Simplifying protease inhibitor therapy with once-daily dosing of saquinavir soft-gelatin capsules/ritonavir (1600/100 mg): HIVNAT 001.3 study

Objective: To determine the feasibility of switching therapy for HIV-1-infected patients with plasma viral loads of <50 HIV-1 RNA copies/mL who are receiving twice-daily saquinavir soft-gelatin capsules (SQV-SGC) Plus dual nucleoside reverse transcriptase inhibitors (NRTIs) to a regimen containing once-daily SQV-SGC/rito-navir (RTV). Design: Therapy for patients, with plasma viral loads of <50 copies/mL after 2 years of treatment with twice-daily SQV-SGC (1400 mg) plus zidovudine/lamivudine or didanosine/stavudine was switched to once-daily SQV-SGC/RTV ( 1600/100 mg) with continuing NRTI treatment. Methods: Safety and efficacy (determined by plasma viral load and CD4 cell count) were evaluated (week 24). For 12 patients. stead-state plasma pharmacokinetics of SQV was determined (week 4). Results: Once-daily SQV-SGC/RTV, was well tolerated. No patient changed regimens. After 24 weeks 64 (93%) of 69 patients had plasma viral loads of <50 copies/mL (the remaining 5 patients had plasma, viral loads of <300 copies/mL). The median CD4 cell count increased from 534/mL at the start of once-daily SQV-SGCs/RTV to 695/mL after 24 checks (p <.001). Compared with the preceding 24 weeks of treatment with twice-daily SQV-SGC, the CD4 cell count improved significantly during once-daily SQV-SGC/RTV therapy (p <.001). All Patients maintained SQV trough concentrations (C-24h) of >0.05 mg/L. Median values for the area under the plasma concentration-versus-time curve from 0 to 24 hours (AUC(0-24h)), maximal concentration (C-max). and C-24h for SQV were 48.1 6.98 mg/L. and 0.17 mg/L respectively, Body weight was inversely correlated with SQV AUC(24h) and C-24h (p <.01). Conclusions: Clinical and pharmacokinetic data support once-daily SQV-SGC/RTV ( 1600/100 mg) with two NRTIs as a convenient and safe therapeutic regimen to maintain viral suppression and immune function in HIV-1-incected patients with plasma viral loads of <50 copies/mL