Background People with HIV (PWH) have subclinical coronary artery disease (CAD) despite low traditional atherosclerotic cardiovascular disease (ASCVD) risk scores. Coronary plaque in PWH presents as a unique phenotype, but little is known about the contributions of specific inflammatory pathways to plaque phenotypes in PWH. Methods The REPRIEVE Mechanistic Substudy enrolled PWH on ART without known cardiovascular disease. We used a targeted discovery proteomics approach to evaluate 246 unique proteins representing cardiovascular, inflammatory and immune pathways. Proteomic signatures were determined for presence of coronary artery calcium (CAC > 0) and presence of coronary plaque. Results Data were available for 662 participants [51 ± 6 years, ASCVD risk score 4.9%±3.1%]. Among 12 proteins associated with both CAC and presence of coronary plaque, independent of ASCVD risk score, the ORs were highest for NRP1 [5.1(95% CI 2.3-11.4) for CAC and 2.9(95% CI 1.4-6.1) for presence of plaque]. Proteins uniquely related to presence of plaque were CST3, LTBR, MEPE, PLC, SERPINA5, and TNFSF13B; in contrast, DCN, IL-6RA, OSMR, ST2 and VCAM1 were only related to CAC. Conclusions Distinct immune and inflammatory pathways are differentially associated with subclinical CAD phenotypes among PWH. This comprehensive set of targets should be further investigated to reduce atherosclerosis and ASCVD in PWH.

Objectives To compare the use of coronary computed tomography angiography (CCTA) between academic and non-academic sites across Europe over the last decade. Methods We analyzed a large multicenter registry (ESCR MR/CT Registry) of stable symptomatic patients who received CCTA 01/2010-01/2020 at 47 (22%) academic and 165 (78%) non-academic sites across 19 European countries. We compared image quality, radiation dose, contrast-media-related adverse events, patient characteristics, CCTA findings, and downstream testing between academic and non-academic sites. Results Among 64,317 included patients (41% female; 60 ± 13 years), academic sites accounted for most cases in 2010-2014 (52%), while non-academic sites dominated in 2015-2020 (71%). Despite less contemporary technology, non-academic sites maintained low radiation doses (4.76 [2.46-6.85] mSv) with a 30% decline of high-dose scans ( > 7 mSv) over time. Academic and non-academic sites both reported diagnostic image quality in 98% of cases and low rate of scan-related adverse events (0.4%). Academic and non-academic sites examined similar patient populations (41% females both; age: 61 ± 14 vs. 60 ± 12 years; pretest probability for obstructive CAD: low 21% vs. 23%, intermediate 73% vs. 72%, high 6% both, CAD prevalence on CCTA: 40% vs. 41%). Nevertheless, non-academic sites referred more patients to non-invasive ischemia testing (6.5% vs. 4.2%) and invasive coronary angiography/surgery (8.5% vs. 5.6%). Conclusions Non-academic and academic sites provide safe, high-quality CCTA across Europe, essential to successfully implement the recently updated guidelines for the diagnosis and management of chronic coronary syndromes. However, despite examining similar populations with comparable CAD prevalence, non-academic sites tend to refer more patients to downstream testing. Key Points• Smaller non-academic providers increasingly use CCTA to rule out obstructive coronary artery disease.• Non-academic and academic sites provide comparably safe, high-quality CCTA across Europe.• Compared to academic sites, non-academic sites tend to refer more patients to downstream testing.

Background August Among people with HIV (PWH), sex-differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein. Methods REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)-treated PWH. At entry, a subset of U.S. participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (N = 755 CTA; N = 725 CTA + immune). We characterized sex-differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score. Results The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median 4.9% vs. 2.1%), while obesity rates were higher among females (48% vs. 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors [RR(95% CI) for any plaque 0.67 (0.50, 0.92); RR for NC/V-P 0.71 (0.51, 1.00) (adjusted for ASCVD risk score and BMI)]. Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P < 0.001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P < 0.02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = 0.055). Conclusions Among U.S. PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer, but not other tested parameters. Previous Presentation Conference on Retroviruses and Opportunistic Infections (CROI), 2022; International Workshop on HIV and Women (IWHW), 2022; AIDS Clinical Trials Group Network Meeting, 2022; REPIREVE State of the Science Meeting, 2022. ClinicalTrials.gov Identifier NCT0234429 (date of initial registration: January 22, 2015)