Caroline Barau1, Joséphine Braun2, Corine Vincent2, Stéphanie Haim-Boukobza3, Jean-Michel Molina4, Patrick Miailhes5, Isabelle Fournier2, Jean-Pierre Aboulker2, Daniel Vittecoq6, Jean-Charles Duclos-Vallée7, Anne-Marie Taburet1, Elina Teicher6. 1. Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Service de Pharmacie Clinique et Pharmacocinétique, Le Kremlin-Bicêtre Département Hospitalo, Universitaire Hepatinov. 2. INSERM SC10-US019. 3. Département Hospitalo, Universitaire Hepatinov AP-HP, Hôpital Paul Brousse, Service de Virologie, Villejuif. 4. AP-HP, Hôpital Saint-Louis, Service des Maladies Infectieuses et Tropicales et INSERM U941, Université Paris VII Denis Diderot. 5. Hospices Civils de Lyon, Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse et INSERM U1052. 6. Département Hospitalo, Universitaire Hepatinov AP-HP, Hôpital Bicêtre, Service de Médecine Interne et Maladies Infectieuses, Le Kremlin-Bicêtre. 7. Département Hospitalo, Universitaire Hepatinov AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire et INSERM UMR-S785 Villejuif, France.
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.
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)-infectedpatients 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 RALglucuronide 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-infectedpatients after liver transplant. RAL might be recommended as a suitable antiretroviral therapy in HIV-infectedpatients undergoing liver transplant.
Authors: Isabel Campos-Varela; Jennifer L Dodge; Marina Berenguer; René Adam; Didier Samuel; Fabrizio Di Benedetto; Vincent Karam; Luca S Belli; Christophe Duvoux; Norah A Terrault Journal: Transplantation Date: 2020-10 Impact factor: 5.385