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Clinical impact of the hepatitis C virus mutations in the era of directly acting antivirals
Author(s) -
Coppola Nicola,
Minichini Carmine,
Starace Mario,
Sagnelli Caterina,
Sagnelli Evangelista
Publication year - 2016
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.24527
Subject(s) - ns5a , virology , ns3 , ns5b , hepatitis c virus , tolerability , discontinuation , medicine , virus , hepacivirus , biology , pharmacology , adverse effect
Introduced in 2013–2014, the second‐ and third‐wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti‐HCV treatment, with a sustained virological response (SVR) in 90–95% of cases treated. The majority of patients who did not achieve an SVR were found to be infected with HCV strains with a reduced susceptibility to these drugs. Indeed, the high error rate of the viral polymerase and a fast virion production (100‐fold higher than the human immunodeficiency virus) result in a mixture of viral genetic populations (quasi‐species) pre‐existing treatment initiation. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A region and rarely in the NS5B region. Treatment‐induced resistant mutants to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration. This review focuses on the type and prevalence of viral strains with a reduced sensitivity to DAAs, their clinical impact and influence on the response to treatment and, consequently, on treatment choice for DAA‐experienced patients. J. Med. Virol. 88:1659–1671, 2016 . © 2016 Wiley Periodicals, Inc.