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Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

by Asma Ahmed 1,† and Daniel J. Felmlee 2,*,†
1
Plymouth University, Peninsula School of Medicine and Dentistry, Plymouth PL6 8BU, UK
2
Plymouth University, Peninsula School of Medicine and Dentistry, Plymouth PL6 8BU, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Thomas Baumert
Viruses 2015, 7(12), 6716-6729; https://doi.org/10.3390/v7122968
Received: 6 October 2015 / Revised: 24 November 2015 / Accepted: 8 December 2015 / Published: 18 December 2015
(This article belongs to the Special Issue HCV Drug Resistance)
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. View Full-Text
Keywords: resistance; hepatitis C; direct acting antivirals; breakthrough variants resistance; hepatitis C; direct acting antivirals; breakthrough variants
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MDPI and ACS Style

Ahmed, A.; Felmlee, D.J. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals. Viruses 2015, 7, 6716-6729.

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