title: Differences in antiretroviral safety and efficacy by sex in a multinational randomized clinical trial.
abstract: Worldwide, 50% of human immunodeficiency virus (HIV)-infected people are women. This study was to evaluate whether the safety and efficacy outcomes of three initial antiretroviral regimens (ARVs) differed by sex.
  
  
  
  Antiretroviral regimen naive participants from nine countries in four continents were assigned to ARVs with efavirenz (EFV) plus lamivudine-zidovudine, atazanavir (ATV) plus didanosine (ddI)-EC/emtricitabine (FTC) or EFV plus FTC-tenofovir-DF. The primary objective was to estimate the sex difference on efficacy outcome of treatment failure defined as one of the following: 1. Time to 1st of confirmed virologic failure, 2. WHO Stage 4 progression or 3. death with hazard ratio (HR) and 95% confidence interval (CI) from adjusted Cox regression models.
  
  
  
  In all, 739 (47%) women and 832 (53%) men with HIV were evaluated. Women had higher pretreatment CD4+(182 vs 165 cells/mm(3); P < 0.001) and lower HIV-1 RNA (4.9 log10 vs 5.2 log10 copies/ml; P < 0.001) compared to men. Association of sex with time to regimen failure differed by treatment arm (P = 0.018). For atazanavir plus didanosine-EC plus emtricitabine, women had a longer time to treatment failure compared to men [adjusted HR (aHR) = 0.59; 95% CI 0.40-0.87]. Women were less likely to prematurely discontinue treatment prematurely (aHR = 0.74; 95% CI 0.56-0.98). Women assigned to efavirenz plus lamivudine-zidovudine were more likely to have a primary safety event compared to men (aHR = 1.49; 95% CI 1.18-1.88).
  
  
  
  Antiretroviral efficacy and safety differed by sex in this study. Consideration of potential effects of sex on antiretroviral outcomes is important for the design of future clinical trials and for HIV treatment guidelines.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Firnhaber
authors.forename: Laura M
authors.initials: LM
authors.lastname: Smeaton
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Umesh
authors.initials: U
authors.lastname: Lalloo
authors.forename: Sharla
authors.initials: S
authors.lastname: Faesen
authors.forename: Wadzanai
authors.initials: W
authors.lastname: Samaneka
authors.forename: Rosa
authors.initials: R
authors.lastname: Infante
authors.forename: Aadia
authors.initials: A
authors.lastname: Rana
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.forename: James
authors.initials: J
authors.lastname: Hakim
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Campbell
mesh_terms: D000328:Adult; D000480:Alkynes; D000069446:Atazanavir Sulfate / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use; D003521:Cyclopropanes; D004338:Drug Combinations; D000068679:Emtricitabine / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012737:Sex Factors; D000068698:Tenofovir / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; D018894:Reverse Transcriptase Inhibitors; C109078:lamivudine, zidovudine drug combination; D019259:Lamivudine; D015215:Zidovudine; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; C098320:efavirenz
keywords: ARVs; Clinical studies,; HIV,; Resource-limited settings,; Women,