Prevalence of naturally occurring amino acid substitutions associated with resistance to hepatitis C virus NS3/NS4A protease inhibitors in São Paulo state.

Autor: Moreira RC; Laboratory of Viral Hepatitis, Virology Center, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 355, Cerqueira César, São Paulo, SP, CEP 01246-902, Brazil. regina.moreira7@gmail.com., de Torres Santos AP; Laboratory of Viral Hepatitis, Virology Center, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 355, Cerqueira César, São Paulo, SP, CEP 01246-902, Brazil.; Divisão de Laboratório Central, Laboratório de Imunologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil., Lisboa-Neto G; Department of Infectious Diseases, School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Mendes-Corrêa MCJ; Department of Infectious Diseases, School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Lemos MF; Laboratory of Viral Hepatitis, Virology Center, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 355, Cerqueira César, São Paulo, SP, CEP 01246-902, Brazil., Malta FM; Laboratory of Tropical Gastroenterology and Hepatology 'João de Queiroz and Castorina Bettencourt Alves'-LIM 07-Institute of Tropical Medicine Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Santana RAF; Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil., Dastoli GTF; Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil., de Castro VFD; Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil., Pinho JRR; Laboratory of Tropical Gastroenterology and Hepatology 'João de Queiroz and Castorina Bettencourt Alves'-LIM 07-Institute of Tropical Medicine Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.; Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
Jazyk: angličtina
Zdroj: Archives of virology [Arch Virol] 2018 Oct; Vol. 163 (10), pp. 2757-2764. Date of Electronic Publication: 2018 Jun 30.
DOI: 10.1007/s00705-018-3920-9
Abstrakt: Hepatitis C (HCV)-infected patients are treated with direct-acting antiviral agents (DAAs) in highly effective, well-tolerated, all-oral regimens. However, naturally occurring resistance-associated amino acid substitutions (RASs) may be selected during treatment. This study aimed to screen naturally occurring RASs NS3/NS4A inhibitors (PIs). Samples were obtained from DAA naïve patients, living in São Paulo state, Brazil. Screening for RASs in the HCV NS3 region was conducted in 859 samples from HCV-infected patients, of which 425 and 434 samples were subtype 1a and 1b, respectively. HCV-RNA was extracted, amplified, and sequenced. The overall prevalence of RASs to HCV PIs was 9.4%. The following RASs were observed in HCV-1a subtype infected patients: V36L (2.6%), T54S (1.6%), V55I/A (1.2% / 8.9%, respectively), Q80K (2.1%), R155K (0.5%), and D168E (0.2%); and in HCV-1b infected patients: V36L (0.7%), T54A/S (0.2% and 0.5%, respectively), V55A (0.5%), Q80K (0.2%), D168E (1.6%), and M175L (0.5%). HCV 1a infected subjects had higher serum viral load than that seen in patients infected with HCV 1b. There was no difference between the proportions of NS3 RASs with regards to geographic distribution within the investigated areas. These findings should be supported by additional studies in Brazil to help in the formation of local clinical guidelines for managing hepatitis C.
Databáze: MEDLINE