François M J Lamoury1, Angelica Soker1, Danica Martinez1, Behzad Hajarizadeh1, Evan B Cunningham1, Philip Cunningham2, Philip Bruggmann3, Graham R Foster4, Olav Dalgard5, Markus Backmund6, Brian Conway7, Geert Robaeys8, Tracy Swan9, Gavin Cloherty10, Pip Marks1, Jason Grebely1, Gregory J Dore1, Tanya L Applegate11. 1. The Kirby Institute, UNSW Sydney, Sydney, Australia. 2. St. Vincent's Applied Medical Research, Darlinghurst, Sydney, Australia. 3. Arud Centres for Addiction Medicine, Zurich, Switzerland. 4. Queen Mary University of London, Institute of Cell and Molecular Science, London, UK. 5. Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 6. Department of Addiction Medicine, Munich-Schwabing Hospital, Munich, Germany. 7. Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada. 8. Department of Gastroenterology and Hepatology, Ziekenhuis Oost-Limburg, Schiepse, Belgium; Faculty of Medicine and Life Sciences, Limburg Clinical Research Program, Belgium; Department of Hepatology UZ Leuven, Leuven, Belgium. 9. Department of Gastroenterology and Hepatology, Ziekenhuis Oost-Limburg, Schiepse, Belgium. 10. Abbott Diagnostics, Abbott Park, IL, USA. 11. The Kirby Institute, UNSW Sydney, Sydney, Australia. Electronic address: t.applegate@kirby.unsw.edu.au.
Abstract
BACKGROUND: Simple, affordable diagnostic tools are essential to facilitate global hepatitis C virus (HCV) elimination efforts. OBJECTIVES: This study evaluated the clinical performance of core antigen (HCVcAg) assay from plasma samples to monitor HCV treatment efficacy and HCV viral recurrence. STUDY DESIGN: Plasma samples from a study of response-guided pegylated-interferon/ribavirin therapy for people who inject drugs with chronic HCV genotype 2/3 infection were assessed for HCV RNA (AmpliPrep/COBAS Taqman assay, Roche) and HCVcAg (ARCHITECT HCV Ag, Abbott Diagnostics) during and after therapy. The sensitivity and specificity of the HCVcAg assay was compared to the HCV RNA assay (gold standard). RESULTS: A total of 335 samples from 92 enrolled participants were assessed (mean 4 time-points per participant). At baseline, end of treatment response (ETR) and sustained virological response (SVR) visits, the sensitivity of the HCVcAg assay with quantifiable HCV RNA threshold was 94% (95% CI: 88%, 98%), 56% (21%, 86%) and 100%, respectively. The specificity was between 98 to 100% for all time-points assessed. HCVcAg accurately detected all six participants with viral recurrence, demonstrating 100% sensitivity and specificity. One participant with detectable (non-quantifiable) HCV RNA and non-reactive HCVcAg at SVR12 subsequently cleared HCV RNA at SVR24. CONCLUSIONS: HCVcAg demonstrated high sensitivity and specificity for detection of pre-treatment and post-treatment viraemia. This study indicates that confirmation of active HCV infection, including recurrent viraemia, by HCVcAg is possible. Reduced on-treatment sensitivity of HCVcAg may be a clinical advantage given the moves toward simplification of monitoring schedules.
BACKGROUND: Simple, affordable diagnostic tools are essential to facilitate global hepatitis C virus (HCV) elimination efforts. OBJECTIVES: This study evaluated the clinical performance of core antigen (HCVcAg) assay from plasma samples to monitor HCV treatment efficacy and HCV viral recurrence. STUDY DESIGN: Plasma samples from a study of response-guided pegylated-interferon/ribavirin therapy for people who inject drugs with chronic HCV genotype 2/3 infection were assessed for HCV RNA (AmpliPrep/COBAS Taqman assay, Roche) and HCVcAg (ARCHITECT HCV Ag, Abbott Diagnostics) during and after therapy. The sensitivity and specificity of the HCVcAg assay was compared to the HCV RNA assay (gold standard). RESULTS: A total of 335 samples from 92 enrolled participants were assessed (mean 4 time-points per participant). At baseline, end of treatment response (ETR) and sustained virological response (SVR) visits, the sensitivity of the HCVcAg assay with quantifiable HCV RNA threshold was 94% (95% CI: 88%, 98%), 56% (21%, 86%) and 100%, respectively. The specificity was between 98 to 100% for all time-points assessed. HCVcAg accurately detected all six participants with viral recurrence, demonstrating 100% sensitivity and specificity. One participant with detectable (non-quantifiable) HCV RNA and non-reactive HCVcAg at SVR12 subsequently cleared HCV RNA at SVR24. CONCLUSIONS:HCVcAg demonstrated high sensitivity and specificity for detection of pre-treatment and post-treatment viraemia. This study indicates that confirmation of active HCV infection, including recurrent viraemia, by HCVcAg is possible. Reduced on-treatment sensitivity of HCVcAg may be a clinical advantage given the moves toward simplification of monitoring schedules.
Authors: Jason Grebely; Julie Bruneau; Jeffrey V Lazarus; Olav Dalgard; Philip Bruggmann; Carla Treloar; Matthew Hickman; Margaret Hellard; Teri Roberts; Levinia Crooks; Håvard Midgard; Sarah Larney; Louisa Degenhardt; Hannu Alho; Jude Byrne; John F Dillon; Jordan J Feld; Graham Foster; David Goldberg; Andrew R Lloyd; Jens Reimer; Geert Robaeys; Marta Torrens; Nat Wright; Icro Maremmani; Brianna L Norton; Alain H Litwin; Gregory J Dore Journal: Int J Drug Policy Date: 2017-07-03