Abstract 14442: Tuberculosis-Specific Cell-Mediated Immune Responses Are Associated With Coronary Artery Atherosclerosis Among Persons With and Without HIV in Uganda

Abstract

Introduction: Latent tuberculosis infection (LTBI) has been associated with increased odds of acute myocardial infarction. Here we assessed the relationship between subclinical coronary atherosclerosis, LTBI status, and Mycobacterium tuberculosis ( Mtb )-specific cell-mediated responses. Hypothesis: LTBI and the magnitude of Mtb -specific cell-mediated responses are associated with increased rates of subclinical coronary artery disease (CAD). Methods: Cross-sectional study within a cohort of HIV-infected and -uninfected participants enrolled at the Joint Clinical Research Centre in Kampala, Uganda. Participants were ≥45 years with at least one risk factor for cardiovascular disease. Persons living with HIV (PLWH) were on stable antiretroviral therapy with HIV viral load ≤1,000 copies/mL within the 6 months prior to study entry. Participants underwent QuantiFERON®-TB Gold (QFT) testing to define LTBI status. Interferon-γ (IFN-γ) cell-mediated responses to Mtb antigens contained in the QFT TB tube were extracted. Participants underwent coronary computed tomography angiography (CCTA) utilizing a 128-slice Siemen’s scanner. Obstructive CAD was defined as having at least one coronary segment with plaque causing ≥ 50% luminal stenosis (CAD-RADS ≥3). Results: Of 138 participants, 66 (48%) had LTBI (17 PLWH and 49 HIV-uninfected), and 72 (52%) were non-LTBI (38 PLWH and 34 HIV-uninfected). Median age was 57 years; 91 (66%) were female; 120 (87%) had hypertension, 45 (33%) had diabetes mellitus, 24 (17%) had dyslipidemia, and 7 (5%) used tobacco. Median CD4 count was 569 cells/uL in PLWH. Prevalence of obstructive CAD was 9% in LTBI vs. 3% in non-LTBI; p =0.152. Mtb -specific responses were higher in persons with obstructive CAD compared to those without it (IFN-γ IU/mL median [IQR]; 5 [0.4 - 9.6] vs. 0.3 [0.1 - 2.9]; p =0.04). Mtb -specific responses remained associated with obstructive CAD after adjusting for age, sex, HIV status, cholesterol, hypertension, tobacco use, and diabetes mellitus (adjusted OR, 1.33; 95% CI; 1.04 - 1.7). Conclusions: Higher Mtb -specific cell-mediated responses were associated with obstructive CAD. Our findings suggest that Mtb contributes to coronary plaque burden independently of HIV and cardiovascular risk factors.