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Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil

Hepatitis C virus (HCV) is responsible for more than 180 million infections worldwide, and about 80 % of infections are reported in Low and Middle-income countries (LMICs). Therapy is based on the administration of interferon (INF), ribavirin (RBV) or more recently Direct-Acting Antivirals (DAAs). H...

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Autores principales: Adeboyejo, Kazeem, Grosche, Victória Riquena, José, Diego Pandeló, Ferreira, Giulia Magalhães, Shimizu, Jacqueline Farinha, King, Barnabas J., Tarr, Alexander W., Soares, Márcia Maria Costa Nunes, Ball, Jonathan K., McClure, C. Patrick, Jardim, Ana Carolina Gomes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Microbiology Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175972/
https://www.ncbi.nlm.nih.gov/pubmed/35693474
http://dx.doi.org/10.1099/acmi.0.000326
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author Adeboyejo, Kazeem
Grosche, Victória Riquena
José, Diego Pandeló
Ferreira, Giulia Magalhães
Shimizu, Jacqueline Farinha
King, Barnabas J.
Tarr, Alexander W.
Soares, Márcia Maria Costa Nunes
Ball, Jonathan K.
McClure, C. Patrick
Jardim, Ana Carolina Gomes
author_facet Adeboyejo, Kazeem
Grosche, Victória Riquena
José, Diego Pandeló
Ferreira, Giulia Magalhães
Shimizu, Jacqueline Farinha
King, Barnabas J.
Tarr, Alexander W.
Soares, Márcia Maria Costa Nunes
Ball, Jonathan K.
McClure, C. Patrick
Jardim, Ana Carolina Gomes
author_sort Adeboyejo, Kazeem
collection PubMed
description Hepatitis C virus (HCV) is responsible for more than 180 million infections worldwide, and about 80 % of infections are reported in Low and Middle-income countries (LMICs). Therapy is based on the administration of interferon (INF), ribavirin (RBV) or more recently Direct-Acting Antivirals (DAAs). However, amino acid substitutions associated with resistance (RAS) have been extensively described and can contribute to treatment failure, and diagnosis of RAS requires considerable infrastructure, not always locally available. Dried serum spots (DSS) sampling is an alternative specimen collection method, which embeds drops of serum onto filter paper to be transported by posting to a centralized laboratory. Here, we assessed feasibility of genotypic analysis of HCV from DSS in a cohort of 80 patients from São Paulo state Brazil. HCV RNA was detected on DSS specimens in 83 % of samples of HCV infected patients. HCV genotypes 1a, 1b, 2a, 2c and 3a were determined using the sequence of the palm domain of NS5B region, and RAS C316N/Y, Q309R and V321I were identified in HCV 1b samples. Concerning therapy outcome, 75 % of the patients who used INF +RBV as a previous protocol of treatment did not respond to DAAs, and 25 % were end-of-treatment responders. It suggests that therapy with INF plus RBV may contribute for non-response to a second therapeutic protocol with DAAs. One patient that presented RAS (V321I) was classified as non-responder, and combination of RAS C316N and Q309R does not necessarily imply in resistance to treatment in this cohort of patients. Data presented herein highlights the relevance of studying circulating variants for a better understanding of HCV variability and resistance to the therapy. Furthermore, the feasibility of carrying out genotyping and RAS phenotyping analysis by using DSS card for the potential of informing future treatment interventions could be relevant to overcome the limitations of processing samples in several location worldwide, especially in LMICs.
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spelling pubmed-91759722022-06-09 Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil Adeboyejo, Kazeem Grosche, Victória Riquena José, Diego Pandeló Ferreira, Giulia Magalhães Shimizu, Jacqueline Farinha King, Barnabas J. Tarr, Alexander W. Soares, Márcia Maria Costa Nunes Ball, Jonathan K. McClure, C. Patrick Jardim, Ana Carolina Gomes Access Microbiol Research Articles Hepatitis C virus (HCV) is responsible for more than 180 million infections worldwide, and about 80 % of infections are reported in Low and Middle-income countries (LMICs). Therapy is based on the administration of interferon (INF), ribavirin (RBV) or more recently Direct-Acting Antivirals (DAAs). However, amino acid substitutions associated with resistance (RAS) have been extensively described and can contribute to treatment failure, and diagnosis of RAS requires considerable infrastructure, not always locally available. Dried serum spots (DSS) sampling is an alternative specimen collection method, which embeds drops of serum onto filter paper to be transported by posting to a centralized laboratory. Here, we assessed feasibility of genotypic analysis of HCV from DSS in a cohort of 80 patients from São Paulo state Brazil. HCV RNA was detected on DSS specimens in 83 % of samples of HCV infected patients. HCV genotypes 1a, 1b, 2a, 2c and 3a were determined using the sequence of the palm domain of NS5B region, and RAS C316N/Y, Q309R and V321I were identified in HCV 1b samples. Concerning therapy outcome, 75 % of the patients who used INF +RBV as a previous protocol of treatment did not respond to DAAs, and 25 % were end-of-treatment responders. It suggests that therapy with INF plus RBV may contribute for non-response to a second therapeutic protocol with DAAs. One patient that presented RAS (V321I) was classified as non-responder, and combination of RAS C316N and Q309R does not necessarily imply in resistance to treatment in this cohort of patients. Data presented herein highlights the relevance of studying circulating variants for a better understanding of HCV variability and resistance to the therapy. Furthermore, the feasibility of carrying out genotyping and RAS phenotyping analysis by using DSS card for the potential of informing future treatment interventions could be relevant to overcome the limitations of processing samples in several location worldwide, especially in LMICs. Microbiology Society 2022-03-02 /pmc/articles/PMC9175972/ /pubmed/35693474 http://dx.doi.org/10.1099/acmi.0.000326 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
spellingShingle Research Articles
Adeboyejo, Kazeem
Grosche, Victória Riquena
José, Diego Pandeló
Ferreira, Giulia Magalhães
Shimizu, Jacqueline Farinha
King, Barnabas J.
Tarr, Alexander W.
Soares, Márcia Maria Costa Nunes
Ball, Jonathan K.
McClure, C. Patrick
Jardim, Ana Carolina Gomes
Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil
title Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil
title_full Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil
title_fullStr Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil
title_full_unstemmed Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil
title_short Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil
title_sort simultaneous determination of hcv genotype and ns5b resistance associated substitutions using dried serum spots from são paulo state, brazil
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175972/
https://www.ncbi.nlm.nih.gov/pubmed/35693474
http://dx.doi.org/10.1099/acmi.0.000326
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