Monocyte activation patterns tracked with peri-coronary inflammation on coronary CT in HIV and non-HIV adults
Peri-coronary inflammation was not just a radiologic signal in this cohort. It lined up with a specific pattern of circulating monocyte activation and chemokine receptor expression, and the associations were not identical in people with and without HIV.
The study focused on fat attenuation index (FAI), a coronary computed tomography angiography biomarker that captures inflammatory change in perivascular fat around the proximal left anterior descending artery (LAD) and right coronary artery (RCA). In adults without known cardiovascular disease, higher FAI has been linked to future cardiac risk, making it a useful window into vascular inflammation before overt atherosclerotic disease appears. Here, investigators paired that imaging readout with detailed flow cytometric profiling of monocyte subsets and surface markers in 58 virologically suppressed people with HIV and 16 people without HIV.
The cohort design matters because every participant was free of known cardiovascular disease at enrollment, and HIV-negative participants were age- and sex-matched to those with HIV. Everyone underwent the same coronary CT angiography workflow, and all blood-based testing was performed with the same flow cytometry approach. That gave the analysis a narrow but clinically important focus: how immune cell phenotype relates to early coronary inflammation when overt clinical disease has not yet declared itself.
CD40 rose in HIV, while HLA-DR fell across monocyte subsets
Several immune differences separated the groups before the imaging associations were even modeled. Frequency and expression of CD40 were higher in people with HIV, while HLA-DR expression was lower across all monocyte subsets compared with people without HIV. In practical terms, the monocyte compartment in suppressed HIV infection still carried a distinct activation and antigen-presentation signature despite viral control on antiretroviral therapy.
The study evaluated classical, intermediate, and non-classical monocytes, with additional attention to CD16dim intermediate/inflammatory and CD16neg classical populations. That level of granularity is clinically useful because monocytes are not a single uniform pool. Classical cells are usually tied to recruitment and inflammatory signaling through CCR2, intermediate cells tend to reflect immune activation and antigen presentation, and non-classical cells are often linked to vascular surveillance and patrolling behavior. The data in this cohort showed that those distinctions mapped onto coronary inflammation rather than remaining purely descriptive immunology.
LAD and RCA inflammation aligned with different monocyte markers
The most direct imaging-immunology links emerged in the multivariable models. CD38+ intermediate monocytes were associated with worse LAD FAI, while CD38+ non-classical monocytes correlated with worse RCA FAI. CCR2 expression on total classical monocytes, as well as on CD16dim and CD16neg subsets, correlated with worse RCA and LAD FAI. In contrast, CX3CR1+ monocytes and CD40+ subsets correlated with improved RCA FAI in adjusted analyses.
Those patterns are biologically coherent even if they are not yet causal. CCR2 marks cells primed for recruitment into inflamed tissue, and a higher CCR2 signal alongside worse FAI suggests a circulating pool poised to traffic into the coronary microenvironment. CD38 is commonly treated as an activation marker, so its association with higher FAI in intermediate and non-classical subsets fits with a state of ongoing immune engagement. The protective direction seen with CX3CR1-positive and CD40-positive subsets is less straightforward and will need mechanistic work to determine whether those cells represent a more regulated surveillance phenotype, a compensatory response, or simply a marker profile that tracks with a different inflammatory state.
One result stands out because it links systemic immune biology to vessel-specific inflammation rather than to generalized risk. The LAD and RCA did not behave identically.
HIV serostatus modified the monocyte–FAI relationship
The investigators tested interaction terms to determine whether HIV status changed the relationship between monocyte phenotype and peri-coronary inflammation. It did. The associations between FAI and monocyte markers were influenced by HIV serostatus, reinforcing the idea that chronic HIV infection leaves a measurable imprint on the immune system even when viremia is suppressed.
This is consistent with the broader clinical picture in which people with HIV remain at higher cardiovascular risk than HIV-negative peers despite effective antiretroviral therapy. Persistent immune activation, altered monocyte trafficking, and inflammatory signaling likely contribute to that excess risk. The current analysis does not claim that any one monocyte subset causes coronary inflammation, but it does show that the circulating monocyte compartment carries information about coronary inflammatory burden, and that information differs according to HIV status.
The investigators also linked these findings to prior work from the same cohort showing associations between FAI and other inflammatory markers and T-cell activation measures. That continuity strengthens the case for FAI as a vascular readout of immune activation rather than a stand-alone imaging curiosity. In this setting, FAI appears to capture the coronary footprint of a broader inflammatory state.
A cross-sectional design with a narrow clinical lens
This was a cross-sectional analysis nested within a prospective observational cohort, so the study cannot establish temporal order or prove that any monocyte phenotype drives the coronary signal. The sample was also modest, especially in the HIV-negative group, and the cohort was selected to exclude people with overt cardiovascular disease or major competing clinical instability. Those design choices improve biological clarity, but they also limit generalizability to broader clinical populations.
Eligibility restrictions were substantial. Participants with unstable coronary syndromes, marked blood pressure elevation, poorly controlled diabetes, significant anemia, reduced creatinine clearance, recent illicit drug use, major conduction disease, reduced ejection fraction, severe asthma, or contraindications to coronary CT angiography were excluded. For the imaging analysis, five HIV-negative participants with BMI above 40 were removed to improve comparability because BMI had the strongest association with FAI in the cohort. Those choices reduce confounding, yet they also narrow the window into real-world care.
Still, the study offers a clinically relevant signal: FAI tracked with monocyte activation and chemokine receptor expression in a way that reflected HIV status and coronary territory. If future studies confirm these relationships longitudinally, FAI and monocyte phenotyping could help identify which patients are carrying silent vascular inflammation before structural coronary disease becomes evident. The next step is not another association table alone, but a mechanistic follow-up that asks whether these monocyte states predict progression, plaque behavior, or treatment responsiveness over time.