title: First-generation protease inhibitor-triple therapy: SVR 24, safety, and predictors of response in a large single center cohort.
abstract: OBJECTIVE
  Aim of this retrospective study was to analyze the efficacy, safety, and predictors of treatment success for first-generation-PI triple therapies, including either boceprevir or telaprevir, in a mono-centric "real-life" setting with respect to SVR 24.
  
  
  METHODS
  131 patients (102 patients telaprevir, 29 patients boceprevir) were treated. Of these, 33/131 patients were treatment naïve, 72/131 patients had been pretreated with PEG-IFN/RBV (PR) (thereof: 36 with non-response, 30 with relapse, 6 unknown), and 26/131 patients previously had received non-pegylated interferon. 96/131 patients were infected with HCV genotype 1b. 41/131 patients had liver cirrhosis.
  
  
  RESULTS
  95/131 (73%) patients achieved SVR 24. SVR rates for subgroups were: 26/33 (79%) for treatment naïve, 25/30 (83%) for PR-relapse, 20/36 (56%) for PR-non-response, 21/26 (81%) for non-PR pretreated patients, (26/41) 63% for patients with liver cirrhosis, 23/35 (66%) genotype 1a, 72/96 (75%) genotype 1b. Predictors of SVR 24 were eRVR and a negative viral load at PI-treatment week 4 (p < 0.0001), negative predictors were quantifiable HCV viral load at PI-treatment week 4 (p < 0.0001), baseline platelet count < 100/nl (p < 0.0001), and previous PR-non-response (p = 0.006). 33/131 (25%) patients discontinued treatment prematurely, of those 14/131 (11%) patients due to virological failure. Side effects were frequent (anemia 59/131 [45%], severe infections 6/131 [5%]).
  
  
  CONCLUSIONS
  According to our SVR 24 results, efficacy of PI-based triple therapy in our "real-life" cohort is comparable to the large multi-centric clinical trials. Pronounced side effects are frequent during therapy and often need complex therapeutic interventions. Since new DAA are available, it is open to discussion, if first-generation PI-triple therapy is no longer indicated at all.
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tübingen, Tübingen, Germany. christoph.werner@med.uni-tuebingen.de.
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Werner
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tübingen, Tübingen, Germany. caro-fra@web.de.
authors.forename: Carolin
authors.initials: C
authors.lastname: Franz
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tübingen, Tübingen, Germany. daniel.egetemeyr@med.uni-tuebingen.de.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Egetemeyr
authors.affiliation: Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany. robert.beck@med.uni-tuebingen.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Beck
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tübingen, Tübingen, Germany. nisar.malek@med.uni-tuebingen.de.
authors.forename: Nisar P
authors.initials: NP
authors.lastname: Malek
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tübingen, Tübingen, Germany. ulrich.lauer@uni-tuebingen.de.
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Lauer
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tübingen, Tübingen, Germany. christoph.berg@med.uni-tuebingen.de.
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Berg
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000008:administration & dosage*; D012189:Retrospective Studies
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D011480:Protease Inhibitors; 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