title: Week 48 analysis of once-daily vs. twice-daily darunavir/ritonavir in treatment-experienced HIV-1-infected patients.
abstract: OBJECTIVE
  ODIN (Once-daily Darunavir In treatment-experieNced patients) was a phase III, 48-week, open-label study comparing once-daily vs. twice-daily darunavir/ritonavir (DRV/r) in treatment-experienced patients with no DRV resistance-associated mutations (RAMs) at screening.
  
  
  METHODS
  Patients with no DRV RAMs and receiving stable HAART for at least 12 weeks were stratified by HIV-1 RNA (≤ or > 50 000 copies/ml) and randomized to once-daily DRV/r 800/100 mg or twice-daily DRV/r 600/100 mg and an optimized background regimen (≥2 nucleoside reverse transcriptase inhibitors). Primary objective was to demonstrate noninferiority of once-daily vs. twice-daily DRV/r in confirmed virologic response (HIV-1 RNA < 50 copies/ml) at week 48.
  
  
  RESULTS
  Five hundred and ninety patients received once-daily (n = 294) or twice-daily (n = 296) DRV/r. Mean baseline HIV-1 RNA was 4.16 log10 copies/ml; median CD4 cell count was 228 cells/μl; and 53.9% had previously used at least one protease inhibitor. At week 48, 72.1% of once-daily and 70.9% of twice-daily patients achieved HIV-1 RNA less than 50 copies/ml (intent-to-treat/time-to-loss of virologic response). The difference in response between once-daily and twice-daily arms was 1.2% (95% confidence interval -6.1 to 8.5%; P < 0.001), establishing noninferiority of once-daily DRV/r versus twice-daily DRV/r. Median CD4 cell count increase was 100 (once-daily) and 94 cells/μl (twice-daily). Virologic failure rate was low and similar for both arms; only one patient (once-daily arm) developed primary protease inhibitor mutations. Once-daily DRV/r had a lower incidence of grade 2-4 triglyceride increases (5.2 vs. 11.0%, P < 0.05).
  
  
  CONCLUSIONS
  Once-daily DRV/r 800/100 mg was noninferior in virologic response to twice-daily DRV/r 600/100 mg at 48 weeks in treatment-experienced patients with no DRV RAMs, and with a more favorable lipid profile. These findings support use of once-daily DRV/r in this population.
authors.affiliation: Fundación Huesped, Buenos Aires, Argentina. pcahn@huesped.org.ar
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Jan
authors.initials: J
authors.lastname: Fourie
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Sally
authors.initials: S
authors.lastname: Hodder
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Cassy
authors.initials: C
authors.lastname: Workman
authors.forename: Tom
authors.initials: T
authors.lastname: Van De Casteele
authors.forename: Piet
authors.initials: P
authors.lastname: De Doncker
authors.forename: Erkki
authors.initials: E
authors.lastname: Lathouwers
authors.forename: Frank
authors.initials: F
authors.lastname: Tomaka
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D015497:HIV-1; D006801:Humans; D008297:Male; D012367:RNA, Viral; D019438:Ritonavir / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir