title: Early virological assessment during telaprevir- or boceprevir-based triple therapy in hepatitis C cirrhotic patients who failed a previous interferon based regimen - The ANRS CO20-CUPIC study.
abstract: OBJECTIVE
  To assess within the ANRS CO20-CUPIC cohort whether the viral load (VL) at week 2/week 6 for telaprevir/boceprevir-based triple therapy, respectively, was predictive of sustained virological response (SVR) in patients with hepatitis C virus (HCV) infection and to study the relevance of this measurement to early diagnose drug resistance.
  
  
  METHODS
  Observational study of HCV genotype 1 patients with compensated cirrhosis (Child-Pugh A), non-responders to a prior course of interferon (IFN)-based therapy and who started triple therapy. Patients received either 12 weeks of telaprevir in combination with PEG-IFN/ribavirin (RBV), then 36 weeks of PEG-IFN/RBV, or 4 weeks of PEG-IFN/RBV, then 44 weeks of PEG-IFN/RBV and boceprevir.
  
  
  RESULTS
  A total of 262 patients were analyzed. For telaprevir-treated patients, 28% had undetectable VL at W2 of whom 81% achieved SVR12 whereas 67% had undetectable VL at W4 of whom 67% achieved SVR12. For boceprevir-treated patients 20% had undetectable VL at W6 and 86% of them achieved SVR12 whereas 36% had undetectable VL at W8 among whom 73% achieved SVR12. Five telaprevir-treated patients had a VL increase between W2 and W4 after a decrease between D0 and W2. Four of them did not achieve SVR12. Similarly, six boceprevir-treated patients had a VL increase between W6 and W8 after a decrease between D0 and W6. Five did not reach SVR12.
  
  
  CONCLUSIONS
  The assessment of HCV RNA level after two weeks of triple therapy in cirrhotic non-responder patients is a good predictor of SVR. This assessment was useful to do an early diagnosis of viral breakthrough.
authors: Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, 69004 Lyon, France; Inserm U1052, 69003 Lyon, France; Université Lyon I, 69622 Villeurbanne, France.
authors: François
authors: F
authors: Bailly
authors: Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, 69004 Lyon, France; École Normale Supérieure, 69007 Lyon, France.
authors: Victor
authors: V
authors: Virlogeux
authors: Inserm UMR-S 707, Université Pierre-et-Marie-Curie Paris 6, 75012 Paris, France.
authors: Cécilie
authors: C
authors: Dufour
authors: Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, 69004 Lyon, France; Inserm U1052, 69003 Lyon, France; Université Lyon I, 69622 Villeurbanne, France.
authors: Pierre
authors: P
authors: Pradat
authors: Hépato-gastro-entérologie, CHU Henri-Mondor, 94010 Créteil, France.
authors: Christophe
authors: C
authors: Hézode
authors: Hépato-gastroentérologie, CHU de Montpellier, Hôpital Saint-Éloi, 34090 Montpellier, France.
authors: Dominique
authors: D
authors: Larrey
authors: Pôle Digestif, CHU Purpan, UMR 152, Université Toulouse 3, 31059 Toulouse, France.
authors: Laurent
authors: L
authors: Alric
authors: Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, 94870 Villejuif, France; Unité 785, Inserm, 94870 Villejuif, France; Université Paris-Sud, 94270 Le Kremlin-Bicêtre, France.
authors: Didier
authors: D
authors: Samuel
authors: Department of Hepatology and Gastroenterology, Hôpital Saint-Joseph, 13285 Marseille, France.
authors: Marc
authors: M
authors: Bourlière
authors: Pôle Digestif-Gastro-entérologie-Hépatologie, CHU Purpan, 31059 Toulouse, France.
authors: Sophie
authors: S
authors: Métivier
authors: Clinique universitaire d'Hépato-Gastroentérologie, CHRU Michallon, 38043 Grenoble, France.
authors: Jean-Pierre
authors: JP
authors: Zarski
authors: Hôpital Cochin, AP-HP, Université Paris-René Descartes, Inserm U1016, 75014 Paris, France.
authors: Hélène
authors: H
authors: Fontaine
authors: Fédération Hépatologie, CHU Dupuytren, 87042 Limoges, France.
authors: Véronique
authors: V
authors: Loustaud-Ratti
authors: Hépato-gastro-entérologie orienté en hépatologie, CHU Saint-Antoine, 75012 Paris, France.
authors: Lawrence
authors: L
authors: Serfaty
authors: Department of Hepatology and Gastroenterology, CHU de Nancy, Université de Lorraine, Inserm U954, 54500 Vandœuvre-lès-Nancy, France.
authors: Jean-Pierre
authors: JP
authors: Bronowicki
authors: Inserm UMR-S 707, Université Pierre-et-Marie-Curie Paris 6, 75012 Paris, France.
authors: Fabrice
authors: F
authors: Carrat
authors: Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, 69004 Lyon, France; Inserm U1052, 69003 Lyon, France; Université Lyon I, 69622 Villeurbanne, France. Electronic address: fabien.zoulim@inserm.fr.
authors: Fabien
authors: F
authors: Zoulim
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use; D012313:RNA / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D012313:RNA; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C100416:peginterferon alfa-2a