Hepatitis C virus drug resistance associated substitutions and their clinical relevance: Update 2018

Drug Resist Updat. 2018 Mar;37:17-39. doi: 10.1016/j.drup.2018.01.004. Epub 2018 Feb 21.


Nowadays, due to the development of potent Direct-Acting Antiviral Agents (DAAs) that specifically target NS3, NS5A and NS5B viral proteins, several new and highly efficacious options to treat chronic Hepatitis C virus (HCV) infection are available. The natural presence of resistance associated substitutions (RASs), as well as their rapid emergence during incomplete drug-pressure, are intrinsic characteristics of HCV that greatly affect treatment outcome and the chances to achieve a virolgical cure. To date, a high number of RASs in NS3, NS5A, and NS5B have been associated in vivo and/or in vitro with reduced susceptibility to DAAs, but no comprehensive RASs list is available. This review thus provides an updated, systematic overview of the role of RASs to currently approved DAAs or in phase II/III of clinical development against HCV-infection, discriminating their impact in different HCV-genotypes and DAAs, providing assistance for a fruitful use of HCV resistance testing in clinical practice.

Keywords: Direct acting antiviral agents; Fold-change; HCV genotypic resistance testing; HCV sequencing; Treatment failure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • Drug Design
  • Drug Resistance, Viral* / genetics
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Molecular Targeted Therapy
  • Mutation
  • Treatment Failure
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism


  • Antiviral Agents
  • NS-5 protein, hepatitis C virus
  • NS3 protein, hepatitis C virus
  • Viral Nonstructural Proteins