title: Triple therapy with boceprevir or telaprevir in a European cohort of cirrhotic HIV/HCV genotype 1-coinfected patients.
abstract: OBJECTIVE
  The efficacy and safety of triple therapy combining boceprevir (BOC) or telaprevir (TVR) with pegylated interferon-alfa and ribavirin (PegIFN/RBV) has rarely been investigated in human immunodeficiency virus/hepatitis C virus (HIV/HCV) genotype 1-coinfected patients with cirrhosis.
  
  
  METHODS
  We conducted a European (France, Italy, Germany, Netherlands) multicentre study of triple therapy in cirrhotic HIV/HCV GT1-coinfected patients.
  
  
  RESULTS
  Fifty-nine patients (47 TVR, 12 BOC) were studied. Median CD4 cell count was 457 (293-578)/mm(3), and HIV viral load was <50 copies/ml in 93% of patients. The HCV genotype was GT1a (78%) or GT1b (13%). Previous PegIFN/RBV therapy had resulted in non-response (73%) or relapse (12%), and 15% of patients were treatment-naïve. The sustained virological response rate at week 12 (SVR12) was 53% overall (57% with TVR, 36% with BOC). A baseline HCV-RNA level <800 000 IU/ml tended to be associated with SVR12 (65 vs 42%, P = 0.11). In multivariate analysis, a virological response at week 4 after BOC or TVR initiation was significantly associated with SVR12 (P = 0.040). Early discontinuation of triple therapy was frequent (n = 26, 44%), because of non-response/breakthrough (65%) or adverse events (AEs) (35%). Three patients died. Severe anaemia (<9 g/dl) occurred in 14 patients (25%), leading to RBV dose reduction (22%), erythropoietin use (56%) or blood transfusion (14%). In multivariate analysis, lack of RBV dose reduction was significantly associated with severe AEs (P = 0.006).
  
  
  CONCLUSIONS
  More than half of HIV/HCV GT1-coinfected patients with cirrhosis achieved a SVR12. To avoid unnecessary adverse effects, therapy should be discontinued if no response is obtained at week 4.
authors: Department of Infectious and Tropical Diseases, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France.
authors: Patrick
authors: P
authors: Miailhes
authors: Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France.
authors: Camille
authors: C
authors: Gilbert
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.|Department of Infectious and Tropical Diseases, Saint-Antoine Hospital, AP-HP, Paris, France.
authors: Karine
authors: K
authors: Lacombe
authors: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht (UMCU), Utrecht, the Netherlands.
authors: Joop E
authors: JE
authors: Arends
authors: Infectious Diseases Department, AO Niguarda Ca' Granda, Milano, Italy.
authors: Massimo
authors: M
authors: Puoti
authors: Infectious Diseases Department, University of Bonn, Bonn, Germany.
authors: Jürgen K
authors: JK
authors: Rockstroh
authors: Hepatology Unit, Cochin Hospital, AP-HP, Paris, France.|Paris and Cochin Institute, INSERM-U1016, Paris-Descartes University, Paris, France.
authors: Philippe
authors: P
authors: Sogni
authors: Hepatology Unit, Cochin Hospital, AP-HP, Paris, France.|Paris and Cochin Institute, INSERM-U1016, Paris-Descartes University, Paris, France.
authors: Hélène
authors: H
authors: Fontaine
authors: Department of Internal Medicine, CHU de Nice, Archet Hospital, University of Nice Sophia Antipolis, Nice, France.
authors: Eric
authors: E
authors: Rosenthal
authors: Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France.
authors: Maria
authors: M
authors: Winnock
authors: Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France.
authors: Marc-Arthur
authors: MA
authors: Loko
authors: Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France.|CHU de Bordeaux, Pôle de Santé Publique, Service d'Information Médicale, Bordeaux, France.
authors: Linda
authors: L
authors: Wittkop
authors: Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France.|CHU de Bordeaux, Pôle de Santé Publique, Service d'Information Médicale, Bordeaux, France.
authors: François
authors: F
authors: Dabis
authors: Department of Internal Medicine and Infectious Diseases, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.
authors: Dominique
authors: D
authors: Salmon
mesh_terms: D000740:Anemia; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D060085:Coinfection / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D005838:Genotype; D005858:Germany; D015658:HIV Infections / Q000188:drug therapy*; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007558:Italy; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009842:Oligopeptides / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D012254:Ribavirin; 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
keywords: HIV/HCV genotype 1 coinfection; boceprevir; cirrhosis; telaprevir