravir, or darunavir for toxicity. A secondary end point was a combination of virologic efficacy and tolerability.
  
  
  RESULTS
  Among 1809 participants, all pairwise comparisons of incidence of virologic failure over 96 weeks showed equivalence within a margin of equivalence defined as -10% to 10%. Raltegravir and ritonavir-boosted darunavir were equivalent for tolerability, whereas ritonavir-boosted atazanavir resulted in a 12.7% and 9.2% higher incidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir, respectively, primarily because of hyperbilirubinemia. For combined virologic efficacy and tolerability, ritonavir-boosted darunavir was superior to ritonavir-boosted atazanavir, and raltegravir was superior to both protease inhibitors. Antiretroviral resistance at the time of virologic failure was rare but more frequent with raltegravir.
  
  
  CONCLUSIONS
  The trial was open-label, and ritonavir was not provided.
  
  
  CONCLUSIONS
  Over 2 years, all 3 regimens attained high and equivalent rates of virologic control. Tolerability of regimens containing raltegravir or ritonavir-boosted darunavir was superior to that of the ritonavir-boosted atazanavir regimen.
  
  
  BACKGROUND
  National Institute of Allergy and Infectious Diseases.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Lennox
authors.forename: Raphael J
authors.initials: RJ
authors.lastname: Landovitz
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.forename: Ighovwerha
authors.initials: I
authors.lastname: Ofotokun
authors.forename: Lumine H
authors.initials: LH
authors.lastname: Na
authors.forename: Catherine
authors.initials: C
authors.lastname: Godfrey
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Manish
authors.initials: M
authors.lastname: Sagar
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
authors.forename: Susan E
authors.initials: SE
authors.lastname: Cohn
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.forename: Francesca
authors.initials: F
authors.lastname: Aweeka
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Fichtenbaum
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Presti
authors.forename: Susan L
authors.initials: SL
authors.lastname: Koletar
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Kristine B
authors.initials: KB
authors.lastname: Patterson
authors.forename: Constance A
authors.initials: CA
authors.lastname: Benson
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Baugh
authors.forename: Randi Y
authors.initials: RY
authors.lastname: Leavitt
authors.forename: James F
authors.initials: JF
authors.lastname: Rooney
authors.forename: Daniel
authors.initials: D
authors.lastname: Seekins
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000069446:Atazanavir Sulfate; D000069454:Darunavir; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D012367:RNA, Viral / Q000302:isolation & purification; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides / Q000627:therapeutic use; D000068698:Tenofovir; D013810:Therapeutic Equivalency; D019562:Viral Load
chemical_list: D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D003841:Deoxycytidine; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D000069454:Darunavir