Lopinavir/Ritonavir Pharmacokinetics in HIV and Hepatitis C Virus Co-Infected Patients without Liver Function Impairment

Background and objective : To assess the influence of hepatitis C virus (HCV) co-infection and the extent of liver fibrosis on lopinavir/ritonavir pharmacokinetics in HIV-infected patients without liver function impairment. Methods : Cross-sectional, comparative study enrolling HIV-infected adults receiving lopinavir/ritonavir (400mg/100mg twice daily). HIV/HCV co-infected patients were grouped as having advanced fibrosis (HCV+/FIB+, n = 7) or not (HCV+/FIB−, n = 8) based on the FIB-4 index. A full concentration-time profile was obtained for each patient, and blood samples were collected before (0), and 1, 2, 4, 6, 8, 10 and 12 hours after a lopinavir/ritonavir dose. Lopinavir and ritonavir concentrations in plasma were determined by high-performance liquid chromatography. Maximum and minimum plasma concentrations (C max and C min ), area under the plasma concentration-time curve from 0 to 12 hours (AUC 12 ), apparent oral clearance at steady state (CL ss /F), and apparent volume of distribution after oral administration (V d /F) were calculated for each individual using a non-compartmental approach. Results : Twenty-six HCV− and 22 HCV+ patients were enrolled. Lopinavir and ritonavir pharmacokinetics were comparable between HCV− and HCV+ patients. However, the V d /F of lopinavir was 125% higher in HCV+/FIB+ patients than in HCV− patients (p = 0.015) and 107% higher than in HCV+/FIB− (p = 0.040) patients. The CL ss /F of ritonavir was 40% lower in HCV+/FIB+ patients than in HCV− patients (p = 0.005) and 44% lower than in HCV+/FIB− patients (p = 0.040). Thus, for ritonavir AUC 12 , C max and C min in HCV+/FIB+ patients were 63%, 86% and 100% higher, respectively, when compared with those parameters in HCV− patients (p = 0.005, p = 0.012 and p = 0.015, respectively), and 80%, 86% and 100% higher, respectively, when compared with levels in HCV+/FIB−patients (p = 0.040, p = 0.040 and p = 0.029, respectively). Conclusion : Lopinavir exposure is similar in HIV-infected patients with or without HCV co-infection and without liver function impairment. However, ritonavir exposure may be higher in this setting, particularly in individuals with advanced liver fibrosis.