Open Forum Infect Dis. 2026 Mar 9;13(3):ofag107. doi: 10.1093/ofid/ofag107. eCollection 2026 Mar.
ABSTRACT
BACKGROUND: People living with HIV-1 (PLWH) have an increased risk of cardiovascular disease (CVD), influenced by chronic inflammation, immune dysregulation, and antiretroviral therapy (ART). B cells regulate immune responses, but their contribution to HIV-associated atherosclerosis remains poorly defined.
METHODS: In a cross-sectional study, we enrolled 40 PLWH and 60 people without HIV (PWoH) in Uganda, matched 1:1.5 for age and CVD risk. Peripheral blood mononuclear cells were profiled by mass cytometry to define immune cell subsets. Coronary computed tomography angiography quantified coronary artery disease using the segment stenosis score (SSS). We used multivariable hurdle regression to estimate the effect sizes of immune clusters, atherosclerotic cardiovascular disease (ASCVD) risk score, HIV status, and gender.
RESULTS: Median age was 60 years, with no difference by HIV status. People living with HIV had a lower proportion of CCR7- naïve B cells than PWoH (median 1.5% vs 1.8%; P-value adjusted [padj] = .03). Across all participants, higher CCR7- naïve B cells (ratio = 0.55, P = .02), CXCR3+CX3CR1+ B cells (ratio = 0.54, P = .03), and plasmablasts (ratio = 0.57, P = .003) were associated with lower SSS. HIV-positive status was linked to nearly 3-fold higher SSS (P < .01). In stratified analyses, classical monocytes (CD14+CD16-) correlated with higher SSS among PLWH. When classical monocytes were held at the median, higher CCR7- naïve B cells were protective in PLWH (ratio = 0.55, P = .02).
CONCLUSIONS: This exploratory study suggests that lower frequencies of naïve B cells in PLWH are associated with differences in subclinical atherosclerosis. However, the mechanisms cannot be inferred from this study.
PMID:41859698 | PMC:PMC12996881 | DOI:10.1093/ofid/ofag107