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

Grant number: 16/03807-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2017
Effective date (End): July 31, 2020
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Paula Rahal
Grantee:Guilherme Rodrigues Fernandes Campos
Home 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
Associated scholarship(s):18/04678-5 - Analysis of Hepatitis C virus genotype 3 resistance to direct acting antivirals, BE.EP.DR

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)

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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, . (18/05974-7, 18/05975-3, 16/03807-0)
WARD, JOSEPH C.; BOWYER, SEBASTIAN; CHEN, SHUCHENG; CAMPOS, GUILHERME RODRIGUES FERNANDES; RAMIREZ, SANTSEHARAY; BUKH, JENS; HARRIS, MARK. Insights into the unique characteristics of hepatitis C virus genotype 3 revealed by development of a robust sub-genomic DBN3a replicon. JOURNAL OF GENERAL VIROLOGY, v. 101, n. 11, p. 1182-1190, . (16/03807-0, 18/04678-5)
FERNANDES CAMPOS, GUILHERME RODRIGUES; WARD, JOSEPH; CHEN, SHUCHENG; BITTAR, CINTIA; VILELA RODRIGUES, JOAO PAULO; CANDOLO MARTINELLI, ANA DE LOURDES; SOUZA, FERNANDA FERNANDES; LEIRA PEREIRA, LEONARDO REGIS; RAHAL, PAULA; HARRIS, MARK. A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir. JOURNAL OF GENERAL VIROLOGY, v. 102, n. 1, . (18/04678-5, 16/03807-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CAMPOS, Guilherme Rodrigues Fernandes. Study of resistance mutations to treatment with direct action drugs in patients infected with hepatitis C virus genotype 3. 2020. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto São José do Rio Preto.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.