Establishment of an anti-hepatitis C virus IgG avidity test for dried serum/plasma spots

J Immunol Methods. 2020 Apr:479:112744. doi: 10.1016/j.jim.2020.112744. Epub 2020 Jan 17.

Abstract

Monitoring recency of infection helps to identify current transmission in vulnerable populations for effective disease control. We have established an in-house avidity based hepatitis C virus (HCV) recency assay based on the Monolisa Anti-HCV PLUS Version 3 ELISA kit for use of dried serum/plasma spots (DS/PS) in order to distinguish recent and long-term infections. A first panel of DS/PS (n = 218; genotype 1 n = 170 and non-genotype 1 n = 48) consisting of primary and at least one follow up sample was used to analyze the temporal changes of the Avidity Index (AI) over time. Sub-panels of longitudinal DS/PS (n = 66) and acute cases (<26 weeks; n = 34) were taken to calculate the Mean Duration of Recent Infection (MDRI) and the False Long-term Rate (FLTR), respectively. A second panel of DS/PS >104 weeks (n = 132) and a third panel of DS/PS prepared from resolved infections (≥180 days since last positive; n = 32) were used to calculate the False Recent Rate (FRR). For all genotypes, the optimal AI cut-off was determined to be 40% resulting in an MDRI of 364 days (95% CI: 223-485). FLTR was 5.9% (95% CI: 0.7-19.7), 8.3% (95% CI: 1-27), and 0% (-) and FRR was 13.6% (95% CI: 8.3-20.7), 11.7% (95% CI: 6.6-19), and 30.6% (95% CI: 9.1-61.4) for all genotypes, genotype 1, and non-genotype 1 infections, respectively. For resolved infections, the FRR was 53.1% (95% CI: 35.8-70.4). Thus, this assay performs particularly well for genotype 1 reaching a high rate of correct discriminations between infections acquired less than a year before diagnosis and those acquired earlier by applying an AI cut-off of 40%. Due to a rapid decline in avidity post resolution of an HCV infection this assay is not recommended to be used in HCV RNA negative patients.

Keywords: Avidity assay; Dried serum/plasma spot; HCV; Recent infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Affinity
  • Cohort Studies
  • Dried Blood Spot Testing / methods*
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Female
  • Follow-Up Studies
  • Genotype*
  • Germany
  • Hepacivirus / physiology*
  • Hepatitis C / immunology*
  • Hepatitis C Antibodies / metabolism*
  • Humans
  • Immunoglobulin G / metabolism*
  • Male
  • Middle Aged
  • Reference Standards
  • Sensitivity and Specificity

Substances

  • Hepatitis C Antibodies
  • Immunoglobulin G