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

• Published in: Journal of antimicrobial chemotherapy 2008-04, Vol.61 (4), p.925-932
• Main Authors: Pineda, J. A., Santos, J., Rivero, A., Abdel-Kader, L., Palacios, R., Camacho, A., Lozano, F., Macías, J.
• Format: Article
• Language: English
• Subjects: Adult; Age Factors; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; antiviral therapy; Atazanavir Sulfate; Bilirubin - blood; Biological and medical sciences; CD4 Lymphocyte Count; cirrhosis; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis; hepatitis B; Hepatitis B - complications; Hepatitis B virus; hepatitis C; Hepatitis C - complications; Hepatitis C virus; HIV; HIV Infections - complications; HIV Infections - drug therapy; HIV Protease Inhibitors - toxicity; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Liver; Liver Cirrhosis - complications; liver disease; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Oligopeptides - toxicity; Other diseases. Semiology; Pharmacology. Drug treatments; Pyridines - toxicity; Ritonavir - toxicity; Toxicity; Transaminases - blood; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral hepatitis
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkn045

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 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.