title: Hepatitis C virus drug resistance-associated substitutions: State of the art summary.
abstract: Hepatitis C virus (HCV) drug development has resulted in treatment regimens composed of interferon-free, all-oral combinations of direct-acting antivirals. While the new regimens are potent and highly efficacious, the full clinical impact of HCV drug resistance, its implications for retreatment, and the potential role of baseline resistance testing remain critical research and clinical questions. In this report, we discuss the viral proteins targeted by HCV direct-acting antivirals and summarize clinically relevant resistance data for compounds that have been approved or are currently in phase 3 clinical trials.
  
  
  CONCLUSIONS
  This report provides a comprehensive, systematic review of all resistance information available from sponsors' trials as a tool to inform the HCV drug development field.
authors.affiliation: Forum for Collaborative HIV Research, University of California at Berkeley, Washington, DC.
authors.forename: Erik
authors.initials: E
authors.lastname: Lontok
authors.affiliation: Center for Drug Evaluation and Research, Office of Antimicrobial Products, Division of Antiviral Products, US Food and Drug Administration, Silver Spring, MD.
authors.forename: Patrick
authors.initials: P
authors.lastname: Harrington
authors.affiliation: Merck Research Laboratories, West Point, PA.
authors.forename: Anita
authors.initials: A
authors.lastname: Howe
authors.affiliation: Vertex Pharmaceuticals, Inc., Boston, MA.
authors.forename: Tara
authors.initials: T
authors.lastname: Kieffer
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Lennerstrand
authors.affiliation: Janssen Infectious Diseases, Beerse, Belgium.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Bristol-Myers Squibb Research and Development, Wallingford, CT.
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mo
authors.affiliation: Data First Consulting, Inc., Belmont, CA.
authors.forename: Neil
authors.initials: N
authors.lastname: Parkin
authors.affiliation: AbbVie, Inc., Chicago, IL.
authors.forename: Tami
authors.initials: T
authors.lastname: Pilot-Matias
authors.affiliation: Forum for Collaborative HIV Research, University of California at Berkeley, Washington, DC.
authors.forename: Veronica
authors.initials: V
authors.lastname: Miller
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D055808:Drug Discovery; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C080107:NS4B protein, flavivirus