Liver toxicity associated with antiretroviral therapy including efavirenz or ritonavir-boosted protease inhibitors in a cohort of HIV/hepatitis C virus co-infected patients

• Published in: Journal of antimicrobial chemotherapy 2011-11, Vol.66 (11), p.2605-2614
• Main Authors: Neukam, Karin, Mira, José A., Ruiz-Morales, Josefa, Rivero, Antonio, Collado, Antonio, Torres-Cornejo, Almudena, Merino, Dolores, de los Santos-Gil, Ignacio, Macías, Juan, González-Serrano, Mercedes, Camacho, Angela, Parra-García, Ginés, Pineda, Juan A.
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Benzoxazines - administration & dosage; Benzoxazines - adverse effects; Benzoxazines - therapeutic use; Biological and medical sciences; CD4 Lymphocyte Count; Clinical trial. Drug monitoring; Cohort Studies; Coinfection; Drug therapy; Drug Therapy, Combination; Drug toxicity and drugs side effects treatment; Female; General pharmacology; Hepacivirus - drug effects; Hepatitis; Hepatitis C; Hepatitis C - complications; Hepatitis C - drug therapy; Hepatitis C virus; HIV; HIV Infections - complications; HIV Infections - drug therapy; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - adverse effects; HIV Protease Inhibitors - therapeutic use; HIV-1 - drug effects; Human immunodeficiency virus; Humans; Liver - drug effects; Liver - enzymology; Liver - pathology; Liver - virology; Liver Cirrhosis - complications; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Ritonavir - administration & dosage; Ritonavir - adverse effects; Ritonavir - therapeutic use; Toxicity; Toxicity: digestive system; Transaminases - blood
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkr357

Objectives To compare the frequency of grade 3 or 4 transaminase elevations (TEs) in HIV/hepatitis C virus (HCV) co-infected patients who started a three-antiretroviral drug regimen including efavirenz or a ritonavir-boosted protease inhibitor (PI/r) and the influence of pre-existing significant hepatic fibrosis or cirrhosis. Patients and methods All pre-treated or treatment-naive HIV/HCV co-infected patients who started an antiretroviral regimen including two nucleos(t)ide reverse transcriptase inhibitors along with efavirenz or a PI/r in seven Spanish centres from January 2007 to December 2009 were included in this prospective study. Results Of 262 patients included in this study, 76 (29%) individuals began antiretroviral therapy (ART) including efavirenz and 186 (71%) a PI/r-based combination. The median (interquartile) follow-up was 14.0 (6.2-23.7) months. A total of 20 (7.6%) patients presented grade 3-4 TEs. Four (1.5%) subjects discontinued ART due to this adverse event. Grade 3-4 TEs were observed in 5 (6.6%) subjects receiving efavirenz and 15 (8.1%) treated with PI/r (P = 0.681). Three (6.5%) patients in the efavirenz group with significant fibrosis developed grade 3-4 TEs versus 2 (8.7%) without pre-existing significant fibrosis (P = 0.743). In the PI/r group, the corresponding figures were 10 (8.8%) and 5 (9.3%), respectively (P = 0.931). Conclusions The frequency of grade 3-4 TEs associated with efavirenz-based ART combinations under clinical practice conditions is low and similar to that found in patients receiving PI/r currently used in HIV/HCV co-infected patients. The baseline fibrosis stage does not have an impact on the development of TEs caused by these antiretroviral drugs in this population.