Browsing by Author "Little, Susan"

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    Infection staging and incidence surveillance applications of high dynamic range diagnostic immuno-assay platforms
    (Wolters Kluwer, 2017-12) Grebe, Eduard; Welte, Alex; Hall, Jake; Keating, Sheila; Facente, Shelley; Marson, Kara; Martin, Jeffrey; Little, Susan; Price, Matthew; Kallas, Esper; Busch, Michael; Pilcher, Christopher; Murphy, Gary; Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA); South African Centre for Epidemiological Modelling and Analysis (SACEMA)
    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), contextspecific 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 MDRIz 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.