Frequency distribution of HCV resistance-associated variants in infected patients treated with direct-acting antivirals

•Resistance-associated variants (RAVs) were evaluated by massively parallel sequencing.•Non-synonymous substitutions were detected for genotypes 1 and 3 at baseline.•Higher non-synonymous substitutions were found in hepatitis C virus (HCV) 3a NS3/NS5a regions.•RAVs were found in responders and non-r...

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Published in:	International journal of infectious diseases Vol. 115; pp. 171 - 177
Main Authors:	Cabral, Bianca Catarina Azeredo, Ramos, Juliene Antonio, Silveira, Amanda Laryssa de Melo, Nascimento, Érica Ramos dos Santos, Ferreira, Selma Baía, Coelho, Henrique Sérgio Moraes, Moura-Neto, Rodrigo Soares, Villela-Nogueira, Cristiane Alves, Hoffmann, Luísa, Silva, Rosane
Format:	Journal Article
Language:	English
Published:	Canada Elsevier Ltd 01-02-2022 Elsevier
Subjects:	Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Drug Resistance, Viral - genetics Genotype Hepacivirus - genetics Hepatitis C Hepatitis C - drug therapy Hepatitis C, Chronic - drug therapy Humans Massively parallel sequencing Persistent Infection RAVs Treatment response Viral Nonstructural Proteins - genetics Massively parallel sequencing RAVs Treatment response Hepatitis C
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Summary:	•Resistance-associated variants (RAVs) were evaluated by massively parallel sequencing.•Non-synonymous substitutions were detected for genotypes 1 and 3 at baseline.•Higher non-synonymous substitutions were found in hepatitis C virus (HCV) 3a NS3/NS5a regions.•RAVs were found in responders and non-responders.•RAVs at baseline did not interfere with the success of direct-acting antiviral therapy. 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. 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1201-9712 1878-3511
DOI:	10.1016/j.ijid.2021.12.320