Influence of Liver Fibrosis Stage on Plasma Levels of Antiretroviral Drugs in HIV-Infected Patients with Chronic Hepatitis C

Background. Most antiretrovirals are metabolized in the liver, and lower dosing could be advisable in patients with severe liver insufficiency. Methods. Plasma drug levels were measured in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)—coinfected patients receiving nevirapine (NVP), efavirenz (EFV), lopinavir/ritonavir (LPV/r), or atazanavir (ATV) with or without ritonavir. Liver fibrosis was measured using elastometry. Results. A total of 268 coinfected patients with compensated liver disease were analyzed. Mean plasma levels were 6.1 μg/mL for NVP (35 patients), 2.8 μg/mL for EFV (46 patients), 5.8 μg/mL for LPV (56 patients), 0.4 μg/mL for ATV (58 patients), and 0.7 μg/mL for ATV/r (73 patients). Overall, drug levels were higher in patients with cirrhosis than in those without cirrhosis for EFV (median, 3.4 vs. 1.9 μg/mL; P< .01) and NVP (median, 6.6 vs. 5.8 μg/mL; P = .33). EFV plasma levels above the toxic threshold (>4 μg/mL) were more frequent in patients with cirrhosis than in those without (31% vs. 3%; P < .001). The same trend was seen for NVP levels >8 μg/mL (50% vs. 27%; P = .27). By contrast, plasma levels of protease inhibitors (PIs) did not differ significantly between patients with and those without cirrhosis. Conclusion. Liver clearance of nonnucleoside reverse-transcriptase inhibitors, particularly EFV, is impaired in patients with cirrhosis. No similar effect is seen for PIs. Assessment of liver fibrosis by noninvasive tools may identify HCV/HIV-coinfected patients who might benefit from therapeutic drug monitoring to avoid drug overexposure.