Characterisation of a hepatitis C virus subtype 2a cluster in Scottish PWID with a suboptimal response to glecaprevir/pibrentasvir treatment

Shah, R. et al. (2022) Characterisation of a hepatitis C virus subtype 2a cluster in Scottish PWID with a suboptimal response to glecaprevir/pibrentasvir treatment. Viruses, 14(8), 1678. (doi: 10.3390/v14081678) (PMID:36016300) (PMCID:PMC9416734)

Abstract

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 & 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Shah, Dr Rajiv and Da Silva Filipe, Dr Ana and Gunson, Dr Rory and Shepherd, Dr Samantha and Fox, Dr Raymond and Thomson, Professor Emma and MacLean, Dr Alasdair and Tong, Dr Lily and Davis, Dr Chris and Bradley-Stewart, Dr Amanda
• Authors: Shah, R., Barclay, S. T., Peters, E. S., Fox, R., Gunson, R., Bradley-Stewart, A., Shepherd, S. J., MacLean, A., Tong, L., van Vliet, V. J.E., Bong, M. N. C., Filipe, A., Thomson, E. C., and Davis, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Viruses
• Publisher: MDPI
• ISSN: 1999-4915
• ISSN (Online): 1999-4915
• Published Online: 29 July 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Viruses 14(8): 1678
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172630014		Cross-Cutting Programme – Viral Genomics and Bioinformatics (Programme 9)	David Robertson	Medical Research Council (MRC)	MC_UU_12014/12	III - Centre for Virus Research