title: Liver toxicity and risk of discontinuation in HIV/hepatitis C virus-coinfected patients receiving an etravirine-containing antiretroviral regimen: influence of liver fibrosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Casado
authors.affiliation: Department of Internal Medicine, INIBIC-Complexo Universitario Hospitalario, A Coruña, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Mena
authors.affiliation: Department of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Bañón
authors.affiliation: Department of Internal Medicine, INIBIC-Complexo Universitario Hospitalario, A Coruña, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Castro
authors.affiliation: Department of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Quereda
authors.affiliation: Department of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Department of Internal Medicine, INIBIC-Complexo Universitario Hospitalario, A Coruña, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pedreira
authors.affiliation: Department of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001219:Aspartate Aminotransferases / Q000378:metabolism; D060085:Coinfection / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology; D006526:Hepatitis C / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008103:Liver Cirrhosis / Q000201:enzymology / Q000453:epidemiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011446:Prospective Studies; D011724:Pyridazines / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: etravirine; hepatotoxicity; liver fibrosis; nonnucleoside reverse transcriptase inhibitor; transient elastography