Long-term efficacy and safety of twice-daily saquinavir soft gelatin capsules (SGC), with or without nelfinavir, and three times daily saquinavir-SGC, in triple combination therapy for HIV infection: 100-week follow-up.

OBJECTIVES: To evaluate the long-term efficacy and safety of saquinavir soft gelatin capsules (SQV-SGC) (Fortovase) in twice-daily, with or without nelfinavir (NFV), and three-times-daily regimens. This was an extension of a 48-week study, with follow-up to 100 weeks. DESIGN: Patients were randomized to one of three treatment arms: arm A, SQV-SGC 1200 mg three times daily plus two nucleoside reverse transcriptase inhibitors (NRTIs); arm B, SQV-SGC 1,600 mg twice daily plus two NRTIs; or arm C, SQV-SGC 1200 mg twice daily plus NFV 1250 mg twice daily plus one NRTI. At week 48, patients could either withdraw or continue in the study to the common study closure date. Antiretroviral activity was assessed by changes in HIV-1 RNA values and CD4 cell counts from 48 weeks until 100 weeks. RESULTS: In the modified intention-to-treat population, the proportion of patients with HIV-1 RNA values <400 copies/ml was statistically different between arms A and C (49 vs 28%, P=0.017), and arms B and C (48 vs 28%, P=0.027). Continued suppression of HIV-1 replication (HIV-1 RNA <400 copies/ml) was observed through 100 weeks in 83% (30/36), 73% (29/40) and 62% (16/26) of patients in treatment arms A, B and C, respectively, in the on-treatment (OT) population. At 100 weeks, sustained increases were achieved in mean CD4 cell counts of +361, +273 and +309 cells/mm3, respectively (OT population). No additional adverse events or increase in the proportion of patients reporting adverse events were observed from 48 weeks to 100 weeks. CONCLUSIONS: This study demonstrates the long-term efficacy and safety of SQV-SGC twice daily, with or without NFV, and three times daily, in triple combination therapy for HIV-1-infected patients. However, the evidence suggests that long-term treatment with SQV-SGC plus NFV may be less acceptable to patients.

Efficacy and safety of twice-daily versus three-times daily saquinavir soft gelatin capsules as part of triple combination therapy for HIV-1 infection.

OBJECTIVE: The objective of this study was to determine whether a triple therapy regimen incorporating twice-daily saquinavir is as effective as a three-times daily regimen. METHODS: This was an open-label, Phase III, multicentre, 48-week study involving 837 HIV-1-infected patients randomised to one of the following: saquinavir soft gel capsule (SGC) 1200 mg three-times daily, plus two nucleoside reverse transcriptase inhibitors (NRTIs) (arm A); saquinavir SGC 1,600 mg twice-daily, plus two NRTIs (arm B); saquinavir SGC 1,200 mg twice-daily and nelfinavir 1,250 mg twice-daily, plus a single NRTI (arm C). The primary outcome measure was the virological response in arm A versus B and in arm A versus C with respect to the percentage of patients whose plasma HIV-1 RNA levels fell below the level of quantification for the Amplicor assay (<400 copies/ml) at weeks 24 and 48. RESULTS: At 48 weeks, the percentage of patients with plasma HIV-1 RNA levels <400 copies/ml was 47.1% (arm A), 45.3% (arm B) and 42.7% (arm C) in the intention-to-treat analysis. The treatment difference between arm B-arm A was -1.8% (95% confidence intervals -10.1, 6.5) and for arm C-arm A was -4.5% (95% confidence intervals -12.7, 3.7) in the intention-to-treat analysis. These differences fell within the maximum allowable difference (+/- 12%) for arm B compared with arm A. At week 24, the percentage of patients with HIV-1 RNA levels <400 copies/ml was 59.6% (arm A), 57.6% (arm B) and 51.3% (arm C). CONCLUSIONS: A twice-daily triple therapy regimen incorporating saquinavir SGC plus two NRTIs was of equivalent efficacy to the three-times daily regimen studied. All regimens were generally well tolerated.