Exclusion of Hepatitis C Viremia by Early Read of Point-of-Care Antibody Test

Background: To achieve global hepatitis C virus (HCV) elimination, scale-up of testing is required as diagnosis rates remain low. Point-of-care (POC) antibody testing increases access for difficult-to-reach populations, however the current 20-40 minute read time limits utility. We sought to determine whether there was a relationship between time to antibody positivity and presence of viremia. Methods: HCV viremic and non-viremic antibody-positive patients were tested with the OraQuick POC HCV antibody test using whole blood or oral fluid. Results were recorded at 15 second intervals to determine time to positivity. Results were validated in an independent screening cohort of high-risk individuals. Findings: All viremic patients had a positive blood result by 5 minutes. Median time to positivity for 171 viremic patients was 2.6 (1.8-4.6) versus 4.1 minutes (2.3-14.4) for 108 with resolved infection (p<0.001). The 5-minute threshold was confirmed in 176 HCV-antibody-positive individuals in a real-world cohort. Overall, the sensitivity for viremic patients at 5 minutes was 100% (95% CI 98.4-100%) and the negative predictive value was 100% (95% CI 94.9-100%). The positive predictive value at 5 minutes was inadequate to avoid HCV RNA testing 62.0% (95% CI 56.7-67.0%) entirely. Time to positivity was not predictive of viremia in oral fluid. Interpretation: A negative result on the OraQuick antibody test at 5 minutes is adequate to exclude HCV viremia, enabling high throughput screening and reducing the need for reflex HCV RNA testing. Funding Statement: This study was supported by the Viral Hepatitis Care Network (VIRCAN) and 3000 OraQuick HCV antibody kits were received in-kind from OraSure. JVL is supported by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III/ESF, European Union (CP18/00074)). Declaration of Interests: Mia J. Biondi has served as a speaker, a consultant, and/or advisory board member for Gilead, AbbVie, and Specialty Rx; and received research funding from Gilead and AbbVie. David Fletcher has served as an advisory board member for Gilead, AbbVie, and Merck. Hemat Shah has served as a speaker, a consultant and/or an advisory board member for AbbVie, Gilead, Intercept, Lupin, and Merck; and has received research funding from Boehringer-Ingelheim and Gilead. Betttina E. Hansen as served as a speaker, a consultant and/or an advisory board member for Intercept, Cymabay, Albireo, Mirum, ChemomAb, and Calliditas; and has received research funding from Intercept, Cymabay, Albireo and Mirum. Jeffrey V. Lazarus has served as a speaker, a consultant, and/or advisory board member for Gilead and AbbVie; and received research funding from GlaxoSmithKline, Cepheid, and Janssen. Harry L.A. Janssen has served as a speaker, a consultant and/or an advisory board member for Arbutus, Arena, Enyo, Gilead Sciences, GlaxoSmithKline, Janssen, Medimmune, Merck, Roche, Vir-Bio, Viroclinics; and has received research funding from AbbVie, Arbutus, Bristol-Myers Squibb, Gilead Sciences, Janssen, Medimmune, Merck, and Roche. Jordan J. Feld has served as a speaker, a consultant and/or an advisory board member for AbbVie, Enanta, Contravir, Roche, and Abbott; and has received research funding from AbbVie, Gilead, Janssen and Abbott. All other authors declare no conflict of interest. Ethics Approval Statement: All patients provided written informed consent and the protocol was approved by the Research Ethics Board of the University Health Network. The protocol for the Madrid validation cohort was reviewed by El cribado tiene un consentimiento informado y ha pasado el Comite de Etica del Hospital Gregorio Maranon and all individuals provided written informed consent.