title: Hepatic safety profile of raltegravir in HIV-infected patients with chronic hepatitis C.
abstract: BACKGROUND
  Patients with chronic hepatitis C virus (HCV) infection experience antiretroviral-associated liver toxicity more frequently than HIV mono-infected persons. Herein, we report the hepatic safety profile of raltegravir in a relatively large group of HIV/HCV co-infected patients, a population that was poorly represented in the registrational studies.
  
  
  METHODS
  Prospective, observational study of all antiretroviral-experienced HIV-infected patients who initiated raltegravir from January 2006 to January 2009 at a reference HIV clinic. Clinical data, laboratory parameters and liver stiffness measured at baseline, week 4 and every 3 months thereafter were collected. Chronic hepatitis C was defined as positive serum HCV-RNA. Grade 1-4 hepatotoxicity was defined following the AIDS Clinical Trials Group definition for liver enzyme elevations (LEEs). A control group of patients who initiated protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) was examined similarly.
  
  
  RESULTS
  Data from 218 HIV-infected patients on raltegravir were analysed, 126 HIV mono-infected and 92 HIV/HCV co-infected patients. Any degree of LEEs occurred in 10 (7.9%) HIV mono-infected and 23 (25%) co-infected patients (relative risk 3.1; 95% confidence interval 2.9-3.4; P = 0.002). Severe hepatotoxicity (grade 3-4), however, was only seen in 3 (1.4%) patients, all co-infected with HCV. It occurred at months 1, 15 and 15, respectively. In all three subjects other reasons than raltegravir exposure most likely explained LEEs. Multivariate analysis revealed HCV co-infection as the only independent variable associated with any degree of hepatotoxicity on raltegravir (P = 0.03). Finally, the rate of LEEs in patients on raltegravir was lower than in those who were treated with PIs or NNRTIs.
  
  
  CONCLUSIONS
  LEEs are less frequent in patients treated with raltegravir than with other antiretroviral drug classes. However, HIV/HCV co-infected patients treated with raltegravir experienced LEEs more frequently than HIV mono-infected persons. In this series, LEEs in patients treated with raltegravir were uniformly mild and no cases of grade 3-4 hepatotoxicity could be directly attributed to the drug. These results reinforce the overall hepatic safety profile of raltegravir.
authors.affiliation: Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Vispo
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mena
authors.forename: Ivana
authors.initials: I
authors.lastname: Maida
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco
authors.forename: Mateo
authors.initials: M
authors.lastname: Cordoba
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.forename: Sonia
authors.initials: S
authors.lastname: Rodriguez-Novoa
authors.forename: Elena
authors.initials: E
authors.lastname: Alvarez
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Jimenez-Nacher
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000009:adverse effects* / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D012720:Severity of Illness Index
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium