Prevalence of Naturally Occurring Resistance Associated Substitutions in NS3/4AProtease Inhibitors in Iranian HCV/HIV Infected Patients.

Abstract

Hepatitis C virus (HCV) acts in the host as a complicated mixture of related variants with the potency to genetically escape host immune responses. Direct acting antivirals (DAAs) have been approved for HCV treatment with shorter duration, better cure rates and lower side effects. However, naturally occurring resistance associated substitutions (RASs) create some obstacles to this antiviral therapy success. In this study, we aimed at the determination of the naturally occurring NS3/4A RASs in HCV/human immunodeficiency virus (HIV)infected patients. A total of 120 DAA-naïve HCV-HIV co-infected patients were included. HCV NS3/4Agenome region was amplified with PCR and mutation analysis was performed by Sanger sequencing technique. The amino acid sequence diversity of the region was analyzed using geno2pheno HCV. Phylogenetic analysis showed that 73 cases were infected by 3a and 47 subjects by subtype1a. The overall RASs among studied subjects were observed in 6 (5%) individuals from 120 studied cases who were infected with HCV 1a. V36M/L, Q80L, S122G/L, R155T/G, A156S, D168Y/N and S174A/N/T mutations were detected in this study. Although the prevalence of RASs was totally low in this study, the presence of several cases of double and triple mutants among this population suggests prior evaluation of protease inhibitors related mutations before initiation of standard treatment and also an investigation on a large population could be of high value.