NS5A Resistance Associated Mutations to Daclatasvir in Hepatitis C Virus Genotype 3a Treatment Naive and SOF/DCV Treatment Failure Patients
NS5A Resistance Associated Mutations to Daclatasvir in Hepatitis C Virus Genotype 3a Treatment Naive and SOF/DCV Treatment Failure Patients
Saima Younas and Aleena Sumrin*
ABSTRACT
Pakistan has the second highest hepatitis C virus (HCV) prevalence with seroprevalence of 4.5-8.2%, with genotype 3a being most frequently circulating HCV genotype. Current treatment strategies for HCV are based on direct acting antivirals (DAAs), despite high efficacy of antivirals, still therapy failure has been reported in 5-10% cases due to resistance mutations of amino acids. This study was aimed to analyze clinically important resistance associated mutations (RAMs) to daclatasvir (DCV) in HCV GT-3a NS5A region in treatment naive and DAA treatment experienced patients, to understand their role in treatment failure. Patients samples and data was collected on prescribed questionnaire. Viral nucleic acid was isolated and amplified by gene specific primers followed by sequencing of NS5A region by Sanger method. Amino acid substitutions were identified by using Geno2Pheno tool. Hepatitis c virus genotype 3a was most prevalent genotype in the study group. Successfully sequenced patients were divided into two group based on their treatment history, as treatment naive and experienced groups. Both groups were analyzed for detection of amino acid mutations at positions 28, 30, 31, 58 and 93. A30T was detected in 7.6%, Y93H in 15.6% P58T as 7.6% while S98G was found in 23% treated patients. However, these mutations were not detected in any of treatment naive patients. Some mutations were identified in both treatment naive and experienced groups i.e., A21T, T64A, H85Y, S103P, D172E, H180N, T183A/V, and E137G. Mutations at position 62 was most commonly detected found at the frequency of 83.8% and 84.6% in treatment naive and experienced patients respectively. While mutations at position M28 and L31 were not identified in both groups of current study. Mutations present in both treatment naive as well as in treatment experienced groups suggesting they have no role in DCV resistance, while identification of A30T, Y93H, P58T and S98G in treated patients suggests that DCV RAMs are circulating in Pakistani HCV GT-3a DAAs treated patients, leading to resistance development and treatment failure. Identification of these mutations is important especially in treatment failure patients to design re-treatment strategies.
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