Study of resistance mutations to treatment with Directly Acting antivirals in patients infected with hepatitis C virus genotype 3

Abstract

Hepatitis C is a liver inflammation caused by Hepatitis C Virus (HCV), a positive single stranded RNA virus belonging to Flaviviridae family. According to the World Health Organization (WHO), approximately 185 million people are infected by HCV, with 350 thousand deaths related to this disease around world. In Brazil, the number is around 1.4 and 1.7 million people infected. There is no vaccine against HCV, and the latest treatment, based in Interferon and direct acting protease inhibitors, Boceprevir and Telaprevir, has a high cost and the sustained virological response (SVR) varies according to the viral genotype. Recently, the use of second generation direct acting antivirals, Simeprevir, Sofosbuvir and Daclatasvir, was approved. The administration of these medicines led to an improvement of SVR, for all genotypes. However, genotype 3 presented the lowest response when compared to the other genotypes. In Brazil, the clinical protocol and therapeutic guidelines of Health Ministry, published in July 2015, indicates the use of Sofosbuvir and Daclatasvir for treatment of genotype 3 infected patients. Some studies associate lower response to treatment with resistance mutations in viral genome. In this way, this study aims to investigate viral resistance mutations already known and describe new mutations in patients infected by HCV genotype 3 who do not respond to treatment with Sofosbuvir and Daclatasvir, evaluating the replicative behavior of these mutations in cell culture. (AU)