{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:15:45Z","timestamp":1762866945732},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,9,25]],"date-time":"2016-09-25T00:00:00Z","timestamp":1474761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001773","name":"University of New South Wales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001773","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2017,1]]},"abstract":"Summary<\/jats:title>Several direct\u2010acting antivirals (DAA<\/jats:styled-content>s) have been approved for the treatment of chronic hepatitis C virus (HCV<\/jats:styled-content>) infections, opening the door to highly effective interferon\u2010free treatment regimens. Resistance\u2010associated substitutions (RAS<\/jats:styled-content>s) have been reported both in treatment\u2010na\u00efve patients and following treatment with protease (NS<\/jats:styled-content>3), phosphoprotein (NS<\/jats:styled-content>5A) and polymerase (NS<\/jats:styled-content>5B) inhibitors. The prevalence of naturally occurring RAS<\/jats:styled-content>s in untreated HCV<\/jats:styled-content>\u2010infected individuals has mostly been analysed in those infected with genotype 1 (GT<\/jats:styled-content>1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RAS<\/jats:styled-content>s remains poorly characterized. In this study, we used next\u2010generation sequencing to analyse full\u2010length HCV<\/jats:styled-content> genomes for the prevalence of RAS<\/jats:styled-content>s in acute HCV<\/jats:styled-content> infections identified in nine international prospective cohorts. RAS<\/jats:styled-content>s were analysed in 179 participants infected with all six major HCV<\/jats:styled-content> genotypes (GT<\/jats:styled-content>1\u2010GT<\/jats:styled-content>6), and the geographic distribution of RAS<\/jats:styled-content>s was assessed in 107 GT<\/jats:styled-content>1a and GT<\/jats:styled-content>3a samples. While RAS<\/jats:styled-content>s were detected at varied frequencies across the three genomic regions, and between genotypes, RAS<\/jats:styled-content>s relevant to multiple DAA<\/jats:styled-content>s in the leading IFN<\/jats:styled-content>\u2010free regimens were rarely detected in combination. Low\u2010frequency RAS<\/jats:styled-content>s (<10% of the viral population) were also shown to have a GT<\/jats:styled-content>\u2010specific distribution. The main RAS<\/jats:styled-content>s with geographic associations were NS<\/jats:styled-content>3 Q80K in GT<\/jats:styled-content>1a samples and NS<\/jats:styled-content>5B N142T in GT<\/jats:styled-content>3a. These data provide the backdrop for prospective surveillance of RAS<\/jats:styled-content>s during DAA<\/jats:styled-content> treatment scale\u2010up.<\/jats:p>","DOI":"10.1111\/jvh.12615","type":"journal-article","created":{"date-parts":[[2016,9,25]],"date-time":"2016-09-25T23:06:39Z","timestamp":1474844799000},"page":"37-42","source":"Crossref","is-referenced-by-count":11,"title":["Analysis of resistance\u2010associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents"],"prefix":"10.1111","volume":"24","author":[{"given":"A. A.","family":"Eltahla","sequence":"first","affiliation":[{"name":"School of Medical Sciences Faculty of Medicine UNSW Australia Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Rodrigo","sequence":"additional","affiliation":[{"name":"School of Medical Sciences Faculty of Medicine UNSW Australia Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Betz\u2010Stablein","sequence":"additional","affiliation":[{"name":"School of Medical Sciences Faculty of Medicine UNSW Australia Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Grebely","sequence":"additional","affiliation":[{"name":"The Kirby Institute UNSW Australia Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Applegate","sequence":"additional","affiliation":[{"name":"The Kirby Institute UNSW Australia Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Luciani","sequence":"additional","affiliation":[{"name":"School of Medical Sciences Faculty of Medicine UNSW Australia Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Schinkel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Infectious Diseases Tropical Medicine and AIDS Center for Infection and Immunity Amsterdam Academic Medical Center Meibergdreef Amsterdam The Netherlands"},{"name":"GGD Public Health Service of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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L.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Medicine Johns Hopkins Medical Institutions Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Y.","family":"Kim","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. H.","family":"Shoukry","sequence":"additional","affiliation":[{"name":"CRCHUM Universit\u00e9 de Montr\u00e9al Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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