The european prevalence of resistance associated substitutions among direct acting antiviral failures
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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; on behalf of the HepCare as Part of the European Society for Translational Antiviral Research (ESAR).
I: Viruses, Bind 14, Nr. 1, 16, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The european prevalence of resistance associated substitutions among direct acting antiviral failures
AU - Popping, Stephanie
AU - Cento, Valeria
AU - Seguin-Devaux, Carole
AU - Boucher, Charles A.B.
AU - de Salazar, Adolfo
AU - Heger, Eva
AU - Mor, Orna
AU - Sayan, Murat
AU - Salmon-Ceron, Dominique
AU - Weis, Nina
AU - Krarup, Henrik B.
AU - de Knegt, Robert J.
AU - Săndulescu, Oana
AU - Chulanov, Vladimir
AU - van de Vijver, David A.M.C.
AU - García, Federico
AU - Ceccherini-Silberstein, Francesca
AU - on behalf of the HepCare as Part of the European Society for Translational Antiviral Research (ESAR)
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Direct-acting antivirals
KW - Elimination
KW - Hepatitis C
KW - Resistance
KW - Resistance associated substitutions
U2 - 10.3390/v14010016
DO - 10.3390/v14010016
M3 - Journal article
C2 - 35062220
AN - SCOPUS:85121665234
VL - 14
JO - Viruses
JF - Viruses
SN - 1999-4915
IS - 1
M1 - 16
ER -
ID: 289156193