Infection staging and incidence surveillance applications of high dynamic range diagnostic immuno-assay platforms

Eduard Grebe, Alex Welte, Jake Hall, Sheila M. Keating, Shelley N. Facente, Kara Marson, Jeffrey N. Martin, Susan J. Little, Matthew A. Price, Esper G. Kallas, Michael P. Busch, Christopher D. Pilcher, Gary Murphy

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Background: Custom HIV staging assays, including the Sedia HIV-1 Limiting Antigen (LAg) Avidity EIA and avidity modifications of the Ortho VITROS anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify "recent" infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and long-standing infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications. Methods: We tested a panel of 2500 well-characterized specimens with estimable duration of HIV infection with the 3 assays and the unmodified ARCHITECT. Regression models were used to estimate mean durations of recent infection (MDRIs), context-specific false-recent rates (FRRs) and correlation between diagnostic signal intensity and LAg measurements. Hypothetical epidemiological scenarios were constructed to evaluate utility in surveillance applications. Results: Over a range of MDRIs (reflecting recency discrimination thresholds), a diluted ARCHITECT-based RITA produced lower FRRs than the VITROS platform (FRR z 0.5% and 1.5%, respectively at MDRI z 200 days), and the unmodified diagnostic ARCHITECT produces incidence estimates with comparable precision to LAg (relative SE z 17.5% and 15%, respectively at MDRI z 200 days). ARCHITECT S/CO measurements were highly correlated with LAg optical density measurements (r = 0.80), and values below 200 are strongly predictive of LAg recency and duration of infection less than 1 year. Conclusions: Low quantitative measurements from the unmodified ARCHITECT obviate the need for additional recency testing, and its use is feasible in clinical staging and incidence surveillance applications.

Original languageEnglish
Pages (from-to)547-555
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume76
Issue number5
DOIs
Publication statusPublished - 2017

Keywords

  • Diagnostic assays
  • Incidence
  • Infection staging
  • Infection timing
  • Recent infection
  • Staging assays

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