P eople with HIV infection now live longer and increasingly experience age-related diseases such as coronary artery disease. Studies from North America and Europe showed a greater myocardial infarction risk ratio varying from 1.5 to 2.1 in people living with HIV (PLWH) compared with the general population (1-3). Other than age, overrepresentation of traditional cardiovascular risk factors such as smoking, dyslipidemia, hypertension, and diabetes (1,4) probably also contributes to the increased incidence of cardiovascular disease in PLWH, although this increased incidence persists after adjustment for these risk factors (1,2). An impact of antiretroviral therapy on coronary artery disease has been discussed in multiple studies (5,6). Mechanisms such as inflammation and immune dysfunction seem to have a role along the pathways to this higher risk of cardiovascular disease (7,8).Coronary CT angiography is a noninvasive imaging option of choice for the characterization, quantification, and monitoring of coronary HIV-related atherosclerosis in clinical studies and may provide robust anatomic substrates suitable for correlative assessment in mechanistic studies. Controversial findings exist regarding the higher rates of noncalcified coronary plaque in PLWH compared with healthy volunteers without HIV (9-13). In our prospective study nested in a large cohort, we aimed to compare the burden and CT characteristics of subclinical coronary atherosclerotic plaque in asymptomatic PLWH without known cardiovascular disease compared with healthy volunteers without HIV. We hypothesized Background: People living with HIV (PLWH) have a higher risk of myocardial infarction. Coronary atherosclerotic plaque CT characterization helps to predict cardiovascular risk.Purpose: To measure CT characteristics of coronary plaque in PLWH without known cardiovascular disease and healthy volunteers without HIV. Materials and Methods:In this prospective study, noncontrast CT (all participants, n = 265) was used for coronary artery calcium (CAC) scoring in asymptomatic PLWH and healthy volunteers without HIV, without known cardiovascular disease, from 2012 to 2019. At coronary CT angiography (n = 233), prevalence, frequency, and volume of calcified, mixed, and noncalcified plaque were measured. Poisson regressions were used with adjustment for cardiovascular risk factors.Results: There were 181 PLWH (mean age, 56 years 6 7; 167 men) and 84 healthy volunteers (mean age, 57 years 6 8; 65 men) evaluated by using noncontrast CT. CT angiography was performed in 155 PLWH and 78 healthy volunteers. Median 10-year Framingham risk score was not different between PLWH and healthy volunteers (10% vs 9%, respectively;

Background Coronary computed tomography angiography (CTA) allows the evaluation of coronary plaque volume and low attenuation (lipid-rich) component, for plaque vulnerability assessment. Purpose To determine the effect of iterative reconstruction (IR) on coronary plaque volume and composition. Material and Methods Consecutive patients without coronary artery disease were prospectively enrolled for 256-slice CT. Images were reconstructed with both filtered back projection (FBP) and a hybrid IR algorithm (iDose, Philips) levels 1, 3, 5, and 7. Coronary plaques were assessed according to predefined Hounsfield unit (HU) attenuation intervals, for total plaque and HU-interval volumes. Results Fifty-three patients (mean age, 53.6 years) were included. Noise was significantly decreased and signal-to-noise ratio (SNR) / contrast-to-noise (CNR) were both significantly improved at all IR levels in comparison to FBP. Plaque characterization was performed in 41 patients for a total of 125 plaques. Total plaque volume ranged from 104.4 ± 120.7 to 107.4 ± 128.9 mm and low attenuation plaque component from 40.5 ± 54.7 to 43.5 ± 58.9 mm, with no statistically significant differences between all IR levels and FBP ( P = 0.786 and P ≥ 0.078, respectively). Conclusion IR improved image quality. Total and low attenuation plaque volumes were similar using either IR or FBP.

Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) are still at higher risk for cardiovascular diseases (CVDs) that are mediated by chronic inflammation. Identification of novel inflammatory mediators with the inherent potential to be used as CVD biomarkers and also as therapeutic targets is critically needed for better risk stratification and disease management in PLWH. Here, we investigated the expression and potential role of the multi-isoform proinflammatory cytokine IL-32 in subclinical atherosclerosis in PLWH (n=49 with subclinical atherosclerosis and n=30 without) and HIV- controls (n=25 with subclinical atherosclerosis and n=24 without). While expression of all tested IL-32 isoforms (α, β, γ, D, ϵ, and θ) was significantly higher in peripheral blood from PLWH compared to HIV- controls, IL-32D and IL-32θ isoforms were further upregulated in HIV+ individuals with coronary artery atherosclerosis compared to their counterparts without. Upregulation of these two isoforms was associated with increased plasma levels of IL-18 and IL-1β and downregulation of the atheroprotective protein TRAIL, which together composed a unique atherosclerotic inflammatory signature specific for PLWH compared to HIV- controls. Logistic regression analysis demonstrated that modulation of these inflammatory variables was independent of age, smoking, and statin treatment. Furthermore, our in vitro functional data linked IL-32 to macrophage activation and production of IL-18 and downregulation of TRAIL, a mechanism previously shown to be associated with impaired cholesterol metabolism and atherosclerosis. Finally, increased expression of IL-32 isoforms in PLWH with subclinical atherosclerosis was associated with altered gut microbiome (increased pathogenic bacteria; Rothia and Eggerthella species) and lower abundance of the gut metabolite short-chain fatty acid (SCFA) caproic acid, measured in fecal samples from the study participants. Importantly, caproic acid diminished the production of IL-32, IL-18, and IL-1β in human PBMCs in response to bacterial LPS stimulation. In conclusion, our studies identified an HIV-specific atherosclerotic inflammatory signature including specific IL-32 isoforms, which is regulated by the SCFA caproic acid and that may lead to new potential therapies to prevent CVD in ART-treated PLWH.

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