{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:02:19Z","timestamp":1792839739895,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004423","name":"World Health Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%\u201312% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0\u201392.0) for sofosbuvir\/velpatasvir, 81.0% (95% CI: 67.0\u201393.0) for sofosbuvir\/daclatasvir, and 79.0% (95% CI: 70.0\u201387.0) for glecaprevir\/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0\u201399.0) for sofosbuvir\/velpatasvir\/voxilepravir and in 100% (95% CI: 92.0\u2013100) for glecaprevir\/pibrentasvir, with resistance driven by RAS to NS5A inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciae431","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T15:20:12Z","timestamp":1727709612000},"page":"1437-1446","source":"Crossref","is-referenced-by-count":18,"title":["Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis"],"prefix":"10.1093","volume":"79","author":[{"given":"Seth","family":"Inzaule","sequence":"first","affiliation":[{"name":"Amsterdam Institute for Global Health and Development, and Department of Global Health, Amsterdam UMC, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa","family":"Easterbrook","sequence":"additional","affiliation":[{"name":"HIV, Hepatitis and Sexually Transmitted Infection Department, World Health Organization , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Latona","sequence":"additional","affiliation":[{"name":"Division of Geographic Medicine and Infectious Diseases,Tufts University School of Medicine , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan P","family":"Ford","sequence":"additional","affiliation":[{"name":"HIV, Hepatitis and Sexually Transmitted Infection Department, World Health Organization , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Irving","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Division of Microbiology and Infectious Diseases, The University of Nottingham , Nottingham ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa C","family":"Matthews","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Vitoria","sequence":"additional","affiliation":[{"name":"HIV, Hepatitis and Sexually Transmitted Infection Department, World Health Organization , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Duncombe","sequence":"additional","affiliation":[{"name":"International Association of Providers of AIDS Care , Washington, DC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Giron","sequence":"additional","affiliation":[{"name":"Independent Consultant , Guatemala city, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"McCluskey","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Havard Medical School, Massachusetts General Hospital , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olufunmilayo","family":"Lesi","sequence":"additional","affiliation":[{"name":"HIV, Hepatitis and Sexually Transmitted Infection Department, World Health Organization , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Tchamgoue","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmaceutical Sciences, University of Douala , Douala ,","place":["Cameroon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Halford","sequence":"additional","affiliation":[{"name":"World Hepatitis Alliance , Geneva 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