Impact of hepatitis C and liver fibrosis on antiretroviral plasma drug concentrations in HIV-HCV co-infected patients: the HEPADOSE study

Objectives: To compare plasma antiretroviral concentrations in HIV-HCV co-infected and in matched HIV mono-infected patients. Methods: This was a cross-sectional, observational study. Antiretroviral trough concentrations (C min ) in plasma were measured in HIV-HCV co-infected patients with liver disease documented by liver biopsy, matched with HIV mono-infected patients according to gender and antiretroviral treatment. C min values in serum were measured using an HPLC method. Statistical analysis was performed using the Wilcoxon test. Results: Seventy-three HIV-HCV co-infected patients and 66 HIV-infected patients were enrolled; 70% of patients were receiving a protease inhibitor (PI)- and 30% a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. Among the 73 co-infected patients, 27 had a fibrosis score (Fibrotest ® ) of F4. Abacavir was the only nucleoside reverse transcriptase inhibitor whose trough concentrations differed between the co-infected and mono-infected groups. PI median plasma C min values were not different in the two groups, except for lopinavir, with a lower C min in the co-infected group than in the HIV-infected group (median 3673 versus 5990 ng/mL, P = 0.04), and nelfinavir, with signifcantly higher concentrations in the co-infected group. Seventy-five percent of co-infected patients scoring F4, 33% of those scoring F0-F3 and 12% of HIV-infected patients were underdosed (P=0.02). Co-infected patients receiving an NNRTI had a higher plasma C min than HIV-infected patients; median C min was 3583 versus 1494 ng/mL (P = 0.025) and 5331 versus 3954 ng/mL (P=0. 10 ) for efavirenz and nevirapine, respectively. Overall, there was a greater proportion of co-infected patients with high concentrations of both NNRTIs (15/23) compared with HIV mono-infected patients (5/21) (P= 0 . 008 ), especially in co-infected patients with an advanced liver fibrosis stage. Conclusions: Median plasma C min values differed significantly between HIV and HIV-HCV co-infected patients for abacavir, lopinavir and efavirenz. NNRTIs were strongly overdosed in HIV-HCV co-infected patients.