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

Alba Llibre (1) , Yusuke Shimakawa (2) , Estelle Mottez (3) , Shaun Ainsworth (4) , Tan-Phuc Buivan (3) , Rick Firth (4) , Elliott Harrison (4) , Arielle R. Rosenberg (5) , Jean-François Meritet (5) , Arnaud Fontanet (2, 6) , Pablo Castan (7) , Antonio Madejón (8, 7) , Mark Laverick (4) , Allison Glass (9) , Raquel Viana (9) , Stanislas Pol (3, 1, 5) , C Patrick Mcclure (10) , William Lucien Irving (10) , Gino Miele (4) , Matthew Albert (1, 3, 11) , Darragh Duffy (1, 3)

1 Immunobiologie des Cellules dendritiques
2 Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology
3 CRT - Centre de Recherche Translationnelle - Center for Translational Science
4 Genedrive plc [Manchester]
5 EA 4474 - Virologie de l'hépatite C
6 PACRI - Pasteur-Cnam Risques infectieux et émergents
7 Hospital Universitario La Paz
8 CIBERehd - Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas
9 Lancet Laboratories [Afrique du sud]
10 UON - University of Nottingham, UK
11 Genentech, Inc. [San Francisco]

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.

Mots clés: Chronic Viral Hepatitis; Diagnostic Virology; Hepatitis C

Domaines: Immunologie

Alba Llibre, Yusuke Shimakawa, Estelle Mottez, Shaun Ainsworth, Tan-Phuc Buivan, et al.. Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus. Gut, 2018, 11, pp.1-8. ⟨10.1136/gutjnl-2017-315783⟩. ⟨pasteur-01769953⟩