title: Strategies for assignment of HIV-HCV genotype-1-coinfected patients to either dual-therapy or direct-acting antiviral agent-based triple-therapy.
abstract: BACKGROUND
  The aim of this study was to evaluate strategies for assignment of HIV-HCV genotype-1-coinfected patients (HIV-HCV-GT1) to either dual-therapy or direct-acting antiviral agent (DAA)-based triple-therapy.
  
  
  METHODS
  A total of 148 treatment-naive HIV-HCV-GT1 who received antiviral therapy with pegylated interferon/ribavirin were included in this multinational, retrospective analysis. Patients with rapid virological response (RVR) were treated for 48 weeks, while patients without RVR received either 48 or 72 weeks of treatment. IL28B rs12979860 (IL28B) non-C/C, advanced liver fibrosis and high HCV RNA were considered as established risk factors for treatment failure.
  
  
  RESULTS
  A trend toward higher sustained virological response (SVR) rates in patients with IL28B C/C (65% [37/57] versus 51% [40/79]; P=0.097) was observed. Higher SVR rates were observed in patients without advanced liver fibrosis (61% [47/77] versus 42% [22/52]); P=0.036) and without high HCV RNA (73% [35/48] versus 49% [49/100]; P=0.006), as well as in patients with RVR (90% [35/39] versus 45% [49/109]; P<0.001). SVR rates varied statistically significantly between the risk factors for treatment failure subgroups (86% [6/7] versus 69% [34/49] versus 48% [21/44] versus 20% [4/20] for zero, one, two and three risk factors, respectively; P<0.001). In patients without RVR, higher rates of SVR were observed in those treated for 72 weeks (62% [23/37]), when compared to patients treated for 48 weeks (36% [26/72]; P=0.01).
  
  
  CONCLUSIONS
  RVR had an excellent positive predictive value for the response to dual-therapy in HIV-HCV-GT1, emphasizing the utility of a lead-in phase for assigning these patients to dual-therapy or DAA-based triple-therapy. The use of an IL28B-guided approach was suboptimal, while a combination of established baseline predictors may provide guidance for individual treatment decisions prior to the initiation of antiviral therapy. However, the extension of treatment duration to 72 weeks in HIV-HCV-GT1 without RVR should be strongly considered if triple-therapy is not available.
authors.affiliation: Vienna HIV & Liver Study Group, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Mattias
authors.initials: M
authors.lastname: Mandorfer
authors.forename: Karin
authors.initials: K
authors.lastname: Neukam
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: Diana
authors.initials: D
authors.lastname: Ernst
authors.forename: Jürgen Kurt
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Pineda
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiberger
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D060085:Coinfection; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008103:Liver Cirrhosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a