{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:53:29Z","timestamp":1777452809740,"version":"3.51.4"},"reference-count":23,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The HCV NS3\/4A serine protease inhibitors (PIs) boceprevir (BOC), telaprevir (TVR) and simeprevir (SMV) are approved for treatment of chronic hepatitis C infection in combination with pegylated interferon and ribavirin. The present study investigated the prevalence of HCV NS3 drug resistance mutations (DRMs) associated with HCV genotype-1-infected individuals at baseline and in viral breakthrough following BOC and TVR treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HCV genotype-1-infected individuals were enrolled in a multicentre, prospective outcomes study. The HCV NS3 viral protease was analysed for DRMs at baseline ( n=164) and at viral breakthrough ( n=18) following BOC\/ TVR treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Viral NS3 protease subtype analysis showed 65.2% (107\/164) were HCV subtype-1a and 34.8% (57\/164) were HCV subtype-1b infections. Naturally occurring PI DRMs in NS3 (V36L, T54S, V55A, Q80K\/R and I132V) were identified in 57.3% (94\/164) cases at baseline. The NS3 Q80K polymorphism was found in 43\/107 (40.2%) of HCV subtype-1a and exclusively in clade 1 (43\/82; 52.4%) versus clade 2 viruses (0\/25; 0%, P&lt;10\n                      <jats:sup>-6<\/jats:sup>\n                      ). The pretreatment I132V variant was found in 78.9% (45\/57) of subtype-1b. Of 18 patients who had viral breakthrough, the majority was subtype-1a (77.8%, 14\/18). BOC\/TVR-associated DRMs were detected in 94.4% (17\/18), of which 64.7% (11\/17) emerged on-treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>To ensure the most appropriate direct-acting antiviral-based treatment regimen is employed, baseline reporting of clade and resistance mutations for HCV sub-type-1a using nucleotide sequence-based analysis is warranted prior to commencement of therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp2964","type":"journal-article","created":{"date-parts":[[2015,4,29]],"date-time":"2015-04-29T07:03:30Z","timestamp":1430291010000},"page":"865-869","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Baseline Prevalence and Emergence of Protease Inhibitor Resistance Mutations following Treatment in Chronic HCV Genotype-1-Infected Individuals"],"prefix":"10.1177","volume":"20","author":[{"given":"Linh Thuy","family":"Nguyen","sequence":"first","affiliation":[{"name":"Ireland Vietnam Blood-Borne Virus Initiative (IVVI), Dublin, Ireland and Hanoi, Vietnam"},{"name":"National Virus Reference Laboratory, University College Dublin, Dublin, Ireland"},{"name":"School of Medicine and Medical Science, University College Dublin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Gray","sequence":"additional","affiliation":[{"name":"National Centre for Pharmacoeconomics in Ireland, St James's Hospital, Dublin, Ireland"},{"name":"Irish Hepatitis C Outcomes Research Network (ICORN), Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Dean","sequence":"additional","affiliation":[{"name":"National Virus Reference Laboratory, University College Dublin, Dublin, Ireland"},{"name":"School of Medicine and Medical Science, University College Dublin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Carr","sequence":"additional","affiliation":[{"name":"National Virus Reference Laboratory, University College Dublin, Dublin, Ireland"},{"name":"School of Medicine and Medical Science, University College Dublin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff","family":"Connell","sequence":"additional","affiliation":[{"name":"National Virus Reference Laboratory, University College Dublin, Dublin, Ireland"},{"name":"Irish Hepatitis C Outcomes Research Network (ICORN), Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cillian De","family":"Gascun","sequence":"additional","affiliation":[{"name":"National Virus Reference Laboratory, University College Dublin, Dublin, Ireland"},{"name":"School of Medicine and Medical Science, University College Dublin, Dublin, Ireland"},{"name":"Irish Hepatitis C Outcomes Research Network (ICORN), Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan Anh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Ireland Vietnam Blood-Borne Virus Initiative (IVVI), Dublin, Ireland and Hanoi, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aisling","family":"O'Leary","sequence":"additional","affiliation":[{"name":"National Centre for Pharmacoeconomics in Ireland, St James's Hospital, Dublin, Ireland"},{"name":"Irish Hepatitis C Outcomes Research Network (ICORN), Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colm","family":"Bergin","sequence":"additional","affiliation":[{"name":"Irish Hepatitis C Outcomes Research Network (ICORN), Dublin, Ireland"},{"name":"Department of Genitourinary Medicine and Infectious Diseases, St James's Hospital, Dublin, Ireland"},{"name":"School of Medicine, Trinity College Dublin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Hall","sequence":"additional","affiliation":[{"name":"Ireland Vietnam Blood-Borne Virus Initiative (IVVI), Dublin, Ireland and Hanoi, Vietnam"},{"name":"National Virus Reference Laboratory, University College Dublin, Dublin, Ireland"},{"name":"School of Medicine and Medical Science, University College Dublin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne","family":"Norris","sequence":"additional","affiliation":[{"name":"Irish Hepatitis C Outcomes Research Network (ICORN), Dublin, Ireland"},{"name":"School of Medicine, Trinity College Dublin, Dublin, Ireland"},{"name":"Department of Hepatology, St James's Hospital, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2014,11,1]]},"reference":[{"key":"bibr1-IMP2964","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir774"},{"key":"bibr2-IMP2964","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-014-0413-1"},{"key":"bibr3-IMP2964","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2014.02.011"},{"key":"bibr4-IMP2964","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr581"},{"key":"bibr5-IMP2964","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-9-245"},{"key":"bibr6-IMP2964","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328363b1f9"},{"key":"bibr7-IMP2964","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.04.018"},{"key":"bibr8-IMP2964","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/273856"},{"key":"bibr9-IMP2964","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086413"},{"key":"bibr10-IMP2964","doi-asserted-by":"publisher","DOI":"10.7448\/IAS.17.4.19741"},{"key":"bibr11-IMP2964","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.11.003"},{"key":"bibr12-IMP2964","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01976-13"},{"key":"bibr13-IMP2964","doi-asserted-by":"crossref","first-page":"743A","DOI":"10.1016\/j.jhep.2012.11.038","volume":"58","author":"Lenz 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