title: Faldaprevir and pegylated interferon α-2a/ribavirin in individuals co-infected with hepatitis C virus genotype-1 and HIV.
abstract: OBJECTIVE
  Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. STARTVerso4 assessed the efficacy and safety of faldaprevir and response-guided pegylated interferon α-2a/ribavirin (PegIFN/RBV) in individuals with HCV/HIV co-infection.
  
  
  METHODS
  A phase 3 open-label study (NCT01399619).
  
  
  METHODS
  Individuals (N = 308) co-infected with HCV genotype 1 (treatment-naive or prior interferon relapsers) and HIV [96% on antiretroviral therapy (ART)] received faldaprevir 120 mg (N = 123) or 240 mg (N = 185) and PegIFN/RBV. Those receiving a protease inhibitor or efavirenz ART were assigned to faldaprevir 120 or 240 mg, respectively. Individuals achieving early treatment success (ETS; HCV RNA <25 IU/ml at week 4 and undetectable at week 8) were randomized to 24 or 48 weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12).
  
  
  RESULTS
  SVR12 was achieved in 221 (72%) individuals, and the rates were comparable across faldaprevir doses. ETS was achieved in 80%, and of these 86% achieved SVR12, with comparable rates with 24 and 48 weeks of PegIFN/RBV (87 and 94%, respectively). In multivariate analysis, age below 40 years, IL28B CC genotype, and baseline HCV RNA below 800 000 IU/ml were associated with SVR12 (P = 0.027, P < 0.0001, and P = 0.0002, respectively), whereas treatment (ART regimen and faldaprevir dose), liver cirrhosis, and genotype 1 subtype were not. The safety profile was comparable to that of faldaprevir in HCV-monoinfected individuals.
  
  
  CONCLUSIONS
  High SVR12 rates were achieved with faldaprevir and PegIFN/RBV in HIV/HCV co-infected individuals, regardless of faldaprevir dose and background ART, HCV genotype 1 subtype, or cirrhosis status. SVR rates mirrored those obtained with similar regimens in HCV monoinfected individuals.
authors.affiliation: aIcahn School of Medicine at Mount Sinai, New York, USA bChelsea and Westminster Hospital, London, UK cHospital Carlos III, Madrid, Spain dEPIMED, Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany eHospital de la Santa Creu i Sant Pau, Barcelona, Spain fUniversity of Bonn, Bonn, Germany gRoyal Free Hospital, London, UK hHospital Clínic iHospital Universitari Germans Trias i Pujol and Universitat Autònoma de Barcelona, Barcelona, Spain jMedizinisches Infektiologiezentrum Berlin (MIB), Berlin, Germany kUT Southwestern Medical Center, Dallas, Texas lBoehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA mBoehringer Ingelheim España S.A., Barcelona, Spain.
authors.forename: Douglas
authors.initials: D
authors.lastname: Dieterich
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.forename: Keikawus
authors.initials: K
authors.lastname: Arastéh
authors.forename: Josep M
authors.initials: JM
authors.lastname: Guardiola
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bhagani
authors.forename: Montserrat
authors.initials: M
authors.lastname: Laguno
authors.forename: Cristina
authors.initials: C
authors.lastname: Tural
authors.forename: Patrick
authors.initials: P
authors.lastname: Ingiliz
authors.forename: Mamta K
authors.initials: MK
authors.lastname: Jain
authors.forename: Jerry O
authors.initials: JO
authors.lastname: Stern
authors.forename: Montserrat
authors.initials: M
authors.lastname: Manero
authors.forename: Richard
authors.initials: R
authors.lastname: Vinisko
authors.forename: Jens
authors.initials: J
authors.lastname: Kort
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000621:Aminoisobutyric Acids; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007930:Leucine / Q000031:analogs & derivatives; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives; D011804:Quinolines; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000175:diagnosis; D055815:Young Adult
chemical_list: D000621:Aminoisobutyric Acids; D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011804:Quinolines; D011994:Recombinant Proteins; D013844:Thiazoles; D011092:Polyethylene Glycols; D012254:Ribavirin; C552340:faldaprevir; D011392:Proline; D007930:Leucine; C100416:peginterferon alfa-2a