Prevalence of HCV NS3 pre-treatment resistance associated amino acid variants within a Scottish cohort

Shepherd, S. J., Abdelrahman, T., MacLean, A. R., Thomson, E. C. , Aitken, C. and Gunson, R. N. (2015) Prevalence of HCV NS3 pre-treatment resistance associated amino acid variants within a Scottish cohort. Journal of Clinical Virology, 65, pp. 50-53. (doi:10.1016/j.jcv.2015.02.005) (PMID:25766988) (PMCID:PMC4728298)

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Abstract

Background: Protease inhibitors (PI) including boceprevir, telaprevir and simeprevir have revolutionised HCV genotype 1 treatment since their introduction. A number of pre-treatment resistance associated amino acid variants (RAVs) and polymorphisms have been associated with reduced response to treatment. Objectives: We measured the prevalence of RAVs/polymorphisms in a PI treatment-naïve HCV genotype 1 Scottish cohort using Sanger sequencing. Study design: Chronically infected, treatment-naïve, HCV genotype 1 patients (n = 146) attending NHS Greater Glasgow and Clyde clinics were investigated for RAVs/polymorphisms to the PIs boceprevir, telaprevir and simeprevir. The NS3/4A region was amplified by nested polymerase chain reaction. The 1.4 kb amplified product was sequenced using an ABI 3710XL DNA sequencer. Sequence analysis was performed using web-based ReCall (beta 2.10). Amino acid positions 36, 41, 43, 54, 55, 80, 109, 122, 155, 156, 168 and 170 were analysed for RAVs/polymorphisms. Results: Overall, 23.29% (34/146) of patients had an RAV or polymorphism detected. Overall, 13.69% (20/146) of patients had HCV virus that contained the Q8 K polymorphism. Other RAVs detected were: V36 M 0.70% (1/146), V36L 0.70% (1/146), T54S 6.85% (10/146), V55A 3.42% (5/146) and V/I170A 0.68% (1/146). Four patients had dual combinations of mutations (T54S + V36L; T54S + V55A and 2 patients with T54S + Q80K). Conclusions: Q80K was the most prevalent baseline polymorphism detected in the Scottish cohort. Simeprevir treatment is not recommended in patients infected with the Q80K genotype 1a variant. This highlights the need for baseline sequencing prior to administration of this drug in this population.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gunson, Dr Rory and Abdelrahman, Dr Tamer and Thomson, Professor Emma and MacLean, Dr Alasdair
Authors: Shepherd, S. J., Abdelrahman, T., MacLean, A. R., Thomson, E. C., Aitken, C., and Gunson, R. N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Clinical Virology
Publisher:Elsevier B.V.
ISSN:1386-6532
ISSN (Online):1873-5967
Copyright Holders:Copyright © 2015 Crown Copyright
First Published:First published in Journal of Clinical Virology 65:50-53
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
645101T-cell mediated evolution of hepatitis C virus during acute infectionEmma ThomsonWellcome Trust (WELLCOME)102789/Z/13/ZMVLS III - CENTRE FOR VIRUS RESEARCH
501441Centre for Integrated VirologyMassimo PalmariniMedical Research Council (MRC)G0801822MVLS III - CENTRE FOR VIRUS RESEARCH
501442Centre for Integrated VirologyMassimo PalmariniMedical Research Council (MRC)G0801822MVLS III - CENTRE FOR VIRUS RESEARCH
501443Centre for Integrated VirologyMassimo PalmariniMedical Research Council (MRC)G0801822MVLS III - CENTRE FOR VIRUS RESEARCH

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