title: Incidence and risk factors for liver enzymes elevations in highly treatment-experienced patients switching from enfuvirtide to raltegravir: a sub-study of the ANRS-138 EASIER trial.
abstract: In the ANRS EASIER trial where treatment-experienced patients switched from enfuvirtide (ENF) to raltegravir (RAL), a high incidence of transaminase elevation was reported in the RAL arm.
  
  
  
  We compared the incidence of emergent liver enzyme elevations (LEE) of grade 2 or more among patients randomized to the maintenance ENF arm or the switch RAL arm up to W24. We also assessed the overall incidence of LEE over the 48-week duration of the trial and baseline risk factors for grade 2 or more alanine aminotransferase (ALT) elevation using univariate and multivariate analyses.
  
  
  
  During the first 24 weeks, 6/84 (7.1 %) and 2/85 patients (2.4 %) presented with ALT elevation of grade 2 or more in the RAL and ENF arms, respectively (p = 0.21). Grade 2 or more γGT and ALP elevations were seen in 18 and 11 % (p = 0.35), and 5 and 1 % (p = 0.14) of patients in the RAL and ENF arms, respectively. The 48-week incidence of grade 2 or more LEE was 11.6 per 100-pts-years for ALT, 24.5 per 100-pts-years for γ-GT and 4.5 per 100-pts-years for ALP, respectively. In the multivariate analysis, tipranavir/ritonavir use (OR 3.66; 95 % CI [1.20-11.1], p = 0.022) and elevated ALT at baseline (OR 10.3; 95 % CI [2.67-39.6], p < 10(-3)) were significantly associated with a grade 2 or more ALT elevation during follow-up.
  
  
  
  The incidence of LEE was relatively high in these highly treatment-experienced patients switching to a RAL-based regimen. Both tipranavir/ritonavir use and high baseline ALT levels were associated with an increased risk of ALT.
  
  
  
  ClinicalTrials.gov identifier: NCT00454337.
authors.affiliation: Department of Infectious Diseases, Assistance Publique Hôpitaux de Paris, Saint-Louis Hospital, University of Paris Diderot Paris 7, 1 avenue Claude Vellefaux, 75010 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: de Castro
authors.affiliation: INSERM SC10-US019, Villejuif, France.
authors.forename: Joséphine
authors.initials: J
authors.lastname: Braun
authors.affiliation: INSERM SC10-US019, Villejuif, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Charreau
authors.affiliation: Department of Infectiology and Hematology, Font-Pré Hospital, Toulon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lafeuillade
authors.affiliation: Department of Infectious Diseases, Hôtel-Dieu Hospital, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Viard
authors.affiliation: Department of Infectious Diseases, Hôtel-Dieu Hospital, Nantes, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Allavena
authors.affiliation: INSERM SC10-US019, Villejuif, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aboulker
authors.affiliation: Department of Infectious Diseases, Assistance Publique Hôpitaux de Paris, Saint-Louis Hospital, University of Paris Diderot Paris 7, 1 avenue Claude Vellefaux, 75010 Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D057915:Drug Substitution / Q000009:adverse effects*; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects* / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects* / Q000627:therapeutic use; D000068898:Raltegravir Potassium / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D019428:HIV Integrase Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide; D000068898:Raltegravir Potassium; D000410:Alanine Transaminase
keywords: Liver enzymes; Raltegravir; Tipranavir; Transaminases