Efficacy and safety of etravirine‐containing regimens in a large cohort of HIV/HCV coinfected patients according to liver fibrosis

Etravirine has become an alternative in HIV/HCV coinfected patients because of safety and lack of interactions with anti‐HCV drugs. The aim of this study was to establish the risk of liver toxicity in HIV/HCV coinfected patients receiving etravirine in the clinical setting, according to the degree of liver fibrosis and different accompanying drugs. Material and Methods Cohort study of 211 patients initiating etravirine as part of their antiretroviral regimen. HCV coinfection was defined as a positive RNA‐HCV, whereas baseline liver fibrosis was assessed by transient elastography at baseline. Hepatotoxicity was defined as an increased AST/ALT, 5‐fold higher over upper, normal limits for patients with normal baseline values, or 3.5‐fold if altered at baseline. Results HCV coinfection was observed in 145 patients (69%) with a longer time of HIV infection and time on HAART than mono‐infected patients, and a lower nadir (182 vs 227 cells/mL; p=0.02) and baseline CD4+ count (446 vs 552 cells/mL; p=0.02). Etravirine was used with two nucleoside analogues in 62%, with boosted darunavir in 17%, with raltegravir in 10%, and with darunavir plus raltegravir or maraviroc in 10% of patients without differences according to HCV serostatus. Transient elastography in 117 patients performed at etravirine initiation (median, 33 days) showed fibrosis 1 and fibrosis 4 in 37% and 24% of cases, and median stiffness value was 8.25 kPa (3.5–69). During an accumulated follow‐up of 449.3 patient‐years (median, 611 days), only one coinfected patient with fibrosis 4 (stiffness value, 50.1 kPa), receiving a rescue regimen including darunavir/r plus maraviroc plus two nucleoside analogues, developed a grade 3‐4 of liver toxicity (0.5%). There were no other episodes of liver toxicity, as defined, and only 6 (3%) and 9 patients (4%) had a grade 1 and 2 of toxicity, respectively, in most cases related to HCV coinfection (6 and 6 cases). Moreover, HCV coinfection or advanced fibrosis was not associated to a higher risk of etravirine discontinuation (26% vs 21%; p=0.27, log‐rank test) or virologic failure (9% vs 11%, p=0.56). CD4+ cell count increase was lower in HCV patients (+23 vs +86 at 6 month; p=0.02). Conclusions Etravirine is safe in HIV/HCV coinfected patients, even in presence of moderate and advanced liver fibrosis and as part of different antiretroviral regimens.