Real-world outcomes of DAA treatment and retreatment in UK-based patients infected with HCV genotypes/subtypes endemic in Africa

Aranday-Cortes, E. et al. (2021) Real-world outcomes of DAA treatment and retreatment in UK-based patients infected with HCV genotypes/subtypes endemic in Africa. Journal of Infectious Diseases, (doi: 10.1093/infdis/jiab110) (In Press)

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Abstract

Background: Chronic HCV infection affects 71 million individuals, mostly residing in low- and middle-income countries (LMICs). Direct-acting antivirals (DAA) give high rates of sustained virological response (SVR) in high income countries where a restricted range of HCV genotypes/subtypes circulate. Approach: We studied UK-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 two 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.

Item Type:Articles
Additional Information:This work was funded by the UK Medical Research Council (MC_UU_12014/1). HCV Research UK received support from the Medical Research Foundation (C0365). ECT was also funded by the Wellcome Trust (102789/Z/13/A). KA (Adeboyejo) was supported by the Tertiary Education Trust Fund (TETFUND) and the NIHR Nottingham Biomedical Research Centre.
Status:In Press
Refereed:Yes
Glasgow Author(s) Enlighten ID:Thomson, Professor Emma and Tong, Dr Lily and Vattipally, Dr Sreenu and Da Silva Filipe, Dr Ana and McLauchlan, Professor John
Authors: Aranday-Cortes, E., McClure, C. P., Davis, C., Irving, W. L., Adeboyejo, K., Tong, L., Da Silva Filipe, A., Sreenu, V., Agarwal, K., Mutimer, D., Stone, B., Cramp, M. E., Thomson, E. C., Ball, J. K., and McLauchlan, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Infectious Diseases
Publisher:Oxford University Press
ISSN:0022-1899
ISSN (Online):1537-6613
Published Online:01 March 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Journal of Infectious Diseases 2021
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
Medical Research Council (MRC)MC_UU_12014/1
169538T-cell mediated evolution of hepatitis C virus during acute infectionEmma ThomsonWellcome Trust (WELLCOTR)102789/Z/13/ZIII-MRC-GU Centre for Virus Research