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Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches

2014; Wiley; Volume: 86; Issue: 10 Linguagem: Inglês

10.1002/jmv.24015

1096-9071

Isabel Maria Vicente Guedes de Carvalho-Mello, Rafael Alves da Silva, Polyana A. Vasconcelos-Medeiros de Souza, Edvaldo F. da Silva, Daniel Ferraz de Campos Mazo, Flair José Carrilho, Artur T. L. Queiroz, Mário G. Pessôa,

HIV/AIDS drug development and treatment

Journal of Medical VirologyVolume 86, Issue 10 p. 1714-1721 Research Article Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches Isabel M.V.G. de Carvalho, Isabel M.V.G. de Carvalho Viral Imunology, Butantan Institute, Avenida Doutor Vital Brasil, São Paulo, Brazil Applied Molecular Hepatology Laboratory (LHeMA), Hepatitis Sector, Gastroenterology Division, São Paulo Federal University, São Paulo, BrazilSearch for more papers by this authorRafael Alves, Rafael Alves Applied Molecular Hepatology Laboratory (LHeMA), Hepatitis Sector, Gastroenterology Division, São Paulo Federal University, São Paulo, BrazilSearch for more papers by this authorPolyana A. Vasconcelos-Medeiros de Souza, Polyana A. Vasconcelos-Medeiros de Souza Viral Imunology, Butantan Institute, Avenida Doutor Vital Brasil, São Paulo, BrazilSearch for more papers by this authorEdvaldo F. da Silva, Edvaldo F. da Silva Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, BrazilSearch for more papers by this authorDaniel Mazo, Daniel Mazo Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, BrazilSearch for more papers by this authorFlair J. Carrilho, Flair J. Carrilho Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, BrazilSearch for more papers by this authorArtur T.L. Queiroz, Corresponding Author Artur T.L. Queiroz Immunoparasitology Laboratory, Gonçalo Moniz Research Center (FIOCRUZ), Salvador, BA, Brazil Correspondence to: Artur T.L. de Queiroz, Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, Brazil. E-mail: [email protected]Search for more papers by this authorMário G. Pessoa, Mário G. Pessoa Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, BrazilSearch for more papers by this author Isabel M.V.G. de Carvalho, Isabel M.V.G. de Carvalho Viral Imunology, Butantan Institute, Avenida Doutor Vital Brasil, São Paulo, Brazil Applied Molecular Hepatology Laboratory (LHeMA), Hepatitis Sector, Gastroenterology Division, São Paulo Federal University, São Paulo, BrazilSearch for more papers by this authorRafael Alves, Rafael Alves Applied Molecular Hepatology Laboratory (LHeMA), Hepatitis Sector, Gastroenterology Division, São Paulo Federal University, São Paulo, BrazilSearch for more papers by this authorPolyana A. Vasconcelos-Medeiros de Souza, Polyana A. Vasconcelos-Medeiros de Souza Viral Imunology, Butantan Institute, Avenida Doutor Vital Brasil, São Paulo, BrazilSearch for more papers by this authorEdvaldo F. da Silva, Edvaldo F. da Silva Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, BrazilSearch for more papers by this authorDaniel Mazo, Daniel Mazo Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, BrazilSearch for more papers by this authorFlair J. Carrilho, Flair J. Carrilho Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, BrazilSearch for more papers by this authorArtur T.L. Queiroz, Corresponding Author Artur T.L. Queiroz Immunoparasitology Laboratory, Gonçalo Moniz Research Center (FIOCRUZ), Salvador, BA, Brazil Correspondence to: Artur T.L. de Queiroz, Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, Brazil. E-mail: [email protected]Search for more papers by this authorMário G. Pessoa, Mário G. Pessoa Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, BrazilSearch for more papers by this author First published: 11 July 2014 https://doi.org/10.1002/jmv.24015Citations: 15 The authors declare no competing interests. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Several new direct-acting antiviral (DAA) drugs are being developed or are already approved for the treatment of chronic hepatitis C virus (HCV) infection. HCV variants presenting drug-resistant phenotypes were observed both in vitro and during clinical trials. The aim of this study was to characterize amino acid changes at positions previously associated with resistance in the NS3 protease in untreated Brazilian patients infected with HCV genotypes 1a and 1b. Plasma samples from 171 untreated Brazilian patients infected with HCV were obtained from the Department of Gastroenterology of Clinics Hospital (HCFMUSP) in São Paulo, Brazil. Nested PCR and Sanger sequencing were used to obtain genetic information on the NS3 protein. Bioinformatics was used to confirm subtype information and analyze frequencies of resistance mutations. The results from the genotype analysis using non-NS3 targeted methods were at variance with those obtained from the NS3 protease phylogenetic analyses. It was found that 7.4% of patients infected with HCV genotype 1a showed the resistance-associated mutations V36L, T54S, Q80K, and R155K, while 5.1% of patients infected with HCV genotype 1b had the resistance-associated mutations V36L, Q41R, T54S, and D168S. Notably, codons at positions 80 and 155 differed between samples from Brazilian patient used in this study and global isolates. The present study demonstrates that genotyping methods targeting the NS3 protein showed a difference of results when compared to mainstream methodologies (INNO-LiPA and polymerase sequencing). The resistance mutations present in untreated patients infected with HCV and codon composition bias by geographical location warrant closer examination. J. Med. Virol. 86: 1714–1721, 2014. © 2014 Wiley Periodicals, Inc. REFERENCES Alves R, Queiroz AT, Pessoa MG, da Silva EF, Mazo DF, Carrilho FJ, Carvalho-Filho RJ, de Carvalho IM. 2013. 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