Abstract
BackgroundHepatitis C virus (HCV) non-structural protein 5A (NS5A) inhibitors have been recently developed to inhibit NS5A activities and have been approved for the treatment of HCV infection. However the drawback of these direct acting antivirals (DAAs) is the emergence of resistance mutations. The prevalence of such mutations conferring resistance to HCV-NS5A inhibitors before treatment has not been investigated so far in the Tunisian population. The aim of this study was to detect HCV variants resistant to HCV-NS5A inhibitors in hepatitis C patients infected with HCV genotype 1 before any treatment with NS5A inhibitors.MethodsAmplification and direct sequencing of the HCV NS5A region was carried out on 112 samples from 149 untreated patients.ResultsIn genotype 1a strains, amino acid substitutions conferring resistance to NS5A inhibitors (M28V) were detected in 1/7 (14.2 %) HCV NS5A sequences analyzed. In genotype 1b, resistance mutations in the NS5A region (R30Q; L31M; P58S and Y93H) were observed in 17/105 (16.2 %) HCV NS5A sequences analyzed. R30Q and Y93H (n = 6; 5.7 %) predominated over P58S (n = 4; 3.8 %) and L31M (n = 3; 2.8 %).ConclusionsMutations conferring resistance to HCV NS5A inhibitors are frequent in treatment-naïve Tunisian patients infected with HCV genotype 1b. Their influence in the context of DAA therapies has not been fully investigated and should be taken into consideration.
Highlights
Hepatitis C virus (HCV) non-structural protein 5A (NS5A) inhibitors have been recently developed to inhibit NS5A activities and have been approved for the treatment of HCV infection
This treatment is associated with a high longterm response rate in patients infected with HCV genotype 2 and 3, whereas a sustained virologic response (SVR) can be achieved only in 50 % of patients infected with HCV genotype 1 [10,11,12]
The aim of this study was to investigate the natural prevalence of mutations conferring resistance to NS5A inhibitors in clinical strains from treatment-naïve Tunisian patients infected with HCV genotype 1
Summary
Hepatitis C virus (HCV) non-structural protein 5A (NS5A) inhibitors have been recently developed to inhibit NS5A activities and have been approved for the treatment of HCV infection. HCV has infected 180 million people, approximately 3 % of the world’s population [2] It is an enveloped positive-strand RNA virus and is the only member of the Hepacivirus genus of the Flaviviridae family [3]. The current standard therapy in Tunisia consists of pegylated alpha interferon (PEG-IFNα) combined with ribavirin (RBV), a nucleoside analogue, for 24–48 weeks [9]. This treatment is associated with a high longterm response rate in patients infected with HCV genotype 2 and 3, whereas a sustained virologic response (SVR) can be achieved only in 50 % of patients infected with HCV genotype 1 [10,11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
