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Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data

Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) proteins open a whole new era for anti-HCV therapy, but DAA resistance associated variants (RAVs) could jeopardize the effectiveness of DAAs. We reported the global prevalence of DAA RAVs using published GenBank data. 58.7% of seq...

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Autores principales: Chen, Zhi-wei, Li, Hu, Ren, Hong, Hu, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740856/
https://www.ncbi.nlm.nih.gov/pubmed/26842909
http://dx.doi.org/10.1038/srep20310
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author Chen, Zhi-wei
Li, Hu
Ren, Hong
Hu, Peng
author_facet Chen, Zhi-wei
Li, Hu
Ren, Hong
Hu, Peng
author_sort Chen, Zhi-wei
collection PubMed
description Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) proteins open a whole new era for anti-HCV therapy, but DAA resistance associated variants (RAVs) could jeopardize the effectiveness of DAAs. We reported the global prevalence of DAA RAVs using published GenBank data. 58.7% of sequences (854/1455) harbored at least one dominant resistance variant and the highest RAV frequency occurred in Asia (74.1%), followed by Africa (71.9%), America (53.5%) and Europe (51.4%). The highest RAV frequency was observed in genotype (GT) 6 sequences (99%), followed by GT2 (87.9%), GT4 (85.5%), GT1a (56%), GT3 (50.0%) and GT1b (34.3%). Furthermore, 40.0% and 29.6% of sequences were detected RAVs of non-structural (NS) 5A inhibitors and NS3 protease inhibitors, respectively. However, RAVs to NS5B nucleo(t)ide inhibitor (NI) and NI-based combinations were uncommon (<4% of sequences). As expected, combinations of multiple RAVs to the IFN-free regimens recommended by current guidelines were rarely detected (0.2%–2.0%). Our results showed that the overall global prevalence of DAA RAVs was high irrespective of geography or genotype. However, the NI-based multi-DAA regimens had a low RAV prevalence, suggesting that these regimens are the most promising strategies for cure of the long-term HCV infection.
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spelling pubmed-47408562016-02-09 Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data Chen, Zhi-wei Li, Hu Ren, Hong Hu, Peng Sci Rep Article Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) proteins open a whole new era for anti-HCV therapy, but DAA resistance associated variants (RAVs) could jeopardize the effectiveness of DAAs. We reported the global prevalence of DAA RAVs using published GenBank data. 58.7% of sequences (854/1455) harbored at least one dominant resistance variant and the highest RAV frequency occurred in Asia (74.1%), followed by Africa (71.9%), America (53.5%) and Europe (51.4%). The highest RAV frequency was observed in genotype (GT) 6 sequences (99%), followed by GT2 (87.9%), GT4 (85.5%), GT1a (56%), GT3 (50.0%) and GT1b (34.3%). Furthermore, 40.0% and 29.6% of sequences were detected RAVs of non-structural (NS) 5A inhibitors and NS3 protease inhibitors, respectively. However, RAVs to NS5B nucleo(t)ide inhibitor (NI) and NI-based combinations were uncommon (<4% of sequences). As expected, combinations of multiple RAVs to the IFN-free regimens recommended by current guidelines were rarely detected (0.2%–2.0%). Our results showed that the overall global prevalence of DAA RAVs was high irrespective of geography or genotype. However, the NI-based multi-DAA regimens had a low RAV prevalence, suggesting that these regimens are the most promising strategies for cure of the long-term HCV infection. Nature Publishing Group 2016-02-04 /pmc/articles/PMC4740856/ /pubmed/26842909 http://dx.doi.org/10.1038/srep20310 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chen, Zhi-wei
Li, Hu
Ren, Hong
Hu, Peng
Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data
title Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data
title_full Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data
title_fullStr Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data
title_full_unstemmed Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data
title_short Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data
title_sort global prevalence of pre-existing hcv variants resistant to direct-acting antiviral agents (daas): mining the genbank hcv genome data
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740856/
https://www.ncbi.nlm.nih.gov/pubmed/26842909
http://dx.doi.org/10.1038/srep20310
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