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

Alba Llibre, Yusuke Shimakawa, Estelle Mottez, Shaun Ainsworth, Tan-Phuc Buivan, Rick Firth, Elliott Harrison, Arielle R Rosenberg, Jean-François Meritet, Arnaud Fontanet, Pablo Castan, Antonio Madejón, Mark Laverick, Allison Glass, Raquel Viana, Stanislas Pol, C Patrick McClure, William Lucien Irving, Gino Miele, Matthew L Albert, Darragh Duffy, Alba Llibre, Yusuke Shimakawa, Estelle Mottez, Shaun Ainsworth, Tan-Phuc Buivan, Rick Firth, Elliott Harrison, Arielle R Rosenberg, Jean-François Meritet, Arnaud Fontanet, Pablo Castan, Antonio Madejón, Mark Laverick, Allison Glass, Raquel Viana, Stanislas Pol, C Patrick McClure, William Lucien Irving, Gino Miele, Matthew L Albert, Darragh Duffy

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.

Trial registration number: NCT02992184 .

Keywords: Chronic Viral Hepatitis; Diagnostic Virology; Hepatitis C.

Conflict of interest statement

Competing interests: SA, RF, EH, ML and GM are full time employees of genedrive plc. The remaining authors declare that they have nothing to disclose regarding funding or conflict of interest with respect to this manuscript.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Flow chart of the study participants.
Figure 2
Figure 2
Comparison between the HCV/IPC peak ratio (Genedrive) and HCV RNA levels (Abbott RealTime). (A) Correlation between the HCV/IPC peak ratio and the viral load measured by Abbott RealTime in the Paris cohort (derivation set). (B) Correlation between the viral load estimated by Genedrive and viral load measured by Abbott RealTime in Nottingham cohort (validation set). (C) Agreement between the viral loads estimated by Genedrive and viral loads observed by Abbott RealTime in Nottingham cohort (validation set).

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