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Clinical Predictors of Pulmonary Tuberculosis Among South African Adults With HIV
25 Pages Posted: 19 Nov 2021
More...Abstract
Background: Tuberculosis (TB) clinical prediction rules rely on presence of symptoms, however many undiagnosed cases in the community are asymptomatic. This study explored utility of clinical factors in predicting TB among people with HIV not seeking care.
Methods: Baseline data were analysed from an observational cohort of ambulant adults with HIV in South Africa. Participants were tested for Mycobacterium tuberculosis (Mtb) sensitisation (interferon-γ release assay) and microbiologically-confirmed prevalent pulmonary TB disease at baseline, and actively surveilled for incident TB through 15 months. Multivariable LASSO regression with post-selection inference was used to test associations with Mtb sensitisation and TB disease.
Findings: Among 851 participants, 94·5% were asymptomatic and 45·9% sensitised to Mtb. TB prevalence was 2·0% and incidence 2·3/100 person-years. Study site was associated with baseline Mtb sensitisation (p<0·001), prevalent (p<0·001), and incident TB disease (p=0·037). Independent of site, participants with lower CD4 counts (per 50 cells/mm3, aOR 1·48, 95%CI 1·12-1·77) and without TB disease (0·80, 0·69-0·94) had reduced IGRA positivity; no variables were independently associated with prevalent TB. Mixed ancestry (aHR 1·49, 95%CI 1·30->1000) and antiretroviral initiation (1·48, 1·01-929·93) were independently associated with incident TB. Models incorporating clinical features alone performed poorly in diagnosing prevalent (AUC 0·65, 95%CI 0·44-0·85) or predicting progression to incident (0·67, 0·46-0·88) TB.
Interpretation: Immunological variables, CD4 count and antiretroviral initiation indicative of immune reconstitution, most significantly predicted Mtb sensitisation and TB disease. Inadequate performance of clinical prediction models may reflect predominantly subclinical disease diagnosed in this setting and unmeasured local factors affecting transmission and progression.
Funding Information: The CORTIS-HR study was funded by the Bill & Melinda Gates Foundation (OPP1151915) and by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council (SAMRC) with funds received from the South African Department of Science and Technology. The regulatory sponsor was the University of Cape Town
Declaration of Interests: AFG, GW, GC, TJS, and MH report grants from the Bill & Melinda Gates Foundation, during the conduct of the study. GW and TJS report grants from the South African Medical Research Council, during the conduct of the study. TJS reports a patent pending for the RISK11 signature. All other authors declare no competing interests.
Ethics Approval Statement: The study protocol was approved by the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee (HREC 812/2017 and 648/2016) and written informed consent was obtained from all participants.
Keywords: tuberculosis, Mycobacterium tuberculosis, HIV, clinical, model, prediction, risk, diagnosis, subclinical, case-finding
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