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Abstract
HIV-NAT 001.3: The safety, efficacy and pharmacokinetics (PK) of 1,600 mg saquinavir (soft-gelatin capsules; SQV-SGC) plus low dose ritonavir (RTV, 100 mg) in a once-daily (qd) dosing regimen in HIV-1-infected Thai patients.
CARDIELLO P, VAN HEESWIJK R, MONHAPHOL T, UBOLYAM S, COOPER D, LANGE J, PHANUPHAK P
Introduction: Once-daily dosing of protease inhibitors (PIs) may enhance patient compliance, which is of paramount importance for long-term suppression of viral replication. This study explored the feasibility of switching HIV-1-infected Thai patients with an undetectable (< 50) plasma viral load (pVL) during a bid SQV-SGC-containing regimen, to a more practical qd dosing regimen of SQV-SGC 1,600 mg plus RTV 100 mg.
Methods: Patients who had a pVL < 50 copies/mL after treatment with SQV-SGC plus either Combivir (AZT/3TC) or ddI/d4T (1:1) for 112 weeks were switched to SQV-SGC 1,600 mg qd plus RTV 100 mg qd, while continuing their NRTIs. The safety and efficacy (changes in pVL and CD4 count) were evaluated after 24 weeks. A substudy explored the steady-state PK of SQV and RTV in 12 patients.
Results: The qd administration of SQV-SGC/RTV was generally well tolerated, none of the patients changed the regimen because of toxicity. After 24 weeks, 61/66 patients (92%) maintained a pVL < 50 copies/mL (the remaining 5 patients had a pVL < 300 copies/mL). The CD4 count increased from (median) 534 cells/mL at start of SQV-SGC/RTV qd to 691 cells/mL after 24 weeks (p<0.01). All 12 patients in the PK substudy (mean age 35 years, mean weight 53.5 kg, 6 males) had plasma SQV trough concentrations (C24h) above the minimal effective level of 0.05 mg/L. The median (range) values for the area under the plasma concentration-time curve from 0 to 24 h (AUC24h), the maximal concentration (Cmax) and the C24h for SQV were 48.1 (20.7-82.6) h*mg/L, 6.88 (3.17-8.45) mg/L, and 0.17 (0.05-1.32) mg/L, respectively. Bodyweight was inversely correlated with the AUC24h and the C24h of SQV (p<0.01). Plasma RTV concentrations were low (Cmax < 1.44 mg/L).
Conclusion: Both our clinical and PK results support the use of SQV-SGC/RTV 1,600/100 mg qd as a convenient regimen to maintain suppression of viral replication in patients with a pVL < 50 copies/mL, in combination with two NRTIs.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
59
Suggested Citation
"CARDIELLOP, et al.
HIV-NAT 001.3: The safety, efficacy and pharmacokinetics (PK) of 1,600 mg saquinavir (soft-gelatin capsules; SQV-SGC) plus low dose ritonavir (RTV, 100 mg) in a once-daily (qd) dosing regimen in HIV-1-infected Thai patients..
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
59"
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