The SPICE study: 48-week activity of combinations of saquinavir soft gelatin and nelfinavir with and without nucleoside analogues

Objectives: To compare the efficacy and safety of saquinavir soft gelatin c apsules (SQV-SGC) and nelfinavir (NFV), with or without two concomitant nuc leoside reverse transcriptase inhibitors (NRTIs), in an exploratory objecti ve to identify populations most likely to benefit from quadruple therapy. Design: Phase II/III, open-label, randomized, parallel-arm, multicenter tri al. Participants: Enrollment included 157 protease inhibitor-naive adults (grea ter than or equal to 13 years) with HIV-1 RNA greater than or equal to 10,0 00 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 ti mes 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 statis tically significantly different between arms at 16 or 48 weeks, although tr ends favored the quadruple-therapy arm. In patients experiencing virologic relapse, time to relapse was statistically significantly longer in the quad ruple-therapy arm than in the other three arms (p = .007). Quadruple therap y provided benefit in NRTI-experienced patients and those with viral loads above the median value at baseline. Adverse events were mainly mild gastroi ntestinal disorders in all treatment arms. Conclusions: Quadruple therapy, including SQV-SGC and NFV, gave a more dura ble response than triple therapy with either single protease inhibitor. Qua druple therapy might particularly benefit NRTI-experienced patients and tho se with high baseline viral loads.