{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:01:42Z","timestamp":1792839702353,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MRC","award":["MC UU1201412"],"award-info":[{"award-number":["MC UU1201412"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Direct-acting antivirals (DAAs) have revolutionised the treatment of Hepatitis C virus (HCV), allowing the World Health Organisation (WHO) to set a target of eliminating HCV by 2030. In this study we aimed to investigate glecaprevir and pibrentasvir (GP) treatment outcomes in a cohort of patients with genotype 2a infection. Methods: Clinical data and plasma samples were collected in NHS Greater Glasgow &amp; Clyde. Next generation whole genome sequencing and replicon assays were carried out at the MRC-University of Glasgow Centre for Virus Research. Results: 132 cases infected with genotype 2a HCV were identified. The SVR rate for this group was 91% (112\/123) following treatment with GP. An NS5A polymorphism, L31M, was detected in all cases of g2a infection, and L31M+R353K in individuals that failed treatment. The results showed that R353K was present in 90% of individuals in the Glasgow genotype 2a phylogenetic cluster but in less than 5% of all HCV subtype 2a published sequences. In vitro efficacy of pibrentasvir against sub-genomic replicon constructs containing these mutations showed a 2-fold increase in IC50 compared to wildtype. Conclusion: This study describes a cluster of HCV genotype 2a infection associated with a lower-than-expected SVR rate following GP treatment in association with the NS5A mutations L31M+R353K.<\/jats:p>","DOI":"10.3390\/v14081678","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T23:49:27Z","timestamp":1659397767000},"page":"1678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir\/Pibrentasvir Treatment"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2827-5108","authenticated-orcid":false,"given":"Rajiv","family":"Shah","sequence":"first","affiliation":[{"name":"Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0415-785X","authenticated-orcid":false,"given":"Stephen T.","family":"Barclay","sequence":"additional","affiliation":[{"name":"NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica S.","family":"Peters","sequence":"additional","affiliation":[{"name":"NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"Fox","sequence":"additional","affiliation":[{"name":"NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Gunson","sequence":"additional","affiliation":[{"name":"Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"},{"name":"NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Bradley-Stewart","sequence":"additional","affiliation":[{"name":"NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"Shepherd","sequence":"additional","affiliation":[{"name":"NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alasdair","family":"MacLean","sequence":"additional","affiliation":[{"name":"NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Tong","sequence":"additional","affiliation":[{"name":"Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera Jannie Elisabeth","family":"van Vliet","sequence":"additional","affiliation":[{"name":"Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0807-2212","authenticated-orcid":false,"given":"Michael","family":"Ngan Chiu Bong","sequence":"additional","affiliation":[{"name":"Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Filipe","sequence":"additional","affiliation":[{"name":"Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1482-0889","authenticated-orcid":false,"given":"Emma C.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"},{"name":"NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Davis","sequence":"additional","affiliation":[{"name":"Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus 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