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No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy

Direct-acting antiviral (DAA)-based therapy is the new standard treatment for chronic hepatitis C virus (HCV) infection. However, protease inhibitor (PI)-resistant viral variants have been often described. This study aimed to examine HCV-NS3 protease variants at baseline and at 4 weeks under triple...

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Autores principales: Hoffmann, Luísa, Faffe, Débora Souza, Lima, Jennifer Fróes Cruz, Capitanio, Thayanna Araujo, Cabral, Bianca Catarina Azeredo, Ürményi, Turán Péter, Coelho, Henrique Sergio Moraes, Rondinelli, Edson, Villela-Nogueira, Cristiane Alves, Silva, Rosane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661554/
https://www.ncbi.nlm.nih.gov/pubmed/26674563
http://dx.doi.org/10.1016/j.bbacli.2015.01.004
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author Hoffmann, Luísa
Faffe, Débora Souza
Lima, Jennifer Fróes Cruz
Capitanio, Thayanna Araujo
Cabral, Bianca Catarina Azeredo
Ürményi, Turán Péter
Coelho, Henrique Sergio Moraes
Rondinelli, Edson
Villela-Nogueira, Cristiane Alves
Silva, Rosane
author_facet Hoffmann, Luísa
Faffe, Débora Souza
Lima, Jennifer Fróes Cruz
Capitanio, Thayanna Araujo
Cabral, Bianca Catarina Azeredo
Ürményi, Turán Péter
Coelho, Henrique Sergio Moraes
Rondinelli, Edson
Villela-Nogueira, Cristiane Alves
Silva, Rosane
author_sort Hoffmann, Luísa
collection PubMed
description Direct-acting antiviral (DAA)-based therapy is the new standard treatment for chronic hepatitis C virus (HCV) infection. However, protease inhibitor (PI)-resistant viral variants have been often described. This study aimed to examine HCV-NS3 protease variants at baseline and at 4 weeks under triple therapy. To this end, we analyzed the presence of variants in HCV-NS3 protease region from peripheral blood samples of 16 patients infected with HCV-1 at baseline and at 4 weeks of combined therapy with telaprevir, pegylated interferon, and ribavirin, using next-generation sequencing. Several variants with synonymous and non-synonymous amino acid substitutions were detected at both time points. Variants detected at low frequency corresponded to 74% (HCV-1a) and 35% (HCV-1b) of non-synonymous substitutions. We found nine PI-resistance-associated variants (V36A, T54S, V55I, Q80K, Q80R, V107I, I132V, D168E, M175L) in HCV-NS3 of 10 patients. There was no correspondence of resistance-associated variant profile between baseline and at 4 weeks. Moreover, these resistance variants at baseline and short-term treatment are not good predictors of outcome under triple therapy. Our study also shows a large number of others minor and major non-synonymous variants in HCV-NS3 early in telaprevir-based therapy that can be important for further drug resistance association studies with newly developed PI agents.
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spelling pubmed-46615542015-12-15 No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy Hoffmann, Luísa Faffe, Débora Souza Lima, Jennifer Fróes Cruz Capitanio, Thayanna Araujo Cabral, Bianca Catarina Azeredo Ürményi, Turán Péter Coelho, Henrique Sergio Moraes Rondinelli, Edson Villela-Nogueira, Cristiane Alves Silva, Rosane BBA Clin Regular Article Direct-acting antiviral (DAA)-based therapy is the new standard treatment for chronic hepatitis C virus (HCV) infection. However, protease inhibitor (PI)-resistant viral variants have been often described. This study aimed to examine HCV-NS3 protease variants at baseline and at 4 weeks under triple therapy. To this end, we analyzed the presence of variants in HCV-NS3 protease region from peripheral blood samples of 16 patients infected with HCV-1 at baseline and at 4 weeks of combined therapy with telaprevir, pegylated interferon, and ribavirin, using next-generation sequencing. Several variants with synonymous and non-synonymous amino acid substitutions were detected at both time points. Variants detected at low frequency corresponded to 74% (HCV-1a) and 35% (HCV-1b) of non-synonymous substitutions. We found nine PI-resistance-associated variants (V36A, T54S, V55I, Q80K, Q80R, V107I, I132V, D168E, M175L) in HCV-NS3 of 10 patients. There was no correspondence of resistance-associated variant profile between baseline and at 4 weeks. Moreover, these resistance variants at baseline and short-term treatment are not good predictors of outcome under triple therapy. Our study also shows a large number of others minor and major non-synonymous variants in HCV-NS3 early in telaprevir-based therapy that can be important for further drug resistance association studies with newly developed PI agents. Elsevier 2015-01-30 /pmc/articles/PMC4661554/ /pubmed/26674563 http://dx.doi.org/10.1016/j.bbacli.2015.01.004 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Regular Article
Hoffmann, Luísa
Faffe, Débora Souza
Lima, Jennifer Fróes Cruz
Capitanio, Thayanna Araujo
Cabral, Bianca Catarina Azeredo
Ürményi, Turán Péter
Coelho, Henrique Sergio Moraes
Rondinelli, Edson
Villela-Nogueira, Cristiane Alves
Silva, Rosane
No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy
title No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy
title_full No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy
title_fullStr No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy
title_full_unstemmed No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy
title_short No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy
title_sort no correspondence between resistance mutations in the hcv-ns3 protease at baseline and early telaprevir-based triple therapy
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661554/
https://www.ncbi.nlm.nih.gov/pubmed/26674563
http://dx.doi.org/10.1016/j.bbacli.2015.01.004
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