title: Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial.
abstract: BACKGROUND
  Women account for an increasing proportion of patients with HIV-1 but remain underrepresented in antiretroviral clinical trials.
  
  
  OBJECTIVE
  To evaluate sex-based differences in efficacy and adverse events in treatment-experienced, HIV-positive women and men receiving darunavir-ritonavir therapy over 48 weeks.
  
  
  METHODS
  Multicenter, open-label, phase 3b study designed to enroll a high proportion of women, with sample size determined on the basis of a noninferiority design with a maximum allowable difference of 15% in virologic response favoring men. (ClinicalTrials.gov registration number: NCT00381303)
  
  
  METHODS
  65 sites in the United States, Puerto Rico, and Canada.
  
  
  METHODS
  287 women and 142 men.
  
  
  METHODS
  Patients received darunavir-ritonavir, 600/100 mg twice daily, plus an investigator-selected optimized background regimen.
  
  
  METHODS
  Virologic response (HIV RNA <50 copies/mL using a time-to-loss of virologic response [TLOVR] algorithm) and adverse events were assessed over 48 weeks.
  
  
  RESULTS
  67% of patients were women; 84% of patients were black or Hispanic. A higher proportion of women discontinued treatment than men (32.8% vs. 23.2%; P = 0.042); more women than men discontinued treatment for reasons other than virologic failure. Response rates in women and men at week 48 were 50.9% and 58.5%, respectively (intention-to-treat TLOVR), and 73.0% and 73.5%, respectively (TLOVR censored for patients who withdrew for reasons other than virologic failure). The absolute difference in response, based on logistic regression and adjusted for baseline log(10) viral load and CD4(+) cell count, was -9.6 percentage points (95% CI, -19.9 to 0.7 percentage points; P = 0.067) for intention-to-treat TLOVR and -3.9 percentage points (CI, -13.9 to 6.0 percentage points; P = 0.438) for TLOVR population that censored patients who withdrew for reasons other than virologic failure. Adverse events were similar between the sexes. The most common grade 2 to 4 adverse events that were considered at least possibly treatment related in women and men were nausea (5.2% and 2.8%, respectively), diarrhea (4.5% and 4.9%, respectively), and rash (2.1% and 2.8%, respectively).
  
  
  CONCLUSIONS
  Baseline characteristics differed between sexes.
  
  
  CONCLUSIONS
  Nonsignificant, sex-based differences in response were found during the 48-week study; however, these differences were probably due to higher discontinuation rates in women, suggesting that additional efforts are needed to retain women in clinical trials.
authors.affiliation: University of California, Los Angeles, CA, USA. jscurrier@mednet.ucla.edu
authors.forename: Judith
authors.initials: J
authors.lastname: Currier
authors.forename: Dawn
authors.initials: D
authors.lastname: Averitt Bridge
authors.forename: Debbie
authors.initials: D
authors.lastname: Hagins
authors.forename: Carmen D
authors.initials: CD
authors.lastname: Zorrilla
authors.forename: Judith
authors.initials: J
authors.lastname: Feinberg
authors.forename: Robert
authors.initials: R
authors.lastname: Ryan
authors.forename: Ron
authors.initials: R
authors.lastname: Falcon
authors.forename: Alan
authors.initials: A
authors.lastname: Tennenberg
authors.forename: Joseph
authors.initials: J
authors.lastname: Mrus
authors.forename: Kathleen
authors.initials: K
authors.lastname: Squires
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D012737:Sex Factors; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir