Challenges of antiretroviral treatment in transient and drug-using populations: the SUN study.

This is an open-label, single-arm, phase 3b study (part of phase 3 development) to evaluate the efficacy and safety of Fortovase-soft gelatin formulation (saquinavir-SGC), combined with zidovudine (ZDV) and lamivudine (3TC), human immune deficiency virus type 1 in (HIV-1)-positive, antiretroviral-naive individuals. Forty-two HIV-1-positive adults with plasma HIV RNA >10,000 copies per milliliter (Roche Amplicor HIV Monitor assay) and CD4 cell count >100 cells/mm(3) were treated with SQV-SGC, 1200 mg three times per day; ZDV, 300 mg; and 3TC, 150 mg each twice per day for 48 weeks. High proportions were drug users (26%), demonstrated psychiatric disorders (alcohol abuse [14%]/depression [14%]), or were inadequately housed (5%). At 48 weeks, 50% of patients achieved viral suppression <400 copies per milliliter with 43% <20 copies per milliliter using an intent-to-treat analysis (missing values counted as virological failures). Corresponding proportions for patients remaining on therapy at 48 weeks were 91% <400 copies per milliliter and 78% <20 copies per milliliter. Most adverse events were mild. Saquinavir-SGC combined with ZDV and 3TC, achieved potent and durable HIV RNA suppression and was well tolerated over 48 weeks in an antiretroviral-naive population including high proportions of individuals considered difficult to treat, such as drug users, people with psychiatric problems and homeless individuals.

Safety and pharmacokinetics of once-daily regimens of soft-gel capsule saquinavir plus minidose ritonavir in human immunodeficiency virus-negative adults.

Human immunodeficiency virus type 1 (HIV-1) protease inhibitors have dramatically improved treatment options for HIV infection, but frequent dosing may impact adherence to highly active antiretroviral treatment regimens (HAART). Previous studies demonstrated that combined therapy with ritonavir and saquinavir allows a decrease in frequency of saquinavir dosing to twice daily. In this study, we evaluated the safety and pharmacokinetics of combining once-daily doses of the soft-gel capsule (SGC) formulation of saquinavir (saquinavir-SGC) and minidose ritonavir. Forty-four healthy HIV-negative volunteers were randomized into groups receiving once-daily doses of saquinavir-SGC (1,200 to 1,800 mg) plus ritonavir (100 to 200 mg) or a control group receiving only saquinavir-SGC (1,200 mg) three times daily. Saquinavir-SGC alone and saquinavir-SGC-ritonavir combinations were generally well tolerated, and there were no safety concerns. Addition of ritonavir (100 mg) to saquinavir-SGC (1,200 to 1,800 mg/day) increased the area under the concentration-time curve (AUC) for saquinavir severalfold, and the intersubject peak concentration in plasma and AUC variability were reduced compared to those achieved with saquinavir-SGC alone (3,600 mg/day), while trough saquinavir levels (24 h post-dose) were substantially higher than the 90% inhibitory concentration calculated from HIV-1 clinical isolates. Neither increasing the saquinavir-SGC dose to higher than 1,600 mg nor increasing ritonavir from 100 to 200 mg appeared to further enhance the AUC. These results suggest that an all once-daily HAART regimen, utilizing saquinavir-SGC plus a more tolerable low dose of ritonavir, may be feasible. Studies of once-daily saquinavir-SGC (1,600 mg) in combination with ritonavir (100 mg) in HIV-infected patients are underway.