Survey of the frequency of resistance mutations to direct acting antivirals in the NS3 and NS5A regions of Hepatitis C Virus (HCV) genotype 1B

• Grant number: 18/05974-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2018
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Paula Rahal
• Grantee: Nayara Nathie Marques
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Hepatitis C is an inflammation of the liver that affects about 170 million of people all over the world and causes the death of 350,000 people every year. In Brazil, it is estimated to affect around 1.23% of the population. The disease is caused by the Hepatitis C Virus (HCV), an enveloped virus from the Flaviviridae family and Hepacivirus gender with a single stranded positive RNA genome of approximately 9.6Kb. Due to the high replication rate, associated with the lack of proofreading activity of the NS5B viral polymerase, the virus can be classified into seven different genotypes and several subtypes. In addition, HCV has the characteristic of circulate in the host as a pool of viral variants with a genetic divergence of up to 5%, called quasispecies. There is no vaccine against HCV, and the current treatment is based on the use of the Direct Action Antivirals (DAAs) Simeprevir (protease inhibitor NS3), Sofosbuvir (NS5B polymerase inhibitor) and Daclatavir (NS5A inhibitor), associated or not with peg-IFN and Ribavirin. This therapy greatly elevated the values of Sustained Virological Response (SVR), but several mutations associated with resistance have been already described. This characteristic of high genetic variability, associated with the selective pressure exerted by the treatment, allows the emergence of mutations associated with resistance in the target regions of the DAAs, resulting in decrease of the SVR and consequently evasion to treatment. This study aims to observe the prevalence of resistance mutations in the NS3 and NS5A viral regions in patients infected by hepatitis C virus genotype 1b and under treatment with Simeprevir or Daclatasvir. This will allow us to understand the frequency of these mutations in the studied population and assist in the therapeutic targeting to reduce the treatment evasion.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

AGUIAR, BRUNA FORTE; CAMPOS, GUILHERME RODRIGUES FERNANDES; RODRIGUES, JOAO PAULO VILELA; MARQUES, NAYARA NATHIE; MOLINA, BARBARA FLORIANO; BITTAR, CINTIA; SOUZA, FERNANDA FERNANDES; MARTINELLI, ANA DE LOURDES CANDOLO; RAHAL, PAULA; PEREIRA, LEONARDO REGIS LEIRA. Baseline resistance associated substitutions in HCV genotype 1 infected cohort treated with Simeprevir, Daclatasvir and Sofosbuvir in Brazil. CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY, v. 44, n. 3, p. 329-339, JUN 2020. (18/05974-7, 18/05975-3, 16/03807-0)