RT Journal Article
T1 The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures.
A1 Popping, Stephanie
A1 Cento, Valeria
A1 Seguin-Devaux, Carole
A1 Boucher, Charles A B
A1 de Salazar, Adolfo
A1 Heger, Eva
A1 Mor, Orna
A1 Sayan, Murat
A1 Salmon-Ceron, Dominique
A1 Weis, Nina
A1 Krarup, Henrik B
A1 de Knegt, Robert J
A1 Săndulescu, Oana
A1 Chulanov, Vladimir
A1 van de Vijver, David A M C
A1 García, Federico
A1 Ceccherini-Silberstein, Francesca
K1 direct-acting antivirals
K1 elimination
K1 hepatitis C
K1 resistance
K1 resistance associated substitutions
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.
PB MDPI AG
YR 2021
FD 2021-12-09
LK http://hdl.handle.net/10668/21598
UL http://hdl.handle.net/10668/21598
LA en
NO Popping S, Cento V, Seguin-Devaux C, Boucher CAB, de Salazar A, Heger E, et al.  The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures. Viruses. 2021 Dec 22;14(1):16.
DS RISalud
RD Apr 7, 2025