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

Autor: Rasmus Goll, Hege Kileng, Anders Lannergård, Soo Aleman, Magnhild Gangsøy Kristiansen, Navaneethan Palanisamy, Midori Kjellin, Johan Lennerstrand, Astrid Danielsson, Dario Akaberi, Johan Edvin Nöjd, Tore Jarl Gutteberg, Ann-Sofi Duberg
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Adult
Male
Oncology
hepatitis C virus
medicine.medical_specialty
Genotype
Sustained Virologic Response
Hepatitis C virus
Y93H
Hepacivirus
Gastroenterology and Hepatology
Viral Nonstructural Proteins
medicine.disease_cause
NS5A
Antiviral Agents
Young Adult
03 medical and health sciences
0302 clinical medicine
Internal medicine
Drug Resistance
Viral
medicine
Gastroenterologi
Humans
VDP::Medisinske Fag: 700
Treatment Failure
Antiviral treatment
Baseline (configuration management)
Aged
Sweden
resistance-associated substitution
Baseline resistance
Norway
business.industry
sustained virologic response
Gastroenterology
Middle Aged
Hepatitis C
VDP::Medical disciplines: 700
Multicenter study
030220 oncology & carcinogenesis
Drug Therapy
Combination
Female
030211 gastroenterology & hepatology
business
Direct acting
Popis: 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 (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.
Databáze: OpenAIRE
Externí odkaz: