title: Liver toxicity of initial antiretroviral drug regimens including two nucleoside analogs plus one non-nucleoside analog or one ritonavir-boosted protease inhibitor in HIV/HCV-coinfected patients.
abstract: OBJECTIVE
  To evaluate the incidence and risk factors for grade 3 or 4 ALT or AST elevations (TE) and grade 4 total bilirubin elevations (TBE) among HIV/HCV- coinfected treatment-naïve patients with an initial regimen including 2 nucleoside analogs plus efavirenz (EFV), nevirapine (NVP), or a ritonavir-boosted protease inhibitor (PI/r).
  
  
  METHODS
  This was a retrospective multicenter observational cohort study that recruited 745 HIV-infected drug-naïve patients with detectable plasma HCV RNA who started a regimen including EFV, NVP, or PI/r.
  
  
  RESULTS
  EFV was prescribed in 323 (43%), NVP in 126 (17%), and a PI/r in 296 (40%) patients. Grade 3 or 4 TE were observed in 19 (5.9%) individuals receiving EFV compared with 14 (11%) on NVP (P = .056) and 31 (10.5%) on PI/r (P = .036). Grade 4 TBE were identified in 7 (2.2%) patients on EFV, 1 (0.8%) on NVP, and 11 (3.7%) on PI/r (P = .19). Therapy was discontinued due to liver toxicity in 13 (4%) patients on EFV, 16 (13%) on NVP, and 17 (6%) on PI/r (P = .003).
  
  
  CONCLUSIONS
  Regimens including EFV, NVP, or PI/r are generally safe in treatment-naïve HIV/HCV-coinfected patients. Grade 3-4 TE are less commonly seen with EFV than with PI/r. Discontinuations due to hepatotoxicity were less frequent for patients receiving EFV than for those treated with NVP.
authors.affiliation: Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Macías
authors.forename: Karin
authors.initials: K
authors.lastname: Neukam
authors.forename: Josep
authors.initials: J
authors.lastname: Mallolas
authors.forename: Luis F
authors.initials: LF
authors.lastname: López-Cortés
authors.forename: José A
authors.initials: JA
authors.lastname: Cartón
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.forename: José A
authors.initials: JA
authors.lastname: Iribarren
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Manell
authors.initials: M
authors.lastname: Crespo
authors.forename: Ignacio
authors.initials: I
authors.lastname: de Los Santos
authors.forename: Enrique
authors.initials: E
authors.lastname: Ortega
authors.forename: Hernando
authors.initials: H
authors.lastname: Knobel
authors.forename: María J
authors.initials: MJ
authors.lastname: Jiménez-Expósito
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000145:classification; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D060085:Coinfection; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D019438:Ritonavir