title: Use of Hepatitis C Virus (HCV) Immunoglobulin G Antibody Avidity as a Biomarker to Estimate the Population-Level Incidence of HCV Infection.
abstract: BACKGROUND
  Sensitive methods are needed to estimate the population-level incidence of hepatitis C virus (HCV) infection.
  
  
  METHODS
  We developed an HCV immunoglobulin G (IgG) antibody avidity assay by modifying the Ortho 3.0 HCV enzyme-linked immunoassay and tested 997 serum or plasma samples from 568 people who inject drugs enrolled in prospective cohort studies. Avidity-based testing algorithms were evaluated by their (1) mean duration of recent infection (MDRI), defined as the average time an individual is identified as having been recently infected, according to a given algorithm; (2) false-recent rate, defined as the proportion of samples collected >2 years after HCV seroconversion that were misclassified as recent; (3) sample sizes needed to estimate incidence; and (4) power to detect a reduction in incidence between serial cross-sectional surveys.
  
  
  RESULTS
  A multiassay algorithm (defined as an avidity index of <30%, followed by HCV viremia detection) had an MDRI of 147 days (95% confidence interval [CI], 125-195 days), and the false-recent rates were 0.7% (95% CI, .2%-1.8%) and 7.6% (95% CI, 4.2%-12.3%) among human immunodeficiency virus (HIV)-negative and HIV-positive persons, respectively. In various simulated high-risk populations, this algorithm required <1000 individuals to estimate incidence (relative standard error, 30%) and had >80% power to detect a 50% reduction in incidence.
  
  
  CONCLUSIONS
  Avidity-based algorithms have the capacity to accurately estimate HCV infection incidence and rapidly assess the impact of public health efforts among high-risk populations. Efforts to optimize this method should be prioritized.
authors.affiliation: Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Eshan U
authors.initials: EU
authors.lastname: Patel
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Cox
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Shruti H
authors.initials: SH
authors.lastname: Mehta
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Denali
authors.initials: D
authors.lastname: Boon
authors.affiliation: Department of Medicine, New York Medical College, New York.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Mullis
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Jacquie
authors.initials: J
authors.lastname: Astemborski
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine.
authors.forename: William O
authors.initials: WO
authors.lastname: Osburn
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Quinn
authors.affiliation: Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health Department of Medicine, Johns Hopkins University School of Medicine.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redd
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: David L
authors.initials: DL
authors.lastname: Thomas
authors.affiliation: Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health Department of Medicine, Johns Hopkins University School of Medicine Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.affiliation: Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health Department of Medicine, Johns Hopkins University School of Medicine Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000915:Antibody Affinity; D015415:Biomarkers / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018937:Hepatitis C Antibodies; D007074:Immunoglobulin G
keywords: HCV; HIV; antibody response; incidence testing; people who inject drugs; recent infection; surveillance