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Hepatitis C subtyping assay failure in UK patients born in sub-Saharan Africa: Implications for global treatment and elimination

Adeboyejo, Kazeem; King, Barnabas; Tsoleridis, Theocharis; Tarr, Alexander W.; McLauchlan, John; Irving, William L.; Ball, Jonathan K.; McClure, C. Patrick

Hepatitis C subtyping assay failure in UK patients born in sub-Saharan Africa: Implications for global treatment and elimination Thumbnail


Authors

Kazeem Adeboyejo

Barnabas King

Theocharis Tsoleridis

John McLauchlan

JONATHAN BALL jonathan.ball@nottingham.ac.uk
Professor of Molecular Virology



Abstract

Background andAims: The newly developed direct-acting antivirals have revolutionized the treatment of chronic hepatitis C virus (HCV), with cure rates as high as 98% in some cohorts. Although genome sequencing has demonstrated that some subtypes of HCV naturally harbor drug resistance associated substitutions (RAS), these are often overlooked as “rarities.” Furthermore, commercial subtyping assays and associated epidemiological findings are skewed towards Western cohorts and whole-genome sequencing can be problematic to deploy without significant infrastructure and training support. We thus aimed to develop a simple, robust and accurate HCV subtyping pipeline, to optimize and streamline molecular detection and sequence-based typing of diverse RAS-containing subtypes. Methods: HCV serum derived from 146 individuals, whose likely source of infection was from sub-Saharan Africa (SSA) was investigated with a novel panel of single round polymerase chain reaction(PCR) assays targeting NS5B and NS5A genomic regions. Virus subtype assignments were determined by pairwise-distance analysis and compared to both diagnostic laboratory assignments and free-to-use online typing tools. Results: Partial NS5A and NS5B sequences were respectively obtained from 131 to 135 HCV-positive patients born in 19 different countries from SSA but attending clinics in the UK. We determined that routine clinical diagnostic methods incorrectly subtyped 59.0% of samples, with a further 6.8% incorrectly genotyped. Of five commonly used online tools, Geno2Pheno performed most effectively in determining a subtype in agreement with pairwise distance analysis. Conclusion: This study provides a simple low-cost pathway to accurately subtype in SSA, guide regional therapeutic choice and assist global surveillance and elimination initiatives.

Journal Article Type Article
Acceptance Date Sep 26, 2022
Online Publication Date Sep 27, 2022
Publication Date Jan 1, 2023
Deposit Date Oct 1, 2022
Publicly Available Date Nov 11, 2022
Journal Journal of Medical Virology
Print ISSN 0146-6615
Electronic ISSN 1096-9071
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 95
Issue 1
Article Number e28178
DOI https://doi.org/10.1002/jmv.28178
Keywords Infectious Diseases; Virology
Public URL https://nottingham-repository.worktribe.com/output/11756134
Publisher URL https://onlinelibrary.wiley.com/doi/10.1002/jmv.28178