title: Future of hepatitis C therapy:  development of direct-acting antivirals.
abstract: OBJECTIVE
  The landscape of hepatitis C virus (HCV) therapy will change considerably over the next decade with the probable licensure of many HCV direct-acting antiviral (DAA) therapy agents. This review will outline the data on the initial two DAA agents licensed (protease inhibitors telaprevir and boceprevir) and cover potential future therapeutic strategies and challenges for DAA-based therapy, including in the context of HIV/HCV coinfection.
  
  
  RESULTS
  Phase III trials evaluating the addition of telaprevir or boceprevir to pegylated interferon and ribavirin in both HCV treatment naïve and experienced populations with chronic HCV genotype 1 have demonstrated considerable improvements in sustained virological response, with many patients able to shorten total treatment duration from 48 to 24-36 weeks. Although these initial DAA-based treatment results are encouraging, additional toxicity, problematic dosing schedules, and potential drug-drug interactions pose challenges for clinical management, particularly in HIV/HCV coinfection. Phase II trials with telaprevir and boceprevir in HIV/HCV populations are underway. Subsequent DAA agents appear to have improved tolerability and dosing schedules and open the door for interferon (IFN)-free DAA-based combination therapy.
  
  
  CONCLUSIONS
  Development of DAA therapy will lead to a major shift in HCV clinical management, particularly with the potential for IFN-free combination therapy.
authors: Viral Hepatitis Clinical Research Program, The Kirby Institute, The University of New South Wales, Australia. gdore@kirby.unsw.edu.au
authors: Gregory J
authors: GJ
authors: Dore
authors: Gail V
authors: GV
authors: Matthews
authors: Jürgen
authors: J
authors: Rockstroh
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000150:complications; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
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