Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

• Author(s): Ruben, Brandão, ; Rute, Marcelino, ; Goncalves, Maria de Fátima ; Diogo, Isabel ; Carvalho, A P ; Cabanas, Joaquim ; Costa, Inês ; Brogueira, Pedro ; Ventura, F ; Miranda , Ana Cláudia ; Mansinho, Kamal ; Gomes, P
• Date: 2018
• Persistent ID: http://hdl.handle.net/10362/116851
• Origin: Repositório Institucional da UNL
• Subject(s): Direct-acting antivirals; Hepatitis C virus; NS5A; NS5B; Resistance-associated substitutions; SDG 3 - Good Health and Well-being
• Document Type: Journal article
• Language: English
• Contributor(s): TB, HIV and opportunistic diseases and pathogens (THOP); Global Health and Tropical Medicine (GHTM); Instituto de Higiene e Medicina Tropical (IHMT); NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); RUN

Description

This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).