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dc.contributor.authorAranday-Cortes, E
dc.contributor.authorMcClure, CP
dc.contributor.authorDavis, C
dc.contributor.authorIrving, WL
dc.contributor.authorAdeboyejo, K
dc.contributor.authorTong, L
dc.contributor.authorda Silva Filipe, A
dc.contributor.authorSreenu, V
dc.contributor.authorAgarwal, K
dc.contributor.authorMutimer, D
dc.contributor.authorStone, B
dc.contributor.authorCramp, Matthew
dc.contributor.authorThomson, EC
dc.contributor.authorBall, JK
dc.contributor.authorMcLauchlan, J
dc.date.accessioned2022-03-04T10:22:18Z
dc.date.available2022-03-04T10:22:18Z
dc.date.issued2021-03-01
dc.identifier.issn0022-1899
dc.identifier.issn1537-6613
dc.identifier.urihttp://hdl.handle.net/10026.1/18882
dc.description.abstract

Abstract

Background

Chronic hepatitis C virus (HCV) infection affects 71 million individuals, mostly residing in low- and middle-income countries (LMICs). Direct-acting antivirals (DAAs) give high rates of sustained virological response (SVR) in high-income countries where a restricted range of HCV genotypes/subtypes circulate.

Methods

We studied United Kingdom–resident patients born in Africa to examine DAA effectiveness in LMICs where there is far greater breadth of HCV genotypes/subtypes. Viral genome sequences were determined from 233 patients.

Results

Full-length viral genomic sequences for 26 known subtypes and 5 previously unidentified isolates covering 5 HCV genotypes were determined. From 149 patients who received DAA treatment/retreatment, the overall SVR was 93%. Treatment failure was associated primarily with 2 subtypes, gt1l and gt4r, using sofosbuvir/ledipasvir. These subtypes contain natural resistance-associated variants that likely contribute to poor efficacy with this drug combination. Treatment failure was also significantly associated with hepatocellular carcinoma.

Conclusions

DAA combinations give high SVR rates despite the high HCV diversity across the African continent except for subtypes gt1l and gt4r, which respond poorly to sofosbuvir/ledipasvir. These subtypes are widely distributed across Western, Central, and Eastern Africa. Thus, in circumstances where accurate genotyping is absent, ledipasvir and its generic compounds should not be considered as a recommended treatment option.

dc.format.extent995-1004
dc.format.mediumPrint
dc.languageen
dc.language.isoen
dc.publisherOxford University Press (OUP)
dc.subjectHCV
dc.subjectdirect-acting antiviral
dc.subjectDAA
dc.subjecttreatment outcomes
dc.subjectAfrica
dc.subjectviral genotypes
dc.subjectsubtypes
dc.titleReal-World Outcomes of Direct-Acting Antiviral Treatment and Retreatment in United Kingdom–Based Patients Infected With Hepatitis C Virus Genotypes/Subtypes Endemic in Africa
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000755462800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue6
plymouth.volume226
plymouth.publication-statusPublished
plymouth.journalThe Journal of Infectious Diseases
dc.identifier.doi10.1093/infdis/jiab110
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeUnited States
dcterms.dateAccepted2021-02-23
dc.rights.embargodate2022-3-5
dc.identifier.eissn1537-6613
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1093/infdis/jiab110
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-03-01
rioxxterms.typeJournal Article/Review


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