Hepatic safety of tipranavir plus ritonavir (TPV/r)-based antiretroviral combinations: effect of hepatitis virus co-infection and pre-existing fibrosis

• Published in: Journal of antimicrobial chemotherapy Vol. 63; no. 1; pp. 178 - 183
• Main Authors: Macías, Juan, Orihuela, Francisco, Rivero, Antonio, Viciana, Pompeyo, Márquez, Manuel, Portilla, Joaquín, Ríos, María J., Muñoz, Leopoldo, Pasquau, Juan, Castaño, Manuel A., Abdel-Kader, Laila, Pineda, Juan A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-01-2009; Oxford Publishing Limited (England)
• Subjects: Adult; Anti-Retroviral Agents - adverse effects; Anti-Retroviral Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Female; Gastroenterology. Liver. Pancreas. Abdomen; HBV; HCV; Hepatitis B virus; Hepatitis C virus; Hepatitis C, Chronic; hepatotoxicity; HIV; HIV Infections - complications; HIV Infections - drug therapy; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Liver; Liver Cirrhosis; liver fibrosis; Liver Function Tests; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Other diseases. Semiology; Pharmacology; Pharmacology. Drug treatments; Pyridines - adverse effects; Pyridines - therapeutic use; Pyrones - adverse effects; Pyrones - therapeutic use; Risk factors; Ritonavir - adverse effects; Ritonavir - therapeutic use; Transaminases - blood; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral hepatitis; liver fibrosis; HCV; HBV; hepatotoxicity; Antiretroviral agent; Ritonavir; Toxicity; Liver; Orthohepadnavirus; Non peptide compound; Hepatic disease; Viral hepatitis; Tipranavir; Hepadnaviridae; Antiviral; Safety; Hepatitis B virus; Hepatotoxicity; Viral hepatitis C; Hepatic fibrosis; Immunopathology; Drug combination; Enzyme; Enzyme inhibitor; AIDS; Immune deficiency; Infection; Virus; Peptidases; Viral disease; Hydrolases; Digestive diseases; Flaviviridae; Hepatitis C virus; Hepacivirus; Protease inhibitor
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkn429

Objectives The aim of this study was to evaluate the incidence and risk factors of severe liver events among HIV-infected patients treated with drug combinations including tipranavir boosted with ritonavir (TPV/r). Methods One hundred and fifty patients were selected because they started a regimen that included TPV/r (500/200 mg twice a day) and had clinical visits at least every 3 months. Patients who discontinued TPV/r before their first visit were included. Results Twelve (8%) individuals developed grade ≥3 transaminase elevation (G ≥ 3TE). Nine (6%) patients discontinued TPV/r due to liver events. Six (8.6%) of 70 hepatitis C virus (HCV) co-infected patients and 6 (7.5%) of 80 subjects without HCV co-infection developed G ≥ 3TE (P = 1). Liver fibrosis was evaluable in 48 (63%) of 76 individuals with hepatitis B virus and/or HCV infection. Four (13%) of 30 subjects with moderate-to-severe fibrosis and none of 18 with mild fibrosis showed G ≥ 3TE (P = 0.3). None of nine patients with cirrhosis showed G ≥ 3TE. Conclusions Liver tolerability of TPV/r was generally good in a cohort of patients with a high proportion of HCV co-infection, including subjects with advanced fibrosis. The presence of HCV co-infection was not associated with an increased risk of severe transaminase elevations.