Background
Surveys suggest a high burden of asymptomatic TB, but its epidemiology, especially among people with HIV (PWH), is not well defined. We examined this in the CoVPN 3008 TB substudy (NCT05168813).
Methods
From 10/2024 to 03/2025, we conducted a cross-sectional study, enrolling participants from CoVPN 3008 at 38 sites in Botswana, Kenya, Malawi, South Africa, Uganda and Zambia. Regardless of symptoms, all underwent TB screening: symptoms, history, chest radiography, sputum smear, Xpert Ultra, and culture. PWH had CD4 count and HIV viral load testing. Participants were defined as TB cases (Xpert Ultra or culture positive), TB negative (negative microbiology and no clinical/radiologic evidence), or indeterminate. TB was classified as symptomatic or asymptomatic using WHO’s 4-symptom screen. To not bias symptom assessment, those on TB treatment were excluded from analyses. Characteristics were compared using Fisher’s exact, Chi-square, and Wilcoxon rank-sum tests.
Results
Of 5,934 enrolled, 5,694 were analyzed: 74% female, median age was 42 (IQR 35-49), and median BMI was 25.3 (IQR 21.2-31.4). PWH were 4,983 (88%) with median CD4 724 cells/µL (IQR 510-960); 3.6% had CD4<200 cells/µL, and 16% HIV viraemia. Prior TB was reported by 1,080 (19%). TB was confirmed in 108 (1.9%): 26 (0.5%) symptomatic and 82 (1.4%) asymptomatic. 4,660 (81.8%) were TB negative and 926 (16.0%) indeterminate. In adjusted analysis, TB prevalence was higher among males (4.0% vs 1.7%, p<0.001), those with lower BMI (median 22.0 vs 25.7, p<0.001), prior TB ever (4.2% vs 1.7%, p<0.001), smoking (3.4% vs 1.8%, p=0.006), and at-risk drinking (3.0% vs 1.7%, p=0.045), but did not differ by HIV status (2.1% PWH vs 3.3% HIV-negative, p=0.415). No significant differences were observed between symptomatic and asymptomatic TB cases, including by sex, age, HIV status, BMI, education, smoking, drinking, or prior TB.
Conclusions
In a large, diverse African cohort, nearly 2% had undiagnosed TB, three-quarters asymptomatic and indistinguishable from symptomatic cases by baseline characteristics despite potential infectiousness. These findings underscore the limits of symptom-based screening and the urgent need to better understand asymptomatic TB and identify prognostic biomarkers to predict future disease, including asymptomatic TB, to enable more targeted prevention efforts and support more efficient design of vaccine and other efficacy trials. The lack of difference by HIV status likely reflects in part robust HIV control among PWH.