Liver toxicity and risk of discontinuation in HIV /hepatitis C virus‐coinfected patients receiving an etravirine‐containing antiretroviral regimen: influence of liver fibrosis

Objectives The aim of the study was to establish the risk of liver toxicity in HIV /hepatitis C virus ( HCV )‐coinfected patients receiving etravirine, according to the degree of liver fibrosis. Methods A prospective cohort study of 211 HIV ‐infected patients initiating an etravirine‐containing regimen was carried out. HCV coinfection was defined as a positive HCV RNA test, and baseline liver fibrosis was assessed by transient elastography. Hepatotoxicity was defined as clinical symptoms, or an aspartate aminotransferase ( AST ) or alanine aminotransferase ( ALT ) value > 5‐fold higher than the upper limit of normal if baseline values were normal, or 3.5‐fold higher if values were altered at baseline. Results Overall, 145 patients (69%) were HCV coinfected, with a lower nadir (165 versus 220 cells/μL, respectively; p = 0.03) and baseline (374 versus 498 cells/μL, respectively; p = 0.04) CD4 count than monoinfected patients. Etravirine was mainly used with two nucleoside reverse transcriptase inhibitors (129; 61%) or with a boosted protease inhibitor ( PI ) (28%), with no significant differences according to HCV serostatus. Transient elastography in 117 patients (81%) showed a median (range) stiffness value of 8.25 (3.5–69) kPa, with fibrosis stage 1 in 43 patients (37%) and fibrosis stage 4 in 28 patients (24%). During an accumulated follow‐up time of 449.3 patient‐years (median 548 days), only one patient with advanced fibrosis (50.8 kPa) had grade 3–4 liver toxicity (0.7%). Transaminases changed slightly, with no significant differences compared with baseline fibrosis, and nine and six patients had grade 1 and 2 transaminase increases, respectively. Also, HCV coinfection was not associated with a higher risk of discontinuation (25% discontinued versus 21% of monoinfected patients; p = 0.39, log‐rank test) or virological failure (8% versus 12%, respectively; p = 0.4). Conclusions Our data suggest that etravirine is a safe option for HIV / HCV ‐coinfected patients, including those with significant liver fibrosis.