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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
UiT Arctic Univ Norway, Dept Clin Med, Gastroenterol & Nutr Res Grp, Tromso, Norway;Univ Hosp North Norway, Dept Med, Tromso, Norway.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
Heidelberg Univ, HBIGS, Heidelberg, Germany;Univ Freiburg, Inst Biol 2, Freiburg, Germany.
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2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 8, p. 1042-1050Article in journal (Refereed) Published
Abstract [en]

Background: The NS5A resistance-associated substitution (RAS) Y93H is found quite frequently (5-10%) at baseline in direct-acting antiviral agents (DAA) treatment-naive 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 (n = 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 (n = 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 (p = .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.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD , 2019. Vol. 54, no 8, p. 1042-1050
Keywords [en]
Baseline resistance, hepatitis C virus, NS5A, resistance-associated substitution, sustained virologic response, Y93H
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:uu:diva-396109DOI: 10.1080/00365521.2019.1652846ISI: 000481902500001PubMedID: 31424972OAI: oai:DiVA.org:uu-396109DiVA, id: diva2:1367128
Funder
Erik, Karin och Gösta Selanders FoundationAvailable from: 2019-11-01 Created: 2019-11-01 Last updated: 2019-11-01Bibliographically approved

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