A clinical study of the combination of 100 mg ritonavir plus 800 mg indinavir as salvage therapy: Influence of increased plasma drug levels in the rate of response

Abstract

Purpose: The purpose of our study was to evaluate the efficacy of indinavir (IDV) in a twice daily dosing regimen with coadministration of 100 mg ritonavir (RTV) and to explore the influence of plasma drug levels in the rate of virologie response. Method: We performed a prospective study of 59 patients who switched to a salvage regimen with two nucleoside analogs plus the combination of 100 mg RTV plus 800 mg IDV twice daily. Pharmacokinetics of IDV and RTV were assessed in 11 patients. Results: Previous antiretroviral exposure was 44 months, and 78% and 39% of patients had previously failed regimens with either IDV or RTV. Median CD4 count was 248 x 106/L and HIV load was 3.9 Iog10 copies/mL The median number of mutations in the protease gene was 9 (3-14), predominantly at residues 82 (53%), 90 (42%), and 46 (32%). After 24 weeks, 61 % of patients had a viral load decrease greater than 1 Iog10, and 38% had a viral load below 50 copies/mL. Nephrolitiasis, hematuria, or flank pain was observed in 13 patients (22%), leading to withdrawal in six cases (10%). IDV trough levels were well above the IC95 (median 1.75 mg/L, interquartile range 1.07-2.57), but RTV trough levels were below the IC95 in 88% of patients. There was a close correlation between higher peak levels of IDV, virological response, and renal toxicity. Conclusion: RTV/IDV 100/800 mg in a twice daily dosing regimen is associated with a significant virological response in patients with antiretroviral treatment failure. The correlation between plasma drug levels, toxicity, and response suggests the usefulness of individualized drug monitoring. © 2000 Thomas Land Publishers, Inc.