Efficacy of a twice-daily antiretroviral regimen containing 100 mg ritonavir/400 mg indinavir in HIV-infected patients

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Abstract
To evaluate the pharmacokinetics, efficacy and tolerability of a low-dose boosted indinavir (IDV)/ritonavir (RTV) regimen [100 mg RTV/400 mg IDV twice daily (bid)] in patients previously receiving a standard IDV regimen [800 mg three times a day (tid)]. In a prospective, open-label, cross-over trial, patients with plasma HIV RNA < 200 copies/ml receiving an IDV-containing regimen (800 mg tid) were switched to an RTV/IDV (100/400 mg bid)-containing regimen. Minimal and maximal IDV plasma concentrations (Cmin and Cmax) were determined before the switch (day 0), at week 2 and week 4 after the switch. The CD4 cell count and plasma HIV RNA were determined at day 0, week 2 and week 4, then every 8 weeks. The primary end-point was the percentage of patients with plasma HIV RNA below 200 copies/ml at week 48. Twenty patients were enrolled. At baseline, on IDV 800 mg tid, median IDV Cmin was 194 ng/ml and median IDV Cmax was 8449 ng/ml. On RTV/IDV (100/400 mg), median IDV Cmin increased to 536 ng/ml at week 2 and 475 ng/ml at week 4, while Cmax decreased to 2983 ng/ml at week 2 and 2997 ng/ml at week 4 (P < 0.001). The median area under the IDV plasma concentration-time curve measured in seven patients was 25 126 ng.h/ml, and the IDV half-life (t1/2) was 4.4 h. All patients had plasma HIV RNA remaining < 200 copies/ml at week 48. Tolerability of RTV/IDV was excellent. RTV/IDV (100/400 mg bid) yields significantly higher IDV plasma Cmin and lower IDV Cmax values relative to the standard IDV regimen, thereby improving both tolerability and efficacy.