Liver Toxicity of Current Antiretroviral Regimens in HIV-Infected Patients with Chronic Viral Hepatitis in a Real-Life Setting: The HEPAVIR SEG-HEP Cohort

PLoS One. 2016 Feb 5;11(2):e0148104. doi: 10.1371/journal.pone.0148104. eCollection 2016.

Abstract

Objective: To assess the current frequency of ART-associated grade 3-4 transaminase elevations (TE) and grade 4 total bilirubin elevations (TBE) in HIV-infected patients with chronic hepatitis B and/or C, who start a new regimen of ART.

Patients and methods: A total of 192 pre-treated or treatment-naive HIV infected patients with HBV and/or HCV-coinfection who started ART in eight Southern Spanish centers from July/2011-December/2013, were followed for 12 months in this prospective study.

Results: Forty-one (21.4%) subjects had been naïve to ART, median (IQR) follow-up was 11.6 (5.6-12.9) months. The most frequently initiated NRTI were tenofovir/emtricitabine [49 patients (25.5%)]. Eighty-nine (46.4%) patients started a ritonavir-boosted protease inhibitor and 77 (40.1%) individuals a NNRTI. Raltegravir and maraviroc were initiated in 24 (12.5%) and 9 (4.7%) individuals. Ten [5.21%; 95% confidence interval (CI): 2.53%-9.37%] patients presented grade 3 TE, while 8 (4.17%; 95%CI: 1.82%-8.04%) subjects showed grade 4 TBE. No episodes of grade 4 TE or ART discontinuation due to hepatotoxic events were observed. The use of ritonavir-boosted atazanavir was the only independent predictor for grade 4 TBE [adjusted odds ratio: 7.327 (95%CI: 1.417-37.89); p = 0.018] in an analysis adjusted for age, sex and baseline HIV-RNA levels, while no factor could be independently associated with grade 3-4 TE.

Conclusions: Currently, the frequency of severe ART-associated TE and TBE under real-life conditions in patients with chronic viral hepatitis is similar to what has been reported previously. However, episodes of grade 4 TE are less frequent and severe TE appears to be of lesser concern.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Bilirubin / metabolism
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / metabolism
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / metabolism
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Middle Aged
  • Transaminases / metabolism

Substances

  • Anti-HIV Agents
  • Transaminases
  • Bilirubin

Grants and funding

This work was supported by the Red de Investigación en SIDA (ISCIII-RETIC RD06/006 and ISCIII-RETIC RD12/0017), the Ministerio de Sanidad y Servicios Sociales (grant number EC11-303) and the Consejería de Salud of the Junta de Andalucía (grant number AC-0095-2013). KN is the recipient of a Miguel Servet research grant from the Instituto de Salud Carlos III (grant number CP13/00187). A.R.-J. is the recipient of a post-doctoral extension grant of the Fundación Progreso y Salud of the Junta de Andalucía (grant number RH-0024-2013). JAP is the recipient of an intensification grant from the Instituto de Salud Carlos III (grant number Programa-I3SNS).