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

Abstract

ObjectiveRecently 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.DesignWe 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.ResultsThe 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.ConclusionWe 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 numberNCT02992184.

In‐field evaluation of Xpert® HCV viral load Fingerstick assay in people who inject drugs in Tanzania

“…Currently, two CE-in vitro diagnostic point-of-care platforms (Genedrive ® ) and Xpert ® (Cepheid) for HCV RNA NAT in plasma exist, with one (Xpert ® ) receiving WHO prequalification in 2017. 8,9 However, with the existing point-of-care tests there still remains the issue of plasma separation. Whole blood samples of 50-70 µL have been demonstrated as an alternative method to decentralise and simplify sample collection using dried blood spots (DBS).…”

“…One of the novel solutions to mitigate the dependence on skilled laboratories and personnel is the emergence of simple point‐of‐care tests for HCV RNA. Currently, two CE‐in vitro diagnostic point‐of‐care platforms (Genedrive ® ) and Xpert ® (Cepheid) for HCV RNA NAT in plasma exist, with one (Xpert ® ) receiving WHO prequalification in 2017 …”

Micro‐elimination of hepatitis C virus

“…Patient follow‐up and linkage to care must also be organized because previously diagnosed patients may be lost to follow‐up in the presence of treatment restrictions (prioritization) . This requires new technologies such as RDOT or ‘Point of Care’ tests, which allow a serological diagnosis, and especially detection of positive viraemia within 20‐30 minutes, for a ‘test and treat’ policy . All these measures can help meet the challenge by improving ‘diagnostic burn‐out’, with five times more viral C infections than diagnosed in 2016 and five times fewer cures than new infections …”

What is required from HCV point-of-care tests to reduce the burden of hepatitis C infection? ‘Development and clinical validation of the genedrive point-of-care test for qualitative detection of hepatitis C virus’

“…The work conducted by Llibre et al 3 paves the way for further innovations and strategies for the reduction of the HCV epidemic.…”

“…From a large case–control study including samples from HCV-infected -treatment naïve- and uninfected patients identified in 2 European (France and UK) and 10 African countries, the authors assessed the performance of the new test for the detection of HCV RNA using the Abbott real-time PCR assay as a reference 3. They found high diagnostic sensitivity and specificity of the assay (close to 100%) to detect HCV RNA in Western as well as South-African laboratories with pangenotypic performance.…”