Pharmacokinetics of indinavir/ritonavir (800/100 mg) in combination with efavirenz (600 mg) in HIV-1-infected subjects

Background: Addition of efavirenz (600 mg) to indinavir/ritonavir (800/100 mg) results in significant decreases in indinavir levels in healthy volunteers. This study evaluated the steady-state phamacokinetics of indinavir/ritonavir at 800/100 mg twice daily (bid) in combination with efavirenz at 600 mg once daily (qd) in HIV-infected Thai Subjects who used this nucleoside-sparing combination in The HIV Netherlands Australia Thailand Research Collaboration 009 study. Methods: At week 4 of the study, 12-hour pharmacokinetic profiles for indinavir/ritonavir were obtained for 20 HIV-infected subjects. For efavirenz, the concentrations at 12 hours and 24 hours (C-min) after dosing were assessed. Results: All subjects (10 males and 10 females) completed the study. The geometric mean area under the concentration versus time curve, C-min, and maximum plasma concentration of indinavir were 45.7 mg/(L (.) h) (95% confidence interval [CI], 39.8-52.5), 0.32 mg/L (95% CI, 0.24-0.44), and 11.1 mg/L (95% CI, 9.4-13.0), respectively. A > 10-fold variation in indinavir C-min was observed. All subjects had an indinavir C-min that was at least comparable with the reported mean population C-min of indinavir at 800 mg thrice daily without ritonavir (0.15 mg/L). The geometric mean concentration at 12 hours and C-min of efavirenz were 3.1 mg/L (95% CI, 2.5-3.7) and 2.1 mg/L (95% CI, 1.6-2.6), respectively. Conclusions: Despite the known pharmacokinetic interaction between efavirenz and indinavir/ritonavir, the combination of indinavir/ritonavir at 800/100 mg bid and efavirenz at 600 mg qd results in adequate minimum concentrations of both indinavir and efavirenz for treatment-naive patients.