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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorHowe, Anita
dc.contributor.authorRodrigo, Chaturaka
dc.contributor.authorCunningham, Evan Brian
dc.contributor.authorDouglas, Mark W.
dc.contributor.authorDietz, Julia
dc.contributor.authorGrebely, Jason
dc.contributor.authorQuer Sivila, Josep
dc.date.accessioned2022-08-19T11:14:05Z
dc.date.available2022-08-19T11:14:05Z
dc.date.issued2022-05
dc.identifier.citationHowe AYM, Rodrigo C, Cunningham EB, Douglas MW, Dietz J, Grebely J, et al. Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals. JHEP Rep. 2022 May;4(5):100462.
dc.identifier.issn2589-5559
dc.identifier.urihttp://hdl.handle.net/11351/8024
dc.descriptionVirologic failure; Hepatitis C
dc.description.abstractBackground & Aims Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized.
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofseriesJHEP Reports;4(5)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectMedicaments antivírics
dc.subjectResistència als medicaments
dc.subjectHepatitis C
dc.subject.meshAntiviral Agents
dc.subject.meshDrug Resistance, Viral
dc.subject.meshHepatitis C
dc.titleCharacteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1016/j.jhepr.2022.100462
dc.subject.decsantivíricos
dc.subject.decsfarmacorresistencia viral
dc.subject.decshepatitis C
dc.relation.publishversionhttps://doi.org/10.1016/j.jhepr.2022.100462
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Howe AYM] British Columbia Centre for Disease Control, British Columbia, Canada. [Rodrigo C] School of Medical Sciences, UNSW Sydney, Sydney, Australia. [Cunningham EB, Grebely J] The Kirby Institute, UNSW Sydney, Sydney, Australia. [Douglas MW] Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, Australia. [Dietz J] Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany. [Quer J] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBEREHD, Barcelona, Spain
dc.identifier.pmid35434589
dc.identifier.wos000795853800010
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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