NS5A resistance – associated substitutions in chronic hepatitis C patients with direct acting antiviral treatment failure in Turkey

• Published in: International journal of infectious diseases 2020-06, Vol.95, p.84-89
• Main Authors: Sayan, Murat, Yıldırım, Figen Sarıgül, Akhan, Sıla, Yıldırım, Arzu Altunçekiç, Şirin, Göktuğ, Cabalak, Mehmet, Demir, Mehmet, Can, Selver, Ersöz, Gülden, Altıntaş, Engin, Ensaroğlu, Fatih, Akbulut, Ayhan, Şener, Alper, Deveci, Aydın
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antiviral Agents - therapeutic use; Drug Resistance, Viral - genetics; Female; Genetic Variation; Genotyping Techniques; Hepacivirus - drug effects; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Humans; Longitudinal Studies; Male; Middle Aged; NS-5 protein; Prospective Studies; Recurrence; Sequence analysis; Treatment Failure; Turkey; Viral Nonstructural Proteins - genetics
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2020.03.061

•The primary objective of this study was to characterize the real-life presence of clinically relevant RASs in the NS5A gene in CHC patients whose DAA regimen has failed.•The study enrolled with CHC patients who experienced failure with DAA regimen as the prospective longitudinal cohort between July 2017 – September 2019.•Genotypic resistance testing was performed via the viral population sequencing method (NS5A amino acid position between 1935.–2237.).•The Geno2pheno HCV tool was used for the RAS analysis.•The most frequent failure category was relapse (88%) followed by non-responder (12%) between study patients.•For a total of 36% of patients, RASs was detected in NS5A, Y93H was the most detected RAS in GT1b infected patients (89%). Chronic hepatitis C (CHC) is now a more curable disease with new direct acting antivirals (DAA). Although high sustained virologic response rates, failures still occur in DAA regimens. Our objective in this study was to characterize the real-life presence of clinically relevant resistance – associated substitutions (RASs) in the HCV NS5A gene in CHC patients whose DAA regimen has failed. The study enrolled 53 CHC patients who experienced failure with DAA regimen as the prospective longitudinal cohort between 2017–2019. Genotypic resistance testing was performed via the viral population sequencing method and The Geno2pheno HCV tool was used for RAS analysis. The most frequent failure category was relapse (88%) followed by non-responder (12%). For a total of 36% of patients, RASs was detected in NS5A, Y93H was the most detected RAS in GT1b infected patients (89%). This study establishes an HCV failure registry for Turkey in which samples were combined with clinical, virologic and molecular data of adult patients whose DAA therapy failed. RASs can occur in CHC patients with DAA treatment failures. Evaluation of RAS after DAA failure is very important before re-treatment is initiated to prevent virologic failure.