Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus

Objective: Recently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucl...

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Main Authors: Llibre, Alba, Shimakawa, Yusuke, Mottez, Estelle, Ainsworth, Shaun, Buivan, Tan-Phuc, Firth, Rick, Harrison, Elliott, Rosenberg, Arielle R., Meritet, Jean-Francois, Fontanet, Arnaud, Castan, Pablo, Madejon, Antonio, Laverick, Mark, Glass, Allison, Viana, Raquel, Pol, Stanislas, McClure, C. Patrick, Irving, William Lucien, Miele, Gino, Albert, Matthew L., Duffy, Darragh
Format: Article
Language:English
Published: BMJ Publishing Group 2018
Online Access:https://eprints.nottingham.ac.uk/51091/
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author Llibre, Alba
Shimakawa, Yusuke
Mottez, Estelle
Ainsworth, Shaun
Buivan, Tan-Phuc
Firth, Rick
Harrison, Elliott
Rosenberg, Arielle R.
Meritet, Jean-Francois
Fontanet, Arnaud
Castan, Pablo
Madejon, Antonio
Laverick, Mark
Glass, Allison
Viana, Raquel
Pol, Stanislas
McClure, C. Patrick
Irving, William Lucien
Miele, Gino
Albert, Matthew L.
Duffy, Darragh
author_facet Llibre, Alba
Shimakawa, Yusuke
Mottez, Estelle
Ainsworth, Shaun
Buivan, Tan-Phuc
Firth, Rick
Harrison, Elliott
Rosenberg, Arielle R.
Meritet, Jean-Francois
Fontanet, Arnaud
Castan, Pablo
Madejon, Antonio
Laverick, Mark
Glass, Allison
Viana, Raquel
Pol, Stanislas
McClure, C. Patrick
Irving, William Lucien
Miele, Gino
Albert, Matthew L.
Duffy, Darragh
author_sort Llibre, Alba
building Nottingham Research Data Repository
collection Online Access
description Objective: Recently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucleic acid testing remains limited. The aim of this study was to develop and validate a point-of-care (PoC) assay for the qualitative detection of HCV RNA. Design: We developed a PoC assay for the qualitative detection of HCV RNA on the PCR Genedrive instrument. We validated the Genedrive HCV assay through a case–control study comparing results with those obtained with the Abbott RealTime HCV test. Results: The PoC assay identified all major HCV genotypes, with a limit of detection of 2362 IU/mL (95% CI 1966 to 2788). Using 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA, the Genedrive HCV assay showed 98.6% sensitivity (95% CI 96.9% to 99.5%) and 100% specificity (95% CI 99.3% to 100%) to detect HCV. In addition, melting peak ratiometric analysis demonstrated proof-of-principle for semiquantification of HCV. The test was further validated in a real clinical setting in a resource-limited country. Conclusion: We report a rapid, simple, portable and accurate PoC molecular test for HCV, with sensitivity and specificity that fulfils the recent FIND/WHO Target Product Profile for HCV decentralised testing in low-income and middle-income countries. This Genedrive HCV assay may positively impact the continuum of HCV care from screening to cure by supporting real-time treatment decisions.
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spelling nottingham-510912018-04-11T13:21:47Z https://eprints.nottingham.ac.uk/51091/ Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus Llibre, Alba Shimakawa, Yusuke Mottez, Estelle Ainsworth, Shaun Buivan, Tan-Phuc Firth, Rick Harrison, Elliott Rosenberg, Arielle R. Meritet, Jean-Francois Fontanet, Arnaud Castan, Pablo Madejon, Antonio Laverick, Mark Glass, Allison Viana, Raquel Pol, Stanislas McClure, C. Patrick Irving, William Lucien Miele, Gino Albert, Matthew L. Duffy, Darragh Objective: Recently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucleic acid testing remains limited. The aim of this study was to develop and validate a point-of-care (PoC) assay for the qualitative detection of HCV RNA. Design: We developed a PoC assay for the qualitative detection of HCV RNA on the PCR Genedrive instrument. We validated the Genedrive HCV assay through a case–control study comparing results with those obtained with the Abbott RealTime HCV test. Results: The PoC assay identified all major HCV genotypes, with a limit of detection of 2362 IU/mL (95% CI 1966 to 2788). Using 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA, the Genedrive HCV assay showed 98.6% sensitivity (95% CI 96.9% to 99.5%) and 100% specificity (95% CI 99.3% to 100%) to detect HCV. In addition, melting peak ratiometric analysis demonstrated proof-of-principle for semiquantification of HCV. The test was further validated in a real clinical setting in a resource-limited country. Conclusion: We report a rapid, simple, portable and accurate PoC molecular test for HCV, with sensitivity and specificity that fulfils the recent FIND/WHO Target Product Profile for HCV decentralised testing in low-income and middle-income countries. This Genedrive HCV assay may positively impact the continuum of HCV care from screening to cure by supporting real-time treatment decisions. BMJ Publishing Group 2018-04-03 Article PeerReviewed application/pdf en cc_by_nc https://eprints.nottingham.ac.uk/51091/1/gutjnl-2017-315783.pdf Llibre, Alba, Shimakawa, Yusuke, Mottez, Estelle, Ainsworth, Shaun, Buivan, Tan-Phuc, Firth, Rick, Harrison, Elliott, Rosenberg, Arielle R., Meritet, Jean-Francois, Fontanet, Arnaud, Castan, Pablo, Madejon, Antonio, Laverick, Mark, Glass, Allison, Viana, Raquel, Pol, Stanislas, McClure, C. Patrick, Irving, William Lucien, Miele, Gino, Albert, Matthew L. and Duffy, Darragh (2018) Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus. Gut . ISSN 1468-3288 http://gut.bmj.com/content/early/2018/04/03/gutjnl-2017-315783 doi:10.1136/gutjnl-2017-315783 doi:10.1136/gutjnl-2017-315783
spellingShingle Llibre, Alba
Shimakawa, Yusuke
Mottez, Estelle
Ainsworth, Shaun
Buivan, Tan-Phuc
Firth, Rick
Harrison, Elliott
Rosenberg, Arielle R.
Meritet, Jean-Francois
Fontanet, Arnaud
Castan, Pablo
Madejon, Antonio
Laverick, Mark
Glass, Allison
Viana, Raquel
Pol, Stanislas
McClure, C. Patrick
Irving, William Lucien
Miele, Gino
Albert, Matthew L.
Duffy, Darragh
Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus
title Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus
title_full Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus
title_fullStr Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus
title_full_unstemmed Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus
title_short Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus
title_sort development and clinical validation of the genedrive point-of-care test for qualitative detection of hepatitis c virus
url https://eprints.nottingham.ac.uk/51091/
https://eprints.nottingham.ac.uk/51091/
https://eprints.nottingham.ac.uk/51091/