HIV感染者およびアテローム性動脈硬化症、動脈炎症、造血活動におけるクローナル造血

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular disease (CVD) in the general population and is more common among people with HIV (PWH). The mechanisms by which CHIP contributes to atherosclerosis in PWH are unknown. We hypothesized that CHIP is associated with carotid atherosclerosis, arterial inflammation, and hematopoietic activity among PWH.

In a cohort study, we studied PWH ages 31-74 years. CHIP mutations were detected with a validated targeted sequencing assay. Carotid intima-media thickness (IMT) was measured longitudinally with ultrasound. Aortic inflammation and lymph node activity were assessed cross-sectionally using ¹⁸ F-FDG-PET. Inflammatory biomarkers were measured using multiplex electrochemiluminescence assay. Linear regression was employed, with adjustments for traditional and HIV-related factors.

We included 230 PWH (52±9 years, 7% female); 32 (14%) had CHIP with median variant allele fraction of 2.8%. Common mutations were in DNM3TA (n=21) and TET2 (n=6). Age was associated with CHIP (OR 2.0 per decade older, 95% CI 1.3-3.01; p=0.002). Among 166 participants with IMT measurements (CHIP=23), CHIP was not associated with IMT (p=0.21; unchanged after adjustment). Among 80 with FDG-PET, CHIP (n=12) was not associated with arterial inflammation (p=0.89), but was associated with higher lymph node metabolic activity (p=0.03) that was attenuated in reference to background activity and adjusted for risk factors. CHIP was not associated with soluble inflammatory markers or viral persistence markers.

Among PWH, CHIP mutations were not associated with subclinical atherosclerosis, arterial inflammation, or soluble inflammatory markers but were related to hematopoietic activity. The mechanism by which CHIP increases HIV-associated atherosclerosis may preferentially involve lymph nodes and merits additional evaluation.