title: Efficacy, safety and pharmacokinetics of once-daily saquinavir soft-gelatin capsule/ritonavir in antiretroviral-naive, HIV-infected patients.
abstract: BACKGROUND
  Once-daily HIV treatment regimens are being used in clinical practice with the objective of improving patient acceptance and adherence.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of saquinavir-soft-gelatin capsule (SGC)/ritonavir combination (1600 mg/100 mg) vs efavirenz (600 mg) both once daily and combined with 2 nucleoside analogs twice daily.
  
  
  METHODS
  Twenty-six centers in the United States, Canada, and Puerto Rico.
  
  
  METHODS
  A total of 171 antiretroviral naive HIV-infected individuals were enrolled in a 48-week, phase 3, open-label, randomized study.
  
  
  METHODS
  Proportion of patients with HIV-RNA levels < 50 copies/mL. The pharmacokinetic profile of saquinavir-SGC was analyzed in a subset of randomly selected patients.
  
  
  RESULTS
  In the primary intent-to-treat population at week 48, 51% (38/75) and 71% (55/77) of patients in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, achieved HIV-RNA suppression < 50 copies/mL (P = .5392, 95% 1-sided confidence interval [CI] = -33.5%). In the on-treatment (OT) population, 73% (38/52) and 93% (54/58) of patients in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, had effective viral suppression < 50 copies/mL (P = .5015, 95% 1-sided CI = -33.4%). Mean CD4+ cell counts increased by 239 and 204 cells/microliters (mcL), in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, in the OT analysis (P = .058). Both regimens were reasonably well tolerated, although more gastrointestinal adverse events were reported with saquinavir-SGC/ritonavir. Pharmacokinetic profiles in 6 patients showed an observed median Cmin at 24 hours of 429 ng/mL (range, 68-1750 ng/mL).
  
  
  CONCLUSIONS
  Once-daily efavirenz was statistically superior to once-daily saquinavir-SGC/ritonavir. Gastrointestinal adverse effects were commonly associated with treatment failure in the saquinavir-SGC/ritonavir arm of the study.
authors.affiliation: St Paul's Hospital, University of British Columbia, Vancouver, BC, Canada. jmontaner@cfenet.ubc.ca
authors.forename: Julio S G
authors.initials: JS
authors.lastname: Montaner
authors.forename: Malte
authors.initials: M
authors.lastname: Schutz
authors.forename: Robert
authors.initials: R
authors.lastname: Schwartz
authors.forename: Dushyantha T
authors.initials: DT
authors.lastname: Jayaweera
authors.forename: Alfred F
authors.initials: AF
authors.lastname: Burnside
authors.forename: Sharon
authors.initials: S
authors.lastname: Walmsley
authors.forename: Michael S
authors.initials: MS
authors.lastname: Saag
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D048588:Benzoxazines; D002214:Capsules; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005780:Gelatin; D015658:HIV Infections; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000008:administration & dosage* / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019258:Saquinavir / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D002214:Capsules; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D010078:Oxazines; D005780:Gelatin; C098320:efavirenz; D019258:Saquinavir; D019438:Ritonavir