Sex-Dimorphic Associations of Prior Tuberculosis with Hypertension and Inflammatory Signature in People with HIV: a pilot study

Abstract

Background: People with HIV (PWH) experience an increased burden of cardiovascular disease (CVD), partly driven by chronic immune activation despite antiretroviral therapy (ART). Tuberculosis (TB), a frequent co-infection, may leave persistent inflammatory sequelae even after cure, potentially accelerating hypertension and cardiovascular risk. Evidence on long-term cardiometabolic consequences of prior TB in virally suppressed PWH, particularly sex-specific effects, remains limited. Methods: In a pilot cross-sectional study of 318 PWH, we compared demographics, cardiovascular parameters, and a panel of circulating inflammatory biomarkers between those with and without a history of TB. Logistic regression was used to identify factors associated with TB history in the whole cohort and stratified by sex. Results: In the 31 participants (9.7%) with prior TB, univariate analysis identified significant associations with older age, hypertension, longer ART duration, and elevated IL-6 and soluble ST2. Hypertension was strongly associated with TB history in females (OR 4.41, 95% CI: 3.41 (1.57, 7.41) p=0.003) but not males. In multivariate models adjusted for clinical variables, longer ART duration remained an independent correlate in the full cohort. Sex-stratified multivariate analysis revealed that lower IFN-γ was associated with TB history in males (AOR 0.99, p=0.048), while lower IL-5 was associated with TB history in females (AOR 0.99, p=0.042). Conclusion: A history of TB is associated with hypertension in PWH, particularly among females, and is linked to sex-specific differences in residual inflammatory pathways. These findings suggest that prior TB may contribute to cardiovascular risk in a sex-disparate manner, warranting further investigation.