Loading...
Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway
Kjellin, Midori Kileng, Hege Akaberi, Dario Palanisamy, Navaneethan Duberg, Ann-Sofi Danielsson, Astrid Kristiansen, Magnhild Gangsøy Nöjd, Johan Aleman, Soo Gutteberg, Tore
Kjellin, Midori
Kileng, Hege
Akaberi, Dario
Palanisamy, Navaneethan
Duberg, Ann-Sofi
Danielsson, Astrid
Kristiansen, Magnhild Gangsøy
Nöjd, Johan
Aleman, Soo
Gutteberg, Tore
Advisors
Editors
Other Contributors
EPub Date
Publication Date
2019-08-19
Submitted Date
Collections
Files
Loading...
Article - VoR
Adobe PDF, 1.54 MB
Other Titles
Abstract
Background: The NS5A resistance-associated substitution (RAS) Y93H is found quite frequently (5-10%) at baseline in direct-acting antiviral agents (DAA) treatment-naïve genotype (GT) 3a patients when studied by the population-sequencing method (cut-off 20%). This RAS may impair HCV DAA treatment response, since it possesses a high fold in vitro resistance to daclatasvir (DCV) and velpatasvir (VEL) in GT 3. We investigated the effect of baseline Y93H in patients with GT 3a infection on treatment outcome, with or without resistance-based DAA-treatment during 2014-2017. Patients/Methods: Treatment in the intervention group (<i>n</i> = 130) was tailored to baseline resistance-findings by population-sequencing method. Detection of baseline Y93H above 20% prompted a prolonged treatment duration of NS5A-inhibitor and sofosbuvir (SOF) and/or addition of ribavirin (RBV). Patients without baseline Y93H in the intervention group and all patients in the control group (<i>n</i> = 78) received recommended standard DAA-treatment. Results: A higher sustained virologic response rate (SVR) in the intervention group was shown compared to the control group at 95.4% (124/130) and 88.5% (69/78), respectively (<i>p</i> = .06). All five patients with baseline Y93H in the intervention group achieved SVR with personalised treatment based on results from resistance testing; either with the addition of RBV or prolonged treatment duration (24w). In the control group, 2/4 patients with Y93H at baseline treated with ledipasvir/SOF/RBV or DCV/SOF without RBV, failed treatment. Conclusion: The results from this real-life study are in accordance with the findings of the randomised controlled trials in 2015 and the EASL-guidelines of 2016, thus, baseline Y93H impacts on DCV and VEL treatment outcome.
Citation
Kjellin, M., Kileng, H., Akaberi, D., Palanisamy, N., Duberg, A. S., Danielsson, A., ... & Lennerstrand, J. (2019). Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway. Scandinavian journal of gastroenterology, 54(8), 1042-1050. https://doi.org/10.1080/00365521.2019.1652846
Publisher
Taylor & Francis
Journal
Scandinavian Journal of Gastroenterology
Research Unit
DOI
10.1080/00365521.2019.1652846
PubMed ID
PubMed Central ID
Type
Article
Language
en
Description
Series/Report no.
ISSN
0036-5521
EISSN
1502-7708
ISBN
ISMN
Gov't Doc
Test Link
Sponsors
N/A