2002•JAIDS Journal of Acquired Immune Deficiency SyndromesRequires access
Simplifying Protease Inhibitor Therapy with Once-Daily Dosing of Saquinavir Soft-Gelatin Capsules/Ritonavir (1600/100 mg): HIVNAT 001.3 Study
Peter Cardiello, Rolf P. van Heeswijk, Elly A. Hassink, Preeyaporn Srasuebkul, Apicha Mahanontharit, Tarika M. Samor, Wassana Worarien, Jos H. Beijnen, Richard M. W. Hoetelmans, Kiat Ruxrungtham, David A. Cooper, Joep M. A. Lange, Praphan Phanuphak
Open publisher page 1 citations
Abstract
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/ritonavir (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, steady-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 weeks (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 (C24h) of >0.05 mg/L. Median values for the area under the plasma concentration-versus-time curve from 0 to 24 hours (AUC0-24h), maximal concentration (Cmax), and C24h for SQV were 48.1 (h.mg)/L, 6.98 mg/L, and 0.17 mg/L, respectively. Body weight was inversely correlated with SQV AUC24h and C24h(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-infected patients with plasma viral loads of <50 copies/mL.