title: Outcomes by sex following treatment initiation with atazanavir plus ritonavir or efavirenz with abacavir/lamivudine or tenofovir/emtricitabine.
abstract: BACKGROUND
  We aimed to evaluate treatment responses to atazanavir plus ritonavir (ATV/r) or efavirenz (EFV) in initial antiretroviral regimens among women and men, and determine if treatment outcomes differ by sex.
  
  
  METHODS
  We performed a randomized trial of open-label ATV/r or EFV combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) in 1857 human immunodeficiency virus type 1-infected, treatment-naive persons enrolled between September 2005 and November 2007 at 59 sites in the United States and Puerto Rico. Associations of sex with 3 primary study endpoints of time to virologic failure, safety, and tolerability events were analyzed using Cox proportional hazards models. Model-based population pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM version VII).
  
  
  RESULTS
  Of 1857 participants, 322 were women. Women assigned to ATV/r had a higher risk of virologic failure with either nucleoside reverse transcriptase inhibitor backbone than women assigned to EFV, or men assigned to ATV/r. The effects of ATV/r and EFV upon safety and tolerability risk did not differ significantly by sex. With ABC/3TC, women had a significantly higher (32%) safety risk compared to men; with TDF/FTC, the safety risk was 20% larger for women compared to men, but not statistically significant. Women had slower ATV clearance and higher predose levels of ATV compared to men. Self-reported adherence did not differ significantly by sex.
  
  
  CONCLUSIONS
  This is the first randomized clinical trial to identify a significantly earlier time to virologic failure in women randomized to ATV/r compared to women randomized to EFV. This finding has important clinical implications given that boosted protease inhibitors are often favored over EFV in women of childbearing potential.
  
  
  BACKGROUND
  NCT00118898.
authors.affiliation: Department of Medicine Division of Infectious Diseases, Rush University Medical Center, Chicago, Illinois.
authors.forename: Kimberly Y
authors.initials: KY
authors.lastname: Smith
authors.forename: Camlin
authors.initials: C
authors.lastname: Tierney
authors.forename: Katie
authors.initials: K
authors.lastname: Mollan
authors.forename: Charles S
authors.initials: CS
authors.lastname: Venuto
authors.forename: Chakra
authors.initials: C
authors.lastname: Budhathoki
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
authors.forename: Paul
authors.initials: P
authors.lastname: Sax
authors.forename: David
authors.initials: D
authors.lastname: Katzenstein
authors.forename: Catherine
authors.initials: C
authors.lastname: Godfrey
authors.forename: Margaret
authors.initials: M
authors.lastname: Fischl
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D011647:Puerto Rico; D012737:Sex Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents
keywords: abacavir; atazanavir; efavirenz; sex; tenofovir