Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms

J Acquir Immune Defic Syndr. 2017 Dec 15;76(5):547-555. doi: 10.1097/QAI.0000000000001537.


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 ≈ 0.5% and 1.5%, respectively at MDRI ≈ 200 days), and the unmodified diagnostic ARCHITECT produces incidence estimates with comparable precision to LAg (relative SE ≈ 17.5% and 15%, respectively at MDRI ≈ 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diagnostic Tests, Routine
  • HIV Antibodies / analysis
  • HIV Antigens / analysis
  • HIV Infections / epidemiology*
  • HIV-1 / classification
  • Humans
  • Immunoassay / methods*
  • Incidence
  • Population Surveillance*
  • Sensitivity and Specificity
  • Time Factors


  • HIV Antibodies
  • HIV Antigens