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

Archives of Virology volume 163, pages 2757–2764 (2018)Cite this article

Abstract

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.

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Funding

This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP (Grant number: 2017/01809-9).

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Affiliations

  1. Laboratory of Viral Hepatitis, Virology Center, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 355, Cerqueira César, São Paulo, SP, CEP 01246-902, Brazil

    Regina Célia Moreira, Ana Paula de Torres Santos & Marcilio Figueiredo Lemos

  2. Divisão de Laboratório Central, Laboratório de Imunologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil

    Ana Paula de Torres Santos

  3. Department of Infectious Diseases, School of Medicine, University of São Paulo, São Paulo, SP, Brazil

    Gaspar Lisboa-Neto & Maria Cássia Jacintho Mendes-Corrêa

  4. 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

    Fernanda Mello Malta & João Renato Rebello Pinho

  5. Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil

    Rúbia Anita Ferraz Santana, Gregório Tadeu Fernando Dastoli, Vanessa Fusco Duarte de Castro & João Renato Rebello Pinho

Authors
  1. Regina Célia Moreira
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  2. Ana Paula de Torres Santos
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  3. Gaspar Lisboa-Neto
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  4. Maria Cássia Jacintho Mendes-Corrêa
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  5. Marcilio Figueiredo Lemos
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  6. Fernanda Mello Malta
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  7. Rúbia Anita Ferraz Santana
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  8. Gregório Tadeu Fernando Dastoli
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  9. Vanessa Fusco Duarte de Castro
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  10. João Renato Rebello Pinho
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Corresponding author

Correspondence to Regina Célia Moreira.

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Conflict of interest

João Renato Rebello Pinho is an employee of Albert Einstein Medicina Diagnóstica, São Paulo, Brazil. All other authors who took part in this study declare that they have no conflicts of interest or disclosures with respect to the manuscript.

Ethical standards

The procedures described in this study were only initiated after obtaining approval from the ethics committees of the participating institutions. This study was approved by the Ethical Committee in Research at the Instituto Adolfo Lutz (CEPIAL #1.040.338-2015).

Additional information

Communicated by Michael Carpenter.

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Moreira, R.C., de Torres Santos, A.P., Lisboa-Neto, G. et al. Prevalence of naturally occurring amino acid substitutions associated with resistance to hepatitis C virus NS3/NS4A protease inhibitors in São Paulo state. Arch Virol 163, 2757–2764 (2018). https://doi.org/10.1007/s00705-018-3920-9

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  • DOI: https://doi.org/10.1007/s00705-018-3920-9