Efficacy, safety and pharmacokinetics of once-daily saquinavir soft-gelatin capsule/ritonavir in antiretroviral-naive, HIV-infected patients.
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.
Montaner
Julio S G
JS
St Paul's Hospital, University of British Columbia, Vancouver, BC, Canada. jmontaner@cfenet.ubc.ca
Schutz
Malte
M
Schwartz
Robert
R
Jayaweera
Dushyantha T
DT
Burnside
Alfred F
AF
Walmsley
Sharon
S
Saag
Michael S
MS
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
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