Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1782402996598996992 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4661554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hoffmannluisa nocorrespondencebetweenresistancemutationsinthehcvns3proteaseatbaselineandearlytelaprevirbasedtripletherapy AT faffedeborasouza nocorrespondencebetweenresistancemutationsinthehcvns3proteaseatbaselineandearlytelaprevirbasedtripletherapy AT limajenniferfroescruz nocorrespondencebetweenresistancemutationsinthehcvns3proteaseatbaselineandearlytelaprevirbasedtripletherapy AT capitaniothayannaaraujo nocorrespondencebetweenresistancemutationsinthehcvns3proteaseatbaselineandearlytelaprevirbasedtripletherapy AT cabralbiancacatarinaazeredo nocorrespondencebetweenresistancemutationsinthehcvns3proteaseatbaselineandearlytelaprevirbasedtripletherapy AT urmenyituranpeter nocorrespondencebetweenresistancemutationsinthehcvns3proteaseatbaselineandearlytelaprevirbasedtripletherapy AT coelhohenriquesergiomoraes nocorrespondencebetweenresistancemutationsinthehcvns3proteaseatbaselineandearlytelaprevirbasedtripletherapy AT rondinelliedson nocorrespondencebetweenresistancemutationsinthehcvns3proteaseatbaselineandearlytelaprevirbasedtripletherapy AT villelanogueiracristianealves nocorrespondencebetweenresistancemutationsinthehcvns3proteaseatbaselineandearlytelaprevirbasedtripletherapy AT silvarosane nocorrespondencebetweenresistancemutationsinthehcvns3proteaseatbaselineandearlytelaprevirbasedtripletherapy |