title: Liver toxicity associated with antiretroviral therapy including efavirenz or ritonavir-boosted protease inhibitors in a cohort of HIV/hepatitis C virus co-infected patients.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain.
authors: Karin
authors: K
authors: Neukam
authors: José A
authors: JA
authors: Mira
authors: Josefa
authors: J
authors: Ruiz-Morales
authors: Antonio
authors: A
authors: Rivero
authors: Antonio
authors: A
authors: Collado
authors: Almudena
authors: A
authors: Torres-Cornejo
authors: Dolores
authors: D
authors: Merino
authors: Ignacio
authors: I
authors: de Los Santos-Gil
authors: Juan
authors: J
authors: Macías
authors: Mercedes
authors: M
authors: González-Serrano
authors: Angela
authors: A
authors: Camacho
authors: Ginés
authors: G
authors: Parra-García
authors: Juan A
authors: JA
authors: Pineda
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D060085:Coinfection; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000637:Transaminases / Q000097:blood
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D000637:Transaminases; C098320:efavirenz; D019438:Ritonavir