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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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
Issue number5
Publication statusPublished - 2017

Bibliographical note

Funding Information:
All authors, as members or collaborators of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA), were supported by grants from the Bill and Melinda Gates Foundation (OPP1017716, OPP1062806 and OPP1115799). Additional support for analysis was provided by a grant from the US National Institutes of Health (R34 MH096606), and specimen and data collection were funded in part by additional grants from the NIH (P01 AI071713, R01 HD074511, P30 AI027763, R24 AI067039, U01 AI043638, P01 AI074621, and R24 AI106039); California HIV-1 Research Program (RN07-SD-702); Brazilian Program for STD and AIDS, Ministry of Health (914/BRA/3014-UNESCO); and São Paulo City Health Department (2004-0.168.922–7). S.M.K and M.P.B. receive ongoing grant support from Abbott, Ortho Clinical Diagnostics, and Sedia Biosciences Corporation for the evaluation of their respective assays. M.A.P. and selected samples from IAVI-supported cohorts are funded by IAVI with the generous support of USAID and other donors; a full list of IAVI donors is available at

Publisher Copyright:
Copyright © 2017 The Author(s).


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


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