Detection of tuberculosis recurrence, diagnosis and treatment response by a blood transcriptomic risk signature in HIV-infected persons on antiretroviral therapy

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dc.contributor.authorDarboe, Fatoumattaen_ZA
dc.contributor.authorMbandi, Stanley Kimbungen_ZA
dc.contributor.authorNaidoo, Kogieleumen_ZA
dc.contributor.authorYende-Zuma, Nonhlanhlaen_ZA
dc.contributor.authorLewis, Laraen_ZA
dc.contributor.authorThompson, Ethan G.en_ZA
dc.contributor.authorDuffy, Fergal J.en_ZA
dc.contributor.authorFishe, Michelleen_ZA
dc.contributor.authorFilander, Elizabethen_ZA
dc.contributor.authorVan Rooyen, Micheleen_ZA
dc.contributor.authorBilek, Nicoleen_ZA
dc.contributor.authorMabwe, Simbarasheen_ZA
dc.contributor.authorMcKinnon, Lyle R.en_ZA
dc.contributor.authorChegou, Novelen_ZA
dc.contributor.authorLoxton, Andreen_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorTromp, Gerarden_ZA
dc.contributor.authorPadayatchi, Nesrien_ZA
dc.contributor.authorGovender, Dhineshreeen_ZA
dc.contributor.authorHatherill, Marken_ZA
dc.contributor.authorKarim, Salim Abdoolen_ZA
dc.contributor.authorZak, Daniel E.en_ZA
dc.contributor.authorPenn-Nicholson, Adamen_ZA
dc.contributor.authorScriba, Thomas J.en_ZA
dc.contributor.authorSATVI Clinical Immunology Teamen_ZA
dc.date.accessioned2021-11-03T14:10:45Z
dc.date.available2021-11-03T14:10:45Z
dc.date.issued2019
dc.descriptionCITATION: Darboe, F., et al. 2019. Detection of tuberculosis recurrence, diagnosis and treatment response by a blood transcriptomic risk signature in HIV-infected persons on antiretroviral therapy. Frontiers in Microbiology, 10:1441, doi:10.3389/fmicb.2019.01441.
dc.descriptionThe original publication is available at https://www.frontiersin.org
dc.description.abstractENGLISH ABSTRACT: HIV-infected individuals are at high risk of tuberculosis disease and those with prior tuberculosis episodes are at even higher risk of disease recurrence. A non-sputum biomarker that identifies individuals at highest tuberculosis risk would allow targeted microbiological testing and appropriate treatment and also guide need for prolonged therapy. We determined the utility of a previously developed whole blood transcriptomic correlate of risk (COR) signature for (1) predicting incident recurrent tuberculosis, (2) tuberculosis diagnosis and (3) its potential utility for tuberculosis treatment monitoring in HIV-infected individuals. We retrieved cryopreserved blood specimens from three previously completed clinical studies and measured the COR signature by quantitative microfluidic real-time-PCR. The signature differentiated recurrent tuberculosis progressors from non-progressors within 3 months of diagnosis with an area under the Receiver-operating characteristic (ROC) curve (AUC) of 0.72 (95% confidence interval (CI), 0.58–0.85) amongst HIV-infected individuals on antiretroviral therapy (ART). Twenty-five of 43 progressors (58%) were asymptomatic at microbiological diagnosis and thus had subclinical disease. The signature showed excellent diagnostic discrimination between HIV-uninfected tuberculosis cases and controls (AUC 0.97; 95%CI 0.94–1). Performance was lower in HIV-infected individuals (AUC 0.83; 95%CI 0.81–0.96) and signature scores were directly associated with HIV viral loads. Tuberculosis treatment response in HIV-infected individuals on ART with a new recurrent tuberculosis diagnosis was also assessed. Signature scores decreased significantly during treatment. However, pre-treatment scores could not differentiate between those who became sputum negative before and after 2 months. Direct application of the unmodified blood transcriptomic COR signature detected subclinical and active tuberculosis by blind validation in HIV-infected individuals. However, prognostic performance for recurrent tuberculosis, and performance as diagnostic and as treatment monitoring tool in HIV-infected persons was inferior to published results from HIV-negative cohorts. Our results suggest that performance of transcriptomic signatures comprising interferon stimulated genes are negatively affected in HIV-infected individuals, especially in those with incompletely suppressed viral loads.en_ZA
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fmicb.2019.01441/full
dc.description.versionPublisher's version
dc.format.extent16 pagesen_ZA
dc.identifier.citationDarboe, F., et al. 2019. Detection of tuberculosis recurrence, diagnosis and treatment response by a blood transcriptomic risk signature in HIV-infected persons on antiretroviral therapy. Frontiers in Microbiology, 10:1441, doi:10.3389/fmicb.2019.01441
dc.identifier.issn1664-302X (online)
dc.identifier.otherdoi:10.3389/fmicb.2019.01441
dc.identifier.urihttp://hdl.handle.net/10019.1/123352
dc.language.isoen_ZAen_ZA
dc.publisherFrontiers Mediaen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTuberculosis -- Risk factorsen_ZA
dc.subjectHIV-positive personsen_ZA
dc.subjectTuberculosis -- Diagnosisen_ZA
dc.subjectAnti-retroviral agentsen_ZA
dc.titleDetection of tuberculosis recurrence, diagnosis and treatment response by a blood transcriptomic risk signature in HIV-infected persons on antiretroviral therapyen_ZA
dc.typeArticleen_ZA
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