Liver toxicity of antiretroviral combinations including atazanavir/ritonavir in patients co-infected with HIV and hepatitis viruses: impact of pre-existing liver fibrosis

J Antimicrob Chemother. 2008 Apr;61(4):925-32. doi: 10.1093/jac/dkn045. Epub 2008 Feb 14.

Abstract

Objectives: To appraise the rate of grade 3-4 transaminase elevations (TEs) and grade 4 total bilirubin elevation (TBE) in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C or hepatitis B virus (HCV or HBV, respectively) who receive atazanavir/ritonavir. Moreover, the relationship between these events and the degree of prior liver fibrosis was evaluated.

Methods: A cohort of 189 HIV-infected patients, 175 co-infected with HCV, 4 with HBV and 10 with both, receiving atazanavir/ritonavir, was analysed. Baseline liver fibrosis was assessed in 113 (60%) patients. Twenty-four patients had cirrhosis, whereas such a diagnosis was ruled out in 58 patients.

Results: Twelve (6%) and 28 (15%) patients developed grade 3-4 TEs and grade 4 TBE, respectively. Eight (10%) of 84 patients with fibrosis >/=F2 versus 1 of 29 (3%) with F0-F1 (P = 0.51) developed grade 3-4 TEs. The frequencies of grade 3-4 TEs in patients with and without cirrhosis were 8% and 5% (P = 0.63), respectively. Grade 4 TBE was more common among patients with cirrhosis (35% versus 13%, P = 0.05) in the univariate analysis. In the multivariate study, the only predictor of grade 3-4 TEs was baseline CD4 cell count <300 cells/mm(3) [adjusted OR (AOR) (95% CI) = 8.77 (1.07-71.42), P = 0.04]. The factors independently associated with grade 4 TBE were baseline total bilirubin >1 mg/dL [AOR (95% CI) = 3.2 (1.21-8.45), P = 0.01] and age >40 years [AOR (95% CI) = 2.98 (1.19-7.47), P = 0.02].

Conclusions: Prior significant liver fibrosis or cirrhosis do not increase substantially the risk of severe TE associated with atazanavir/ritonavir in patients co-infected with HIV and hepatitis viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Atazanavir Sulfate
  • Bilirubin / blood
  • CD4 Lymphocyte Count
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / toxicity*
  • Hepatitis B / complications*
  • Hepatitis C / complications*
  • Humans
  • Liver Cirrhosis / complications*
  • Male
  • Oligopeptides / toxicity*
  • Pyridines / toxicity*
  • Ritonavir / toxicity*
  • Transaminases / blood

Substances

  • HIV Protease Inhibitors
  • Oligopeptides
  • Pyridines
  • Atazanavir Sulfate
  • Transaminases
  • Ritonavir
  • Bilirubin