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Original article
Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus
  1. Alba Llibre1,2,
  2. Yusuke Shimakawa3,
  3. Estelle Mottez4,5,
  4. Shaun Ainsworth6,
  5. Tan-Phuc Buivan4,5,
  6. Rick Firth6,
  7. Elliott Harrison6,
  8. Arielle R Rosenberg7,
  9. Jean-François Meritet7,
  10. Arnaud Fontanet3,8,
  11. Pablo Castan9,
  12. Antonio Madejón10,
  13. Mark Laverick6,
  14. Allison Glass11,
  15. Raquel Viana11,
  16. Stanislas Pol1,2,4,12,
  17. C Patrick McClure13,
  18. William Lucien Irving13,
  19. Gino Miele6,
  20. Matthew L Albert1,2,4,14,
  21. Darragh Duffy1,2,4
  1. 1 Immunobiology of Dendritic Cells, Institut Pasteur, Paris, France
  2. 2 Inserm U1223, Institut Pasteur, Paris, France
  3. 3 Unité d’Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France
  4. 4 Centre for Translational Research, Institut Pasteur, Paris, France
  5. 5 INSERM UMS20, Institut Pasteur, Paris, France
  6. 6 genedrive pIc, Manchester, UK
  7. 7 Université Paris Descartes, EA4474 "Hepatitis C Virology", AP-HP, Hôpital Cochin, Service de Virologie, Paris, France
  8. 8 PACRI Unit, Conservatoire National des Arts et Métiers, Paris, France
  9. 9 Hospital Universitario La Paz, Madrid, Spain
  10. 10 Liver Unit, Hospital Universitario La Paz, CIBERehd, IdiPAZ, Madrid, Spain
  11. 11 Lancet Laboratories, Johannesburg, South Africa
  12. 12 Université Paris Descartes, EA4474 "Hepatitis C Virology", AP-HP, Hôpital Cochin, Service de Virologie, Paris, France
  13. 13 Gastrointestinal and Liver Disorders Theme, NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
  14. 14 Department of Cancer Immunology, Genentech Inc, San Francisco, California, USA
  1. Correspondence to Dr Gino Miele, genedrive plc, Manchester, UK; g.miele{at}genedrive.com and Darragh Duffy, Immunobiology of Dendritic Cells, Institut Pasteur, Paris 75015, France; darragh.duffy{at}pasteur.fr

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.

  • Diagnostic Virology
  • Chronic Viral Hepatitis
  • Hepatitis C

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • MLA and DD contributed equally.

  • AL and YS contributed equally.

  • Contributors AL, T-PB, ARR, J-FM, PC, AM, CPM, WLI, AG and RV analysed clinical samples. AL, YS and SA analysed the data. SA, RF, EH, ML and GM developed the assay. YS, EM, AF, SP, GM, MLA and DD designed the study. AF, SP, GM, MLA and DD secured funding. AL, YS and DD wrote the manuscript. All authors approved the final version and revised it critically before submission.

  • Funding The overall study was funded by the European Commission FP7 (n° 601851). Work performed in Nottingham and South Africa received additional financial support from genedrive plc.

  • 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.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval CPP IDF VI (Paris, France)

  • Provenance and peer review Not commissioned; externally peer reviewed.

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