Abstract 15748: Association of Clonal Hematopoiesis in the Setting of Human Immunodeficiency Virus Infection With Subclinical Atherosclerosis and Vascular Inflammation

Abstract

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular disease (CVD) and common in HIV, but whether CHIP contributes to atherosclerosis in HIV is unknown. We hypothesized CHIP is associated with atherosclerosis and arterial inflammation among people with HIV (PWH). Methods: We studied treated, suppressed PWH ages 35-70 years old with ≥1 CVD risk factor. CHIP mutations were detected with a validated targeted sequencing assay. We measured carotid intima-media thickness (IMT) longitudinally with ultrasound and aortic inflammation and lymph node activity using cross-sectional 18 F-FDG-PET. Inflammatory biomarkers were measured with a multiplex electrochemiluminescence assay. We used linear regression with adjustment for age, sex, nadir CD4 count, smoking, hypertension, diabetes, and hyperlipidemia. Results: We included 231 PWH (52±9 years, 7% female). 32 (14%) had CHIP with median variant allele fraction of 3.1%. Common mutations were in DNM3TA (n=21) and TET2 (n=6). Only age was associated with CHIP (OR 2.3 per decade older, 95%CI 1.2-3.9; p=0.003). Among N=165 (CHIP=22), mean IMT was 1.0 mm with and without CHIP (p=0.63), unchanged after adjustment (Figure). CHIP was not associated with prevalent or incident plaque. Over 3.2 years, IMT progression was faster among those with CHIP (0.033 mm/year; p=0.10), attenuated after adjustment (0.022 mm/year; p=0.27). Among 80 with FDG-PET, CHIP (n=12) was associated with higher lymph node activity (SUV p=0.04) that was attenuated in reference to background activity and adjusted for risk factors. CHIP was not associated with arterial inflammation (p=0.83), inflammatory markers, or viral persistence markers. Conclusions: Among PWH, CHIP mutations were not associated with subclinical atherosclerosis or arterial inflammation, proposed mechanisms of how CHIP could cause CVD. Clinical outcomes studies are needed to ascertain the impact of CHIP on CVD in HIV.