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

Abstract

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.