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

HIV Med. 2016 Jan;17(1):62-7. doi: 10.1111/hiv.12274. Epub 2015 Jun 30.

Abstract

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.

Keywords: etravirine; hepatotoxicity; liver fibrosis; nonnucleoside reverse transcriptase inhibitor; transient elastography.

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / metabolism
  • Anti-Retroviral Agents / administration & dosage*
  • Anti-Retroviral Agents / adverse effects
  • Aspartate Aminotransferases / metabolism
  • Coinfection / drug therapy*
  • Coinfection / enzymology
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / enzymology
  • Hepatitis C / drug therapy*
  • Hepatitis C / enzymology
  • Humans
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / epidemiology*
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Nitriles
  • Prospective Studies
  • Pyridazines / administration & dosage*
  • Pyridazines / adverse effects
  • Pyrimidines
  • Treatment Outcome

Substances

  • Anti-Retroviral Agents
  • Nitriles
  • Pyridazines
  • Pyrimidines
  • etravirine
  • Aspartate Aminotransferases
  • Alanine Transaminase