title: Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.
abstract: There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.
authors.affiliation: Plymouth University, Peninsula School of Medicine and Dentistry, Plymouth PL6 8BU, UK. asmaahmed1@nhs.net.
authors.forename: Asma
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Plymouth University, Peninsula School of Medicine and Dentistry, Plymouth PL6 8BU, UK. daniel.felmlee@plymouth.ac.uk.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Felmlee
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D009154:Mutation; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents
keywords: breakthrough variants; direct acting antivirals; hepatitis C; resistance