Open AccessEfficacy, Safety and Pharmacokinetics of Once‐Daily Saquinavir Soft‐Gelatin Capsule/Ritonavir in Antiretroviral‐Naive, HIV‐Infected Patients
Author(s) -
Julio Montaner SG,
Schutz Malte,
Schwartz Robert,
Jayaweera Dushyantha T,
Burnside Alfred F,
Walmsley Sharon,
Saag Michael S
Publication year - 2006
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.1186/1758-2652-8-2-36
Subject(s) - saquinavir , efavirenz , medicine , ritonavir , pharmacokinetics , population , pharmacology , adverse effect , gastroenterology , viral load , virology , human immunodeficiency virus (hiv) , antiretroviral therapy , environmental health
Context 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. Setting Twenty‐six centers in the United States, Canada, and Puerto Rico. Patients A total of 171 antiretroviral naive HIV‐infected individuals were enrolled in a 48‐week, phase 3, open‐label, randomized study. Main Outcome Measure 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 C min at 24 hours of 429 ng/mL (range, 681750 ng/mL). Conclusion 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.