Efficacy and Safety of Ritonavir/Indinavir 100/400 Mg Twice Daily in Combination with Two Nucleoside Analogues in Antiretroviral Treatment-Naive HIV-Infected Individuals

Abstract

Objective

To evaluate the efficacy and tolerability of indinavir/ritonavir (IDV/RTV) 400/100 mg twice daily in combination with two nucleoside reverse transcriptase inhibitors in antiretroviral-naive patients.

Design and methods

Antiviral therapy-naive patients with plasma HIV-1 RNA >5000 copies/ml were enrolled in this pilot, single-arm study. CD4 cell count and viral load were evaluated at weeks (W) 4, 12, 24 and every 3 months until W48. The primary end-point was the percentage (%) of patients with viral load <400 copies/ml at W48. Intent-to-treat (ITT) (missing values or change in treatment equalled failure) and on-treatment (OT) analyses were performed.

Results

Forty patients were enrolled. Baseline median viral load was 5.36 log₁₀ copies/ml, median CD4 count was 84 cells/mm³. At W48 by ITT analysis, the % patients with viral load <400 copies/ml was 65% (95% CI: 48–79) and 50% (95% CI: 35–65) with viral load <50 copies/ml, and 96% (26/27) (95% CI: 89–100) and 74% (95% CI: 57–91], respectively, by OT analysis. The median decrease in viral load at W48 was –3.83 log₁₀ copies/ml (–0.1; –5.19) and the median increase in CD4 was +167 cells/mm³ (6–474 cell/mm³). At W4 (34/40), the median IDV C_min was 500 ng/ml (range 5–8100) with 91% of patients with an adequate IDV C_min >150 ng/ml. Ten patients discontinued the study treatment before W48: adverse events (eight), patient's will (one) and simplification of therapy (one). Three patients were lost to follow-up. Only one virological failure occurred and was associated with poor compliance and sub-optimal concentrations of IDV/RTV.

Conclusions

IDV/RTV 400/100 mg twice daily is an effective and safe first-line antiretroviral therapy. The simplicity and the low cost of IDV/RTV is of major interest particularly in countries with limited resources.