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The Role of RASs /RVs in the Current Management of HCV

The approval of combination therapies with direct-acting antiviral (DAA) regimens has led to significant progress in the field of hepatitis C virus (HCV) treatment. Although most patients treated with these agents achieve a virological cure, resistance to DAAs is a major issue. The rapid emergence o...

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Autores principales: Malandris, Konstantinos, Kalopitas, Georgios, Theocharidou, Eleni, Germanidis, Georgios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539246/
https://www.ncbi.nlm.nih.gov/pubmed/34696525
http://dx.doi.org/10.3390/v13102096
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author Malandris, Konstantinos
Kalopitas, Georgios
Theocharidou, Eleni
Germanidis, Georgios
author_facet Malandris, Konstantinos
Kalopitas, Georgios
Theocharidou, Eleni
Germanidis, Georgios
author_sort Malandris, Konstantinos
collection PubMed
description The approval of combination therapies with direct-acting antiviral (DAA) regimens has led to significant progress in the field of hepatitis C virus (HCV) treatment. Although most patients treated with these agents achieve a virological cure, resistance to DAAs is a major issue. The rapid emergence of resistance-associated substitutions (RASs), in particular in the context of incomplete drug pressure, has an impact on sustained virological response (SVR) rates. Several RASs in NS3, NS5A and NS5B have been linked with reduced susceptibility to DAAs. RAS vary based on HCV characteristics and the different drug classes. DAA-resistant HCV variant haplotypes (RVs) are dominant in cases of virological failure. Viruses with resistance to NS3-4A protease inhibitors are only detected in the peripheral blood in a time frame ranging from weeks to months following completion of treatment, whereas NS5A inhibitor-resistant viruses may persist for years. Novel agents have been developed that demonstrate promising results in DAA-experienced patients. The recent approval of broad-spectrum drug combinations with a high genetic barrier to resistance and antiviral potency may overcome the problem of resistance.
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spelling pubmed-85392462021-10-24 The Role of RASs /RVs in the Current Management of HCV Malandris, Konstantinos Kalopitas, Georgios Theocharidou, Eleni Germanidis, Georgios Viruses Review The approval of combination therapies with direct-acting antiviral (DAA) regimens has led to significant progress in the field of hepatitis C virus (HCV) treatment. Although most patients treated with these agents achieve a virological cure, resistance to DAAs is a major issue. The rapid emergence of resistance-associated substitutions (RASs), in particular in the context of incomplete drug pressure, has an impact on sustained virological response (SVR) rates. Several RASs in NS3, NS5A and NS5B have been linked with reduced susceptibility to DAAs. RAS vary based on HCV characteristics and the different drug classes. DAA-resistant HCV variant haplotypes (RVs) are dominant in cases of virological failure. Viruses with resistance to NS3-4A protease inhibitors are only detected in the peripheral blood in a time frame ranging from weeks to months following completion of treatment, whereas NS5A inhibitor-resistant viruses may persist for years. Novel agents have been developed that demonstrate promising results in DAA-experienced patients. The recent approval of broad-spectrum drug combinations with a high genetic barrier to resistance and antiviral potency may overcome the problem of resistance. MDPI 2021-10-18 /pmc/articles/PMC8539246/ /pubmed/34696525 http://dx.doi.org/10.3390/v13102096 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Malandris, Konstantinos
Kalopitas, Georgios
Theocharidou, Eleni
Germanidis, Georgios
The Role of RASs /RVs in the Current Management of HCV
title The Role of RASs /RVs in the Current Management of HCV
title_full The Role of RASs /RVs in the Current Management of HCV
title_fullStr The Role of RASs /RVs in the Current Management of HCV
title_full_unstemmed The Role of RASs /RVs in the Current Management of HCV
title_short The Role of RASs /RVs in the Current Management of HCV
title_sort role of rass /rvs in the current management of hcv
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539246/
https://www.ncbi.nlm.nih.gov/pubmed/34696525
http://dx.doi.org/10.3390/v13102096
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