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

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dc.contributor.authorGrebe, Eduarden_ZA
dc.contributor.authorWelte, Alexen_ZA
dc.contributor.authorHall, Jakeen_ZA
dc.contributor.authorKeating, Sheilaen_ZA
dc.contributor.authorFacente, Shelleyen_ZA
dc.contributor.authorMarson, Karaen_ZA
dc.contributor.authorMartin, Jeffreyen_ZA
dc.contributor.authorLittle, Susanen_ZA
dc.contributor.authorPrice, Matthewen_ZA
dc.contributor.authorKallas, Esperen_ZA
dc.contributor.authorBusch, Michaelen_ZA
dc.contributor.authorPilcher, Christopheren_ZA
dc.contributor.authorMurphy, Garyen_ZA
dc.contributor.otherConsortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA)en_ZA
dc.contributor.otherSouth African Centre for Epidemiological Modelling and Analysis (SACEMA)
dc.date.accessioned2017-05-19T13:01:57Z
dc.date.available2017-05-19T13:01:57Z
dc.date.issued2017-12
dc.descriptionCITATION: 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. on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA). Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms. JAIDS Journal of Acquired Immune Deficiency Syndromes, 76(5):547-555. doi:10.1097/QAI.0000000000001537.en_ZA
dc.descriptionThe original publication is available at https://journals.lww.com/jaids/pages/default.aspxen_ZA
dc.description.abstractBackground: 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.
dc.description.urihttps://journals.lww.com/jaids/Fulltext/2017/12150/Infection_Staging_and_Incidence_Surveillance.15.aspx
dc.description.versionPreprint (first submitted version)en_ZA
dc.description.versionPublishers versionen_ZA
dc.identifier.citationGrebe, 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. on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA). Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms. JAIDS Journal of Acquired Immune Deficiency Syndromes, 76(5):547-555. doi:10.1097/QAI.0000000000001537.en_ZA
dc.identifier.issn1944-7884 (online)
dc.identifier.issn1525-4135 (print)
dc.identifier.otherdoi:10.1097/QAI.0000000000001537
dc.identifier.urihttp://hdl.handle.net/10019.1/101540
dc.publisherWolters Kluweren_ZA
dc.rights.holderAuthors retain copyright
dc.subjectInfection timingen_ZA
dc.subjectInfection stagingen_ZA
dc.subjectStaging assaysen_ZA
dc.subjectDiagnostic assaysen_ZA
dc.titleInfection staging and incidence surveillance applications of high dynamic range diagnostic immuno-assay platformsen_ZA
dc.typeArticleen_ZA
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