Objectives:To compare the efficacy and safety of saquinavir soft gelatin capsules (SQV-SGC) and nelfinavir (NFV), with or without two concomitant nucleoside reverse transcriptase inhibitors (NRTIs), in an exploratory objective to identify populations most likely to benefit from quadruple therapy.
Design:Phase II/III, open-label, randomized, parallel-arm, multicenter trial.
Participants:Enrollment included 157 protease inhibitor-naive adults (≥13 years) with HIV-1 RNA ≥10,000 copies/ml; 132 participants completed 48 weeks of therapy.
Interventions:SQV-SGC 1200 mg, NFV 750 mg, SQV-SGC 800 mg plus NFV 750 mg, all with two NRTIs, and SQV-SGC 800 mg plus NFV 750 mg alone, all three times daily for 48 weeks.
Main outcome measures:Proportion of participants with HIV-1 RNA <50 copies/ ml (16 and 48 weeks); time to virologic relapse (48 weeks).
Results:Proportions of patients with HIV RNA <50 copies/ml were not statistically significantly different between arms at 16 or 48 weeks, although trends favored the quadruple-therapy arm. In patients experiencing virologic relapse, time to relapse was statistically significantly longer in the quadruple-therapy arm than in the other three arms (p = .007). Quadruple therapy provided benefit in NRTI-experienced patients and those with viral loads above the median value at baseline. Adverse events were mainly mild gastrointestinal disorders in all treatment arms.
Conclusions:Quadruple therapy, including SQV-SGC and NFV, gave a more durable response than triple therapy with either single protease inhibitor. Quadruple therapy might particularly benefit NRTI-experienced patients and those with high baseline viral loads.
Address correspondence and reprint requests to Graeme Moyle, The Kobler Clinic, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9TH U.K.
Support for this study was provided by F. Hoffmann-La Roche Ltd.
Manuscript received October 21, 1999; accepted November 29, 1999.
© 2000 Lippincott Williams & Wilkins, Inc.