Universität zu Köln

Popping, Stephanie, Cento, Valeria ORCID: 0000-0002-3272-4252, Seguin-Devaux, Carole ORCID: 0000-0003-0636-5222, Boucher, Charles A. B., de Salazar, Adolfo, Heger, Eva, Mor, Orna ORCID: 0000-0003-3207-4226, Sayan, Murat ORCID: 0000-0002-4374-7193, Salmon-Ceron, Dominique, Weis, Nina, Krarup, Henrik B., de Knegt, Robert J., Sandulescu, Oana ORCID: 0000-0002-2586-4070, Chulanov, Vladimir ORCID: 0000-0001-6303-9293, van de Vijver, David A. M. C., Garcia, Federico ORCID: 0000-0001-7611-781X and Ceccherini-Silberstein, Francesca (2022). The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures. Viruses-Basel, 14 (1). BASEL: MDPI. ISSN 1999-4915

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Popping, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Cento, Valeria UNSPECIFIED orcid.org/0000-0002-3272-4252 UNSPECIFIED Seguin-Devaux, Carole UNSPECIFIED orcid.org/0000-0003-0636-5222 UNSPECIFIED Boucher, Charles A. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Salazar, Adolfo UNSPECIFIED UNSPECIFIED UNSPECIFIED Heger, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Mor, Orna UNSPECIFIED orcid.org/0000-0003-3207-4226 UNSPECIFIED Sayan, Murat UNSPECIFIED orcid.org/0000-0002-4374-7193 UNSPECIFIED Salmon-Ceron, Dominique UNSPECIFIED UNSPECIFIED UNSPECIFIED Weis, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Krarup, Henrik B. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Knegt, Robert J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sandulescu, Oana UNSPECIFIED orcid.org/0000-0002-2586-4070 UNSPECIFIED Chulanov, Vladimir UNSPECIFIED orcid.org/0000-0001-6303-9293 UNSPECIFIED van de Vijver, David A. M. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia, Federico UNSPECIFIED orcid.org/0000-0001-7611-781X UNSPECIFIED Ceccherini-Silberstein, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-697386
DOI:	10.3390/v14010016
Journal or Publication Title:	Viruses-Basel
Volume:	14
Number:	1
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1999-4915
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEPATITIS-C VIRUS; HCV INFECTION; GENOTYPE 1; REAL-LIFE; SOFOSBUVIR; VELPATASVIR; VOXILAPREVIR; THERAPY; NS5A Multiple languages Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69738