Hepatitis C is the liver inflammation caused by the infection of Hepatitis C virus (HCV), a positive single stranded RNA virus from the Flaviviridae family. The high replication rate, associated to the lack of proof-reading activity of the viral polymerase NS5B, leads to high mutation rate in the viral genome. As a result, the virus is classified into 7 different genotypes. In Brazil, genotype 1 is the most prevalent followed by genotype 3. The most recent treatment for HCV infected patients, in Brazil, is based on the administration of three Direct Acting Antivirals (DAAs), Simeprevir, an NS3 inhibitor; Daclatasvir, an NS5A inhibitor; and Sofosbuvir, an NS5B inhibitor. This therapy presents high Sustained Virological Response (SVR) to all genotypes when compared to previous treatment. Still, genotype 3 infected patients showed to be the most difficult to treat. There are many studies showing the presence of resistance associated mutations against these DAAs, however, the majority of them are with genotype 1. Genotype 3 correspond to about 30% of HCV cases in Brazil and literature has scarce data about resistance mutations specific to this genotype. Thus, our study aims to investigate mutations in genotype 3 that potentially confers resistance to the treatment with Daclatasvir, also testing them to different NS5A direct acting antivirals.
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