Quantifying excess TB prevalence among people living with HIV on ART in the universal ART era: Evidence from a TB prevalence survey in Zambia and South Africa.

Despite widespread antiretroviral therapy (ART) scale-up, tuberculosis (TB) remains a leading cause of morbidity and mortality among people living with HIV (PLHIV). While ART reduces TB incidence among PLHIV, its effect on TB prevalence remains less clear. We estimated the difference in TB prevalence between PLHIV on ART and their counterfactual HIV-negative state, quantifying their proportionate contribution to overall TB prevalence in high-HIV settings across Southern Africa. Using data from the 2019-2021 TREATS TB prevalence survey, a cross-sectional survey of adults aged ≥15 years in 21 communities in Zambia and South Africa (SA) (Western Cape province), we applied Rubin's "potential outcomes" framework and inverse probability of treatment weighting, with propensity scores estimated using logistic regression to control for measured confounding. We estimated the average treatment effect on the treated (ATT) as the TB prevalence difference (PD) among PLHIV on ART compared to a counterfactual scenario where the same individuals were HIV-negative. Among 43,617 analysed, 6,612 (15.2%) were PLHIV on ART and 37,005 (84.8%) tested HIV-negative. After adjusting for confounding, PLHIV on ART had higher TB prevalence than the counterfactual HIV-negative scenario (ATT: PD = 0.53%; 95% confidence interval [CI]: 0.19, 0.87). There was statistical evidence of an effect in the Zambian communities (ATT: PD = 0.49%; 95% CI: 0.14, 0.85), but the evidence was weaker in SA communities (ATT: PD = 0.56%; 95% CI: -0.15, 1.26). At the population level, PLHIV on ART contributed an absolute excess of 0.08% to overall TB prevalence, representing a 9.3% proportionate increase, which was larger in Zambian (14.8%) than in SA (5.6%) communities due to background TB prevalence differences. PLHIV on ART remain at elevated risk of prevalent TB, contributing considerably to overall TB prevalence, underscoring the need for continued, targeted TB prevention, screening, and treatment strategies for all PLHIV in settings with a high burden of both TB and HIV. Trial registration ClinicalTrials.gov NCT03739736.