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The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures

Background: Approximately 71 million people are still in need of direct-acting antiviral agents (DAAs). To achieve the World Health Organization Hepatitis C elimination goals, insight into the prevalence and influence of resistance associated substitutions (RAS) is of importance. Collaboration is ke...

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Autores principales: Popping, Stephanie, Cento, Valeria, Seguin-Devaux, Carole, Boucher, Charles A. B., de Salazar, Adolfo, Heger, Eva, Mor, Orna, Sayan, Murat, Salmon-Ceron, Dominique, Weis, Nina, Krarup, Henrik B., de Knegt, Robert J., Săndulescu, Oana, Chulanov, Vladimir, van de Vijver, David A. M. C., García, Federico, Ceccherini-Silberstein, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781716/
https://www.ncbi.nlm.nih.gov/pubmed/35062220
http://dx.doi.org/10.3390/v14010016
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author Popping, Stephanie
Cento, Valeria
Seguin-Devaux, Carole
Boucher, Charles A. B.
de Salazar, Adolfo
Heger, Eva
Mor, Orna
Sayan, Murat
Salmon-Ceron, Dominique
Weis, Nina
Krarup, Henrik B.
de Knegt, Robert J.
Săndulescu, Oana
Chulanov, Vladimir
van de Vijver, David A. M. C.
García, Federico
Ceccherini-Silberstein, Francesca
author_facet Popping, Stephanie
Cento, Valeria
Seguin-Devaux, Carole
Boucher, Charles A. B.
de Salazar, Adolfo
Heger, Eva
Mor, Orna
Sayan, Murat
Salmon-Ceron, Dominique
Weis, Nina
Krarup, Henrik B.
de Knegt, Robert J.
Săndulescu, Oana
Chulanov, Vladimir
van de Vijver, David A. M. C.
García, Federico
Ceccherini-Silberstein, Francesca
author_sort Popping, Stephanie
collection PubMed
description Background: Approximately 71 million people are still in need of direct-acting antiviral agents (DAAs). To achieve the World Health Organization Hepatitis C elimination goals, insight into the prevalence and influence of resistance associated substitutions (RAS) is of importance. Collaboration is key since DAA failure is rare and real-life data are scattered. We have established a European collaboration, HepCare, to perform in-depth analysis regarding RAS prevalence, patterns, and multiclass occurrence. Methods: Data were extracted from the HepCare cohort of patients who previously failed DAA therapy. Geno—and subtypes were provided by submitters and mostly based on in-house assays. They were reassessed using the Comet HCV subtyping tool. We considered RAS to be relevant if they were associated with DAA failure in vivo previously reported in literature. Results: We analyzed 938 patients who failed DAA therapy from ten different European countries. There were 239 genotypes (GT) 1a, 380 GT1b, 19 GT2c, 205 GT3a, 14 GT4a, and 68 GT4d infections. Several unusual subtypes (n = 15) (GT1b/g/l, GT3b, GT4k/n/r/t) were present. RAS appeared in over 80% of failures and over a quarter had three or more RAS. Multiclass RAS varied over target region and genotype between 0–48%. RAS patterns such as the Q30R + L31M and Q30R + Y93H in GT1a, the L31V + Y93H and L31V + Y93H for GT1b, and A30K + L31M and A30K/V + Y93H for GT3a all occurred with a prevalence below 5%. Conclusion: RAS occur frequently after DAA failures and follow a specific genotype and drug related pattern. Interpretation of the influence of RAS on retreatment is challenging due to various patterns, patients’ characteristics, and previous treatment history. Moving towards HCV elimination, an ongoing resistance surveillance is essential to track the presence of RAS, RAS patterns and gather data for a re-treatment algorithm.
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spelling pubmed-87817162022-01-22 The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures Popping, Stephanie Cento, Valeria Seguin-Devaux, Carole Boucher, Charles A. B. de Salazar, Adolfo Heger, Eva Mor, Orna Sayan, Murat Salmon-Ceron, Dominique Weis, Nina Krarup, Henrik B. de Knegt, Robert J. Săndulescu, Oana Chulanov, Vladimir van de Vijver, David A. M. C. García, Federico Ceccherini-Silberstein, Francesca Viruses Article Background: Approximately 71 million people are still in need of direct-acting antiviral agents (DAAs). To achieve the World Health Organization Hepatitis C elimination goals, insight into the prevalence and influence of resistance associated substitutions (RAS) is of importance. Collaboration is key since DAA failure is rare and real-life data are scattered. We have established a European collaboration, HepCare, to perform in-depth analysis regarding RAS prevalence, patterns, and multiclass occurrence. Methods: Data were extracted from the HepCare cohort of patients who previously failed DAA therapy. Geno—and subtypes were provided by submitters and mostly based on in-house assays. They were reassessed using the Comet HCV subtyping tool. We considered RAS to be relevant if they were associated with DAA failure in vivo previously reported in literature. Results: We analyzed 938 patients who failed DAA therapy from ten different European countries. There were 239 genotypes (GT) 1a, 380 GT1b, 19 GT2c, 205 GT3a, 14 GT4a, and 68 GT4d infections. Several unusual subtypes (n = 15) (GT1b/g/l, GT3b, GT4k/n/r/t) were present. RAS appeared in over 80% of failures and over a quarter had three or more RAS. Multiclass RAS varied over target region and genotype between 0–48%. RAS patterns such as the Q30R + L31M and Q30R + Y93H in GT1a, the L31V + Y93H and L31V + Y93H for GT1b, and A30K + L31M and A30K/V + Y93H for GT3a all occurred with a prevalence below 5%. Conclusion: RAS occur frequently after DAA failures and follow a specific genotype and drug related pattern. Interpretation of the influence of RAS on retreatment is challenging due to various patterns, patients’ characteristics, and previous treatment history. Moving towards HCV elimination, an ongoing resistance surveillance is essential to track the presence of RAS, RAS patterns and gather data for a re-treatment algorithm. MDPI 2021-12-22 /pmc/articles/PMC8781716/ /pubmed/35062220 http://dx.doi.org/10.3390/v14010016 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 Article
Popping, Stephanie
Cento, Valeria
Seguin-Devaux, Carole
Boucher, Charles A. B.
de Salazar, Adolfo
Heger, Eva
Mor, Orna
Sayan, Murat
Salmon-Ceron, Dominique
Weis, Nina
Krarup, Henrik B.
de Knegt, Robert J.
Săndulescu, Oana
Chulanov, Vladimir
van de Vijver, David A. M. C.
García, Federico
Ceccherini-Silberstein, Francesca
The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures
title The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures
title_full The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures
title_fullStr The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures
title_full_unstemmed The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures
title_short The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures
title_sort european prevalence of resistance associated substitutions among direct acting antiviral failures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781716/
https://www.ncbi.nlm.nih.gov/pubmed/35062220
http://dx.doi.org/10.3390/v14010016
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