Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms. Grebe, E., Welte, A., Hall, J., Keating, S. M., Facente, S. N., Marson, K., Martin, J. N., Little, S. J., Price, M. A., Kallas, E. G., Busch, M. P., Pilcher, C. D., & Murphy, G. Journal of Acquired Immune Deficiency Syndromes (1999), 76(5):547–555, 2017.
doi  abstract   bibtex   
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.
@article{grebe_infection_2017,
	title = {Infection {Staging} and {Incidence} {Surveillance} {Applications} of {High} {Dynamic} {Range} {Diagnostic} {Immuno}-{Assay} {Platforms}},
	volume = {76},
	issn = {1944-7884},
	doi = {10.1097/QAI.0000000000001537},
	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 ≈ 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.},
	language = {eng},
	number = {5},
	journal = {Journal of Acquired Immune Deficiency Syndromes (1999)},
	author = {Grebe, Eduard and Welte, Alex and Hall, Jake and Keating, Sheila M. and Facente, Shelley N. and Marson, Kara and Martin, Jeffrey N. and Little, Susan J. and Price, Matthew A. and Kallas, Esper G. and Busch, Michael P. and Pilcher, Christopher D. and Murphy, Gary},
	year = {2017},
	pmid = {28914669},
	pmcid = {PMC5680100},
	keywords = {Diagnostic Tests, Routine, HIV Antibodies, HIV Antigens, HIV Infections, HIV-1, Humans, Immunoassay, Incidence, Population Surveillance, Sensitivity and Specificity, Time Factors},
	pages = {547--555},
}

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