Detection of tuberculosis recurrence, diagnosis and treatment response by a blood transcriptomic risk signature in HIV-infected persons on antiretroviral therapy
Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers Media
Abstract
ENGLISH 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.
Description
CITATION: 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.
The original publication is available at https://www.frontiersin.org
The original publication is available at https://www.frontiersin.org
Keywords
Tuberculosis -- Risk factors, HIV-positive persons, Tuberculosis -- Diagnosis, Anti-retroviral agents
Citation
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