title: Pharmacokinetic study of raltegravir in HIV-infected patients with end-stage liver disease: the LIVERAL-ANRS 148 study.
abstract: BACKGROUND
  The end-stage LIVER disease and RALtegravir-Agence Nationale de Recherche sur le Sida et les hépatites (LIVERAL-ANRS) 148 study aimed to evaluate the safety, efficacy, and pharmacokinetic parameters of raltegravir (RAL) in human immunodeficiency virus (HIV)-infected patients with end-stage liver disease (ESLD) (substudy 1) and to assess the lack of pharmacokinetic interaction between RAL and the immunosuppressive regimen introduced after liver transplant (substudy 2).
  
  
  METHODS
  All patients received 400 mg RAL twice daily plus 2 nucleoside reverse transcriptase inhibitors. Liver function and immunovirological parameters were monitored throughout the study. Serial blood samples were drawn to explore RAL pharmacokinetics. Plasma concentrations of protein unbound, total RAL, and RAL glucuronide were determined by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  Ten patients with ESLD were analyzed in substudy 1. Despite an increased RAL exposure, RAL was well tolerated in all patients and no patient had to stop RAL therapy because of adverse events. Four patients were analyzed in substudy 2. No pharmacokinetic interaction was observed between cyclosporine, mycophenolic acid, and RAL. RAL tolerability was excellent; there were no episodes of acute rejection or opportunistic infection. HIV-RNA levels remained controlled and CD4 cell counts remained stable in all patients throughout the study.
  
  
  CONCLUSIONS
  The results of the substudy 1 support RAL administration to patients with ESLD. Substudy 2 assesses the safety, tolerability, and efficacy of RAL therapy in HIV-infected patients after liver transplant. RAL might be recommended as a suitable antiretroviral therapy in HIV-infected patients undergoing liver transplant.
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Service de Pharmacie Clinique et Pharmacocinétique, Le Kremlin-Bicêtre Département Hospitalo, Universitaire Hepatinov.
authors.forename: Caroline
authors.initials: C
authors.lastname: Barau
authors.affiliation: INSERM SC10-US019.
authors.forename: Joséphine
authors.initials: J
authors.lastname: Braun
authors.affiliation: INSERM SC10-US019.
authors.forename: Corine
authors.initials: C
authors.lastname: Vincent
authors.affiliation: Département Hospitalo, Universitaire Hepatinov AP-HP, Hôpital Paul Brousse, Service de Virologie, Villejuif.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Haim-Boukobza
authors.affiliation: AP-HP, Hôpital Saint-Louis, Service des Maladies Infectieuses et Tropicales et INSERM U941, Université Paris VII Denis Diderot.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.affiliation: Hospices Civils de Lyon, Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse et INSERM U1052.
authors.forename: Patrick
authors.initials: P
authors.lastname: Miailhes
authors.affiliation: INSERM SC10-US019.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fournier
authors.affiliation: INSERM SC10-US019.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aboulker
authors.affiliation: Département Hospitalo, Universitaire Hepatinov AP-HP, Hôpital Bicêtre, Service de Médecine Interne et Maladies Infectieuses, Le Kremlin-Bicêtre.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vittecoq
authors.affiliation: Département Hospitalo, Universitaire Hepatinov AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire et INSERM UMR-S785 Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Duclos-Vallée
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Service de Pharmacie Clinique et Pharmacocinétique, Le Kremlin-Bicêtre Département Hospitalo, Universitaire Hepatinov.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Taburet
authors.affiliation: Département Hospitalo, Universitaire Hepatinov AP-HP, Hôpital Bicêtre, Service de Médecine Interne et Maladies Infectieuses, Le Kremlin-Bicêtre.
authors.forename: Elina
authors.initials: E
authors.lastname: Teicher
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D064420:Drug-Related Side Effects and Adverse Reactions; D058625:End Stage Liver Disease; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium
keywords: HIV; end-stage liver disease; liver transplant; pharmacokinetics; raltegravir