Frontiers in Immunology · Oct 30, 2026
HIV reservoir and chronic inflammation in men with subclinical cardiovascular disease
By Nicolas Sluis-Cremer, Aiymkul Ashimkhanova, Yijia Li et al.
Introduction: Atherosclerotic cardiovascular disease (CVD) is more prevalent in people with HIV-1 than people without HIV, despite effective antiretroviral therapy (ART). The underlying reasons remain unclear. Chronic inflammation, which damages vascular endothelium and promotes plaque formation, is a major contributor to atherosclerosis. Methods: In this cross-sectional, exploratory study, we investigated associations among the HIV-1 reservoir, inflammation, and subclinical atherosclerosis in men with HIV-1 (MWH) in the Pittsburgh Clinical Research Site of the Multicenter AIDS Cohort Study – Women's Interagency HIV Study Combined Cohort Study (MWCCS). Participants had undergone cardiovascular imaging studies (ultrasound and CT) and were categorized based on carotid artery ultrasound-based CVD risk stratification (age-adjusted intima-media thickness, presence of focal plaque). Results: We report that MWH with greater CVD risk had higher levels of intact HIV-1 provirus. Moreover, matrix metalloproteinase 9 levels were positively associated with subclinical atherosclerosis. Single-cell RNA sequencing analysis of peripheral blood immune cells showed enrichment of MTORC1, non-canonical NF-kB, senescence-associated, monocyte state 1, and HIV-1-associated transcriptional programs in monocytes, and enrichment of interferon signaling in T cells in the high-risk carotid ultrasound group. Conclusion: A higher intact HIV-1 proviral burden in this cross-sectional cohort showed associations with subclinical atherosclerosis, as well as inflammatory and senescence-associated transcriptional programs in circulating immune cells.