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Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral based treatment regimens: evidence from a global dataset
J Viral Hepat. 2022 Mar 12. doi: 10.1111/jvh.13672. Online ahead of print.
Jake R Morgan1, Elizabeth Marsh2, Alexandra Savinkina2, Sonjelle Shilton3, Shaun Shadaker4, Tengiz Tsertsvadze5, George Kamkamidze6, Maia Alkhazashvili7, Tim Morgan8, Pam Belperio8, L Backus8, Waheed Doss9, Gamal Esmat9, Mohamed Hassany9, Aisha Elsharkawy9, Wafaa Elakel9, Mai Mehrez9, Graham R Foster10, Kinge Wose11, Kara W Chew12, Charles S Chasela13, Ian M Sanne14, Yin M Thanung15, Anne Loarec16, Khawar Aslam17, Suna Balkan18, Philippa J Easterbrook19, Benjamin P Linas220
Department of Health Law, Policy, and Management, Boston University School of Public Health, Boston, MA, United States of America.
Department of Medicine, Section of Infectious Diseases, Boston Medical Center, Boston, MA, United States of America.
Foundation for Innovative New Diagnostics, Geneva, Switzerland.
Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, CDC, Atlanta, United States of America.
Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi, Georgia.
Health Research Union/Clinic NEOLAB, Tbilisi, Georgia.
National Center for Disease Control and Public Health, Tbilisi, Georgia.
Department of Veteran's Affairs, Long Beach, United States of America.
National Committee for Control of Viral Hepatitis NCCVH, Egypt.
Barts Liver Centre, Blizard Institute, QMUL, London, United Kingdom.
Implementation Science Unit, Right to Care, Centurion, South Africa.
Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America.
Implementation Science Unit, Right to Care, Centurion. South Africa, Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Right to Care, Centurion. South Africa, Clinical HIV Research Unit, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand. Johannesburg, South Africa.
Community Partners International, Yangon, Myanmar.
Médecins Sans Frontières, Mozambique.
Médecins Sans Frontières, Karachi, Pakistan.
Médecins Sans Frontières, Paris, France.
Department of Global HIV, Hepatitis and STI Programmes, World Health Organization, Geneva, Switzerland.
Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States of America.
Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12-weeks post-treatment (SVR12). We assembled a global dataset of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique), and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th , 95th, 97th, and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5,973 cases of detectable viremia at SVR12 from the combined dataset. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viremia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR=1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.