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

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

Author information

1
Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
2
Residency program in Microbiology and Virology, Università degli Studi di Milano. Milan, Italy. Electronic address: valeria.cento@unimi.it.
3
Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, BC, Canada.
4
Clinical Microbiology Service, Hospital Universitario San Cecilio, Granada, Spain.
5
Department of Oncology and Oncohematology, Università degli Studi di Milano. Milan, Italy. Electronic address: carlo.perno@unimi.it.
6
Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy. Electronic address: ceccherini@med.uniroma2.it.

Abstract

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

PMID:
29525636
DOI:
10.1016/j.drup.2018.01.004
[Indexed for MEDLINE]

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