{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T18:15:16Z","timestamp":1695492916297},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T00:00:00Z","timestamp":1396483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH 5T32","award":["DK07727-15"],"award-info":[{"award-number":["DK07727-15"]}]},{"name":"NIH NHLBI R34","award":["HL109334"],"award-info":[{"award-number":["HL109334"]}]},{"name":"NIH NIDDK K24","award":["070528"],"award-info":[{"award-number":["070528"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Haemophiliacs have high hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) exposure risk from blood products that did not undergo heat inactivation or disease\u2010specific screening prior to 1987. Repeated exposure to infected factor concentrates predisposes haemophiliacs to higher likelihood of <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> from multiple sources. <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> coinfection could result in impaired clearance of less fit variants resulting in enrichment of quasispecies carrying resistance mutations. We postulated that haemophiliacs demonstrate increased prevalence of baseline signature mutations in the <jats:styled-content style=\"fixed-case\">HCV NS<\/jats:styled-content>3\/4 serine protease coding domain. We examined the prevalence of putative <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> protease inhibitor mutations, mutations, subclassified into dominant mutations if changes conferred resistance, and minor variants not associated with drug resistance, in patients with haemophilia A or B, infected with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>, prior to <jats:styled-content style=\"fixed-case\">HCV PI<\/jats:styled-content> exposure. A total of 151 subjects were evaluated, including 22 haemophiliacs and 129 non\u2010haemophilic controls. Of the 58 mutations detected, 55 (95%) were resistance mutations and three (5%) were minor variants. Dominant mutations were detected in 10 (45.5%) haemophiliacs and in 43 (33.3%) controls (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1.67, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.67\u20134.16). There was no statistical difference in proportion of dominant mutations (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.27) or minor variants (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.47) between groups, despite adjustment for <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> status (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.44). No significant differences in dominant or minor resistance mutations between haemophiliacs and non\u2010haemophiliacs were observed. <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> presence or prior <jats:styled-content style=\"fixed-case\">HAART<\/jats:styled-content> exposure did not affect baseline distribution. We conclude that haemophiliacs are not at higher risk for pre\u2010existing <jats:styled-content style=\"fixed-case\">HCV PI<\/jats:styled-content> mutations, and prospective studies of response to <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\u2010based regimens with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> activity are indicated.<\/jats:p>","DOI":"10.1111\/hae.12420","type":"journal-article","created":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T09:35:14Z","timestamp":1396517714000},"page":"659-665","source":"Crossref","is-referenced-by-count":3,"title":["Hepatitis C virus NS3 mutations in haemophiliacs"],"prefix":"10.1111","volume":"20","author":[{"given":"M. V.","family":"Lin","sequence":"first","affiliation":[{"name":"University of Cincinnati College of Medicine Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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E.","family":"Sherman","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine Cincinnati OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,4,3]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"World Health Organization.http:\/\/www.who.int\/mediacentre\/factsheets\/fs164\/en\/#Accessed October 15 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