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

Abstract

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.

Citation

Llibre, A., Shimakawa, Y., Mottez, E., Ainsworth, S., Buivan, T.-P., Firth, R., Harrison, E., Rosenberg, A. R., Meritet, J.-F., Fontanet, A., Castan, P., Madejon, A., Laverick, M., Glass, A., Viana, R., Pol, S., McClure, C. P., Irving, W. L., Miele, G., Albert, M. L., & Duffy, D. (2018). Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus. Gut, 67(11), 2017-2024. https://doi.org/10.1136/gutjnl-2017-315783

• Journal Article Type: Article
• Acceptance Date: Mar 14, 2018
• Online Publication Date: Apr 3, 2018
• Publication Date: 2018-11
• Deposit Date: Apr 11, 2018
• Publicly Available Date: Apr 11, 2018
• Journal: Gut
• Print ISSN: 0017-5749
• Electronic ISSN: 1468-3288
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 67
• Issue: 11
• Pages: 2017-2024
• DOI: https://doi.org/10.1136/gutjnl-2017-315783
• Keywords: Gastroenterology
• Public URL: https://nottingham-repository.worktribe.com/output/923339
• Publisher URL: http://gut.bmj.com/content/early/2018/04/03/gutjnl-2017-315783
• Contract Date: Apr 11, 2018