title: Liver tolerance of raltegravir-containing antiretroviral therapy in HIV-infected patients with chronic hepatitis C.
abstract: OBJECTIVE
  To evaluate the liver safety of raltegravir-including combinations in HIV/hepatitis C virus (HCV) co-infected patients.
  
  
  METHODS
  Grade 3-4 transaminase elevations (TEs) and grade 4 total bilirubin elevations (TBEs) were assessed during 12 months in 108 HIV/HCV co-infected patients starting antiretroviral therapy including raltegravir in a retrospective cohort study. Furthermore, the relationship between baseline fibrosis and hepatotoxic events was determined.
  
  
  RESULTS
  Eight patients (7.4%) developed grade 3 TEs and two (1.9%) patients showed grade 4 TEs. TBE grade 4 was detected in two (1.9%) patients. No patient permanently discontinued raltegravir because of hepatotoxic events. Of the patients with and without significant fibrosis, six (9.4%) and two (11.8%), respectively, showed grade 3-4 TEs (P = 0.769). Grade 3-4 TEs was observed in four (9.8%) patients in whom cirrhosis was ruled out, while none of the patients diagnosed with cirrhosis developed grade 3-4 TEs (P = 0.303). During the follow-up, the median (Q1-Q3) CD4 cell count increased from 257 (145-421) cells/mm(3) to 407 (213-587) cells/mm(3) (P < 0.0001) and the number of patients with an undetectable HIV viral load augmented from 33 (30.6%) to 73 (81.1%) (P = 0.002).
  
  
  CONCLUSIONS
  Raltegravir-containing regimens are safe in HIV/HCV co-infected patients. The incidence of severe liver toxicity of raltegravir in these individuals is in the range of boosted protease inhibitors in clinical trials. The frequencies of grade 3-4 TEs and grade 4 TBEs were similar in patients receiving raltegravir with or without significant fibrosis or cirrhosis.
authors.affiliation: Infectious Diseases Unit, 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: Joaquín
authors.initials: J
authors.lastname: Portilla
authors.forename: José A
authors.initials: JA
authors.lastname: Iribarren
authors.forename: Ignacio
authors.initials: I
authors.lastname: de Los Santos
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.forename: Manuel
authors.initials: M
authors.lastname: Márquez
authors.forename: Marcial
authors.initials: M
authors.lastname: Delgado
authors.forename: Francisco
authors.initials: F
authors.lastname: Téllez
authors.forename: Dolores
authors.initials: D
authors.lastname: Merino
authors.forename: Livia
authors.initials: L
authors.lastname: Giner
authors.forename: Miguel A
authors.initials: MA
authors.lastname: von Wichmann
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods; D001663:Bilirubin / Q000097:blood; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects*; D000068898:Raltegravir Potassium; D012189:Retrospective Studies; D000637:Transaminases / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D000637:Transaminases; D001663:Bilirubin