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

Autor: Shepherd SJ; West of Scotland Specialist Virology Centre, Level 5, New Lister Building, 10-16 Alexandra Parade, Glasgow G31 2ER, United Kingdom. Electronic address: Samantha.Shepherd@ggc.scot.nhs.uk., Abdelrahman T; MRC-University of Glasgow Centre for Virus Research, Stoker Building, 464 Bearsden Road, Glasgow G61 1QH, United Kingdom., MacLean AR; West of Scotland Specialist Virology Centre, Level 5, New Lister Building, 10-16 Alexandra Parade, Glasgow G31 2ER, United Kingdom., Thomson EC; MRC-University of Glasgow Centre for Virus Research, Stoker Building, 464 Bearsden Road, Glasgow G61 1QH, United Kingdom., Aitken C; West of Scotland Specialist Virology Centre, Level 5, New Lister Building, 10-16 Alexandra Parade, Glasgow G31 2ER, United Kingdom., Gunson RN; West of Scotland Specialist Virology Centre, Level 5, New Lister Building, 10-16 Alexandra Parade, Glasgow G31 2ER, United Kingdom.
Jazyk: angličtina
Zdroj: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology [J Clin Virol] 2015 Apr; Vol. 65, pp. 50-3. Date of Electronic Publication: 2015 Feb 09.
DOI: 10.1016/j.jcv.2015.02.005
Abstrakt: 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.
(Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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