Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antivirals
ABSTRACT: Background: Hepatitis C virus (HCV) is a global public health problem. Second-generation direct-acting antivirals targeting non-structural regions on the viral genome are the cornerstone for treatment of chronic infection. However, resistance-associated variants (RAVs) have been reported...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-02-01
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| Series: | International Journal of Infectious Diseases |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1201971221012170 |
| _version_ | 1819175845452840960 |
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| author | Bianca Catarina Azeredo Cabral Juliene Antonio Ramos Amanda Laryssa de Melo Silveira Érica Ramos dos Santos Nascimento Selma Baía Ferreira Henrique Sérgio Moraes Coelho Rodrigo Soares Moura-Neto Cristiane Alves Villela-Nogueira Luísa Hoffmann Rosane Silva |
| author_facet | Bianca Catarina Azeredo Cabral Juliene Antonio Ramos Amanda Laryssa de Melo Silveira Érica Ramos dos Santos Nascimento Selma Baía Ferreira Henrique Sérgio Moraes Coelho Rodrigo Soares Moura-Neto Cristiane Alves Villela-Nogueira Luísa Hoffmann Rosane Silva |
| author_sort | Bianca Catarina Azeredo Cabral |
| collection | DOAJ |
| description | ABSTRACT: Background: Hepatitis C virus (HCV) is a global public health problem. Second-generation direct-acting antivirals targeting non-structural regions on the viral genome are the cornerstone for treatment of chronic infection. However, resistance-associated variants (RAVs) have been reported to be associated with therapeutic failure. The aim of this study was to assess the frequency of variants, including RAVs, in the NS3, NS5A and NS5B regions at baseline in Brazilian patients with chronic hepatitis C with HCV genotypes 1a, 1b and 3a. Methods: Serum samples from 13 patients were used to obtain viral RNA. Massively parallel sequencing was performed using genotype-specific amplicons and a panel of Ampliseq technology for all genotypes. Results: Several non-synonymous substitutions were detected at baseline for 11 responders and pre-/post-treatment for two non-responders. HCV genotype 3a was found to have significantly more non-synonymous substitutions than HCV genotype 1 in the NS3 and NS5A regions. Analyses were conducted using quantitative and qualitative inter- and intrapatient comparisons. Variants that confer resistance to the treatment used by the patients were found in both responders and non-responders. Conclusions: A wide frequency distribution of RAVs was found at baseline, and this did not interfere with the achievement of a sustained response. Evaluation of the presence of RAVs requires additional study in order to determine clinical relevance. |
| first_indexed | 2024-12-22T21:01:20Z |
| format | Article |
| id | doaj.art-ec7863321d564f01a41ba65e1b7ef678 |
| institution | Directory Open Access Journal |
| issn | 1201-9712 |
| language | English |
| last_indexed | 2024-12-22T21:01:20Z |
| publishDate | 2022-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Infectious Diseases |
| spelling | doaj.art-ec7863321d564f01a41ba65e1b7ef6782022-12-21T18:12:49ZengElsevierInternational Journal of Infectious Diseases1201-97122022-02-01115171177Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antiviralsBianca Catarina Azeredo Cabral0Juliene Antonio Ramos1Amanda Laryssa de Melo Silveira2Érica Ramos dos Santos Nascimento3Selma Baía Ferreira4Henrique Sérgio Moraes Coelho5Rodrigo Soares Moura-Neto6Cristiane Alves Villela-Nogueira7Luísa Hoffmann8Rosane Silva9Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de Biotecnologia, Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilServiço de Hepatologia, Hospital Universitário Clementino Fraga Filho e Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilServiço de Hepatologia, Hospital Universitário Clementino Fraga Filho e Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilServiço de Hepatologia, Hospital Universitário Clementino Fraga Filho e Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilInstituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilServiço de Hepatologia, Hospital Universitário Clementino Fraga Filho e Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de Biotecnologia, Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Corresponding author. 373, Carlos Chagas Filho St, Room G1-050, Ilha do Fundão, Rio de Janeiro 21941-902, BrazilABSTRACT: Background: Hepatitis C virus (HCV) is a global public health problem. Second-generation direct-acting antivirals targeting non-structural regions on the viral genome are the cornerstone for treatment of chronic infection. However, resistance-associated variants (RAVs) have been reported to be associated with therapeutic failure. The aim of this study was to assess the frequency of variants, including RAVs, in the NS3, NS5A and NS5B regions at baseline in Brazilian patients with chronic hepatitis C with HCV genotypes 1a, 1b and 3a. Methods: Serum samples from 13 patients were used to obtain viral RNA. Massively parallel sequencing was performed using genotype-specific amplicons and a panel of Ampliseq technology for all genotypes. Results: Several non-synonymous substitutions were detected at baseline for 11 responders and pre-/post-treatment for two non-responders. HCV genotype 3a was found to have significantly more non-synonymous substitutions than HCV genotype 1 in the NS3 and NS5A regions. Analyses were conducted using quantitative and qualitative inter- and intrapatient comparisons. Variants that confer resistance to the treatment used by the patients were found in both responders and non-responders. Conclusions: A wide frequency distribution of RAVs was found at baseline, and this did not interfere with the achievement of a sustained response. Evaluation of the presence of RAVs requires additional study in order to determine clinical relevance.http://www.sciencedirect.com/science/article/pii/S1201971221012170Hepatitis CMassively parallel sequencingRAVsTreatment response |
| spellingShingle | Bianca Catarina Azeredo Cabral Juliene Antonio Ramos Amanda Laryssa de Melo Silveira Érica Ramos dos Santos Nascimento Selma Baía Ferreira Henrique Sérgio Moraes Coelho Rodrigo Soares Moura-Neto Cristiane Alves Villela-Nogueira Luísa Hoffmann Rosane Silva Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antivirals International Journal of Infectious Diseases Hepatitis C Massively parallel sequencing RAVs Treatment response |
| title | Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antivirals |
| title_full | Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antivirals |
| title_fullStr | Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antivirals |
| title_full_unstemmed | Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antivirals |
| title_short | Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antivirals |
| title_sort | frequency distribution of hcv resistance associated variants in infected patients treated with direct acting antivirals |
| topic | Hepatitis C Massively parallel sequencing RAVs Treatment response |
| url | http://www.sciencedirect.com/science/article/pii/S1201971221012170 |
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