Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir Treatment
Direct-acting antivirals (DAAs) have revolutionised the treatment of Hepatitis C virus (HCV), allowing the World Health Organisation (WHO) to set a target of eliminating HCV by 2030. In this study we aimed to investigate glecaprevir and pibrentasvir (GP) treatment outcomes in a cohort of patients wi...
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MDPI AG
2022-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/8/1678 |
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| author | Rajiv Shah Stephen T. Barclay Erica S. Peters Ray Fox Rory Gunson Amanda Bradley-Stewart Samantha J. Shepherd Alasdair MacLean Lily Tong Vera Jannie Elisabeth van Vliet Michael Ngan Chiu Bong Ana Filipe Emma C. Thomson Chris Davis |
| author_facet | Rajiv Shah Stephen T. Barclay Erica S. Peters Ray Fox Rory Gunson Amanda Bradley-Stewart Samantha J. Shepherd Alasdair MacLean Lily Tong Vera Jannie Elisabeth van Vliet Michael Ngan Chiu Bong Ana Filipe Emma C. Thomson Chris Davis |
| author_sort | Rajiv Shah |
| collection | DOAJ |
| description | Direct-acting antivirals (DAAs) have revolutionised the treatment of Hepatitis C virus (HCV), allowing the World Health Organisation (WHO) to set a target of eliminating HCV by 2030. In this study we aimed to investigate glecaprevir and pibrentasvir (GP) treatment outcomes in a cohort of patients with genotype 2a infection. Methods: Clinical data and plasma samples were collected in NHS Greater Glasgow & Clyde. Next generation whole genome sequencing and replicon assays were carried out at the MRC-University of Glasgow Centre for Virus Research. Results: 132 cases infected with genotype 2a HCV were identified. The SVR rate for this group was 91% (112/123) following treatment with GP. An NS5A polymorphism, L31M, was detected in all cases of g2a infection, and L31M+R353K in individuals that failed treatment. The results showed that R353K was present in 90% of individuals in the Glasgow genotype 2a phylogenetic cluster but in less than 5% of all HCV subtype 2a published sequences. In vitro efficacy of pibrentasvir against sub-genomic replicon constructs containing these mutations showed a 2-fold increase in IC<sub>50</sub> compared to wildtype. Conclusion: This study describes a cluster of HCV genotype 2a infection associated with a lower-than-expected SVR rate following GP treatment in association with the NS5A mutations L31M+R353K. |
| first_indexed | 2024-03-09T12:23:01Z |
| format | Article |
| id | doaj.art-a5ce3c72db0e4d45a508029127e6c355 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T12:23:01Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a5ce3c72db0e4d45a508029127e6c3552023-11-30T22:38:47ZengMDPI AGViruses1999-49152022-07-01148167810.3390/v14081678Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir TreatmentRajiv Shah0Stephen T. Barclay1Erica S. Peters2Ray Fox3Rory Gunson4Amanda Bradley-Stewart5Samantha J. Shepherd6Alasdair MacLean7Lily Tong8Vera Jannie Elisabeth van Vliet9Michael Ngan Chiu Bong10Ana Filipe11Emma C. Thomson12Chris Davis13Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKNHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UKNHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UKNHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UKThomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKNHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UKNHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UKNHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UKThomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKThomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKThomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKThomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKThomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKThomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKDirect-acting antivirals (DAAs) have revolutionised the treatment of Hepatitis C virus (HCV), allowing the World Health Organisation (WHO) to set a target of eliminating HCV by 2030. In this study we aimed to investigate glecaprevir and pibrentasvir (GP) treatment outcomes in a cohort of patients with genotype 2a infection. Methods: Clinical data and plasma samples were collected in NHS Greater Glasgow & Clyde. Next generation whole genome sequencing and replicon assays were carried out at the MRC-University of Glasgow Centre for Virus Research. Results: 132 cases infected with genotype 2a HCV were identified. The SVR rate for this group was 91% (112/123) following treatment with GP. An NS5A polymorphism, L31M, was detected in all cases of g2a infection, and L31M+R353K in individuals that failed treatment. The results showed that R353K was present in 90% of individuals in the Glasgow genotype 2a phylogenetic cluster but in less than 5% of all HCV subtype 2a published sequences. In vitro efficacy of pibrentasvir against sub-genomic replicon constructs containing these mutations showed a 2-fold increase in IC<sub>50</sub> compared to wildtype. Conclusion: This study describes a cluster of HCV genotype 2a infection associated with a lower-than-expected SVR rate following GP treatment in association with the NS5A mutations L31M+R353K.https://www.mdpi.com/1999-4915/14/8/1678hepatitis C virusdirect-acting antiviralsglecaprevirpibrentasvirsustained virological responseresistance associated substitutions |
| spellingShingle | Rajiv Shah Stephen T. Barclay Erica S. Peters Ray Fox Rory Gunson Amanda Bradley-Stewart Samantha J. Shepherd Alasdair MacLean Lily Tong Vera Jannie Elisabeth van Vliet Michael Ngan Chiu Bong Ana Filipe Emma C. Thomson Chris Davis Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir Treatment Viruses hepatitis C virus direct-acting antivirals glecaprevir pibrentasvir sustained virological response resistance associated substitutions |
| title | Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir Treatment |
| title_full | Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir Treatment |
| title_fullStr | Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir Treatment |
| title_full_unstemmed | Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir Treatment |
| title_short | Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir Treatment |
| title_sort | characterisation of a hepatitis c virus subtype 2a cluster in scottish pwid with a suboptimal response to glecaprevir pibrentasvir treatment |
| topic | hepatitis C virus direct-acting antivirals glecaprevir pibrentasvir sustained virological response resistance associated substitutions |
| url | https://www.mdpi.com/1999-4915/14/8/1678 |
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