Clinical predictors of pulmonary tuberculosis among South African adults with HIV

Background Tuberculosis (TB) clinical prediction rules rely on presence of symptoms, however many undiagnosed cases in the community are asymptomatic. This study aimed to explore the 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-gamma release assay, IGRA) 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 Between March 22, 2017, and May 15, 2018, 861 participants were enrolled; Among 851 participants included in the analysis, 94 center dot 5% were asymptomatic and 45 center dot 9% sensitised to Mtb. TB prevalence was 2 center dot 0% at baseline and incidence 2 cent 3/100 person-years through 15 months follow-up. Study site was associated with baseline Mtb sensitisation (p < 0 center dot 001), prevalent (p < 0 center dot 001), and incident TB disease (p = 0 center dot 037). Independent of site, higher CD4 counts (per 50 cells/mm3, aOR 1 center dot 48, 95%CI 1 center dot 12-1 center dot 77, p = 0 center dot 006) were associated with increased IGRA positivity, and participants without TB disease (aOR 0 center dot 80, 95%CI 0 center dot 69-0 center dot 94, p = 0 center dot 006) had reduced IGRA positivity; no variables were independently associated with prevalent TB. Mixed ancestry (aHR 1 center dot 49, 95%CI 1 center dot 30-> 1000, p = 0 center dot 005) and antiretroviral initiation (aHR 1 center dot 48, 95%CI 1 center dot 01-929 center dot 93, p = 0 center dot 023) were independently associated with incident TB. Models incorporating clinical features alone performed poorly in diagnosing prevalent (AUC 0 center dot 65, 95%CI 0 center dot 44-0 center dot 85) or predicting progression to incident (0 center dot 67, 0 center dot 46-0 center dot 88) TB. Interpretation CD4 count and antiretroviral initiation, proxies for immune status and HIV stage, were associated with Mtb sensitisation and TB disease. Inadequate performance of clinical prediction models may reflect predominantly subclinical disease diagnosed in this setting and unmeasured local site factors affecting transmission and progression. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)