title: The impact of interleukin 28B rs12979860 single nucleotide polymorphism and liver fibrosis stage on response-guided therapy in HIV/HCV-coinfected patients.
abstract: OBJECTIVE
  According to the European AIDS Clinical Society (EACS) guidelines for response-guided therapy (RGT) of chronic hepatitis C virus (HCV) infection in HIV-positive patients, HCV-genotype (GT) and rapid virologic response (RVR) exclusively determine the duration of antiviral therapy with pegylated interferon and ribavirin (PEGIFN+RBV). The aim of this study was to investigate the impact of interleukin 28B rs12979860 single nucleotide polymorphism (IL28B) and liver fibrosis stage on RGT in HIV/HCV-coinfected patients.
  
  
  METHODS
  Four hundred and thirty HIV/HCV-coinfected patients treated with PEGIFN+RBV were included in this multinational, retrospective analysis.
  
  
  METHODS
  Advanced liver fibrosis was defined as either METAVIR F3/F4 or liver stiffness more than 9.5 kPa.
  
  
  RESULTS
  In patients with GT1/4 without RVR (GT1/4-noRVR), higher sustained virologic response (SVR) rates were observed in patients with extended treatment duration (48 weeks: 35% vs. 72 weeks: 60%; P = 0.008). In GT1/4-noRVR patients without advanced liver fibrosis (48 weeks: 45% vs. 72 weeks: 61%; P = 0.176), or with IL28B C/C (48 weeks: 48% vs. 72 weeks: 69%; P = 0.207), SVR rates did not vary significantly throughout the treatment duration subgroups. In contrast, in patients with advanced liver fibrosis (48 weeks: 11% vs. 72 weeks: 45%; P = 0.031), or IL28B non-C/C (48 weeks: 28% vs. 72 weeks: 56%; P = 0.011), extended treatment duration was associated with substantially higher SVR rates. GT2/3 patients with RVR (GT2/3-RVR) with shortened treatment duration (24 weeks) displayed SVR rates ranging from 83 to 100%, regardless of IL28B and liver fibrosis stage.
  
  
  CONCLUSIONS
  Our study confirms the concept of RGT in HIV/HCV coinfection and supports the extension of therapy duration to 72 weeks for patients with GT1/4-noRVR, especially in patients with IL28B non-C/C or advanced liver fibrosis. The results of our study strongly support the shortening of therapy duration to 24 weeks in GT2/3-RVR patients, regardless of IL28B and advanced liver fibrosis.
authors.affiliation: aDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria bUnit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville cDepartment of Infectious Diseases, Hospital Universitario Reina Sofía, Córdoba, Spain dDepartment of Infectious Diseases, AO Ospedale Niguarda Ca' Granda, Milano, Italy eDepartment of Internal Medicine I, University of Bonn, Bonn fPraxis Driesener Strasze, Berlin, Germany gDepartment of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland hDepartment of Dermatology, Medical University of Innsbruck, Innsbruck, Austria iDepartment of Clinical Immunology and Rheumatology, Medical University Hannover, Hannover, Germany.
authors.forename: Mattias
authors.initials: M
authors.lastname: Mandorfer
authors.forename: Karin
authors.initials: K
authors.lastname: Neukam
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiberger
authors.forename: Berit A
authors.initials: BA
authors.lastname: Payer
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.forename: Christoph
authors.initials: C
authors.lastname: Boesecke
authors.forename: Axel
authors.initials: A
authors.lastname: Baumgarten
authors.forename: Anna
authors.initials: A
authors.lastname: Grzeszczuk
authors.forename: Robert
authors.initials: R
authors.lastname: Zangerle
authors.forename: Dirk
authors.initials: D
authors.lastname: Meyer-Olson
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D060085:Coinfection / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda