CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

842

Multiomics Profiles of SHBG Are Associated With Subclinical Atherosclerosis in Men With HIV Yi Wang 1 , Wendy Post 2 , Howard Hodis 3 , Zheng Wang 1 , Mallory Witt 4 , Todd Brown 5 , Mark Kuniholm 6 , Patrick Caron 7 , Clary B. Clish 8 , Chantal Guillemette 7 , Robert D. Burk 1 , Robert C. Kaplan 1 , Qibin Qi 1 , David B. Hanna 1 , Brandilyn A. Peters 1 1 Albert Einstein College of Medicine, Bronx, NY, USA, 2 The Johns Hopkins University, Baltimore, MD, USA, 3 University of Southern California, Los Angeles, CA, USA, 4 University of California Los Angeles, Los Angeles, CA, USA, 5 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 6 State University of New York at Albany, Rensselaer, NY, USA, 7 Centre Hospitalier Universitaire de Québec Université Laval, Quebec, Canada, 8 Broad Institute of MIT and Harvard, Cambridge, MA, USA Background: Sex hormones and HIV infection both influence cardiovascular health. However, the relationship between sex hormones and subclinical atherosclerosis is not fully understood, especially in the context of HIV. Methods: Among 321 men (65% with HIV) from the MACS/WIHS Combined Cohort Study, we measured 14 serum sex hormones and sex hormone-binding globulin (SHBG), assessed carotid artery plaque using B-mode ultrasound, and performed shotgun metagenomic sequencing on stool samples. In 312 men, we measured 986 plasma metabolites via liquid chromatography-tandem mass spectrometry and 2883 plasma proteins using the Olink Explore 3072 platform. Separately in men with and without HIV (MWH, MWOH) and with adjustment for covariates, we (1) examined associations of sex hormones with plaque; (2) characterized multi-omics profiles related to sex hormones; and (3) explored whether identified multi-omics signatures mediate the relationship between sex hormones and plaque (Fig. 1a). Results: Mean age was 63.0±7.4 years, and 31.5% had carotid artery plaque. Sex hormones were differentially associated with plaque in MWH and MWOH. In MWH, SHBG was associated with lower odds of plaque (OR=0.60, 95% CI: 0.41, 0.90), overall gut microbial composition, lower abundance of species from Prevotella , Fibrobacter and Coprococcus , higher levels of certain metabolites (mainly lipid and carnitine metabolites) and proteins enriched in the cell-cell adhesion pathway. Some SHBG-related species (e.g., Mediterranea massiliensis ), metabolites (e.g., Hex2Cer 42:2;O2) and proteins (e.g., enriched in immune response) were also associated with plaque in MWH. We then generated SHBG related microbiome, metabolite and protein scores via linear combination of related species, metabolites and proteins, respectively. All SHBG-related -omics scores were inter-correlated and inversely associated with plaque in MWH (Fig. 1b). Mediation analysis suggested that the metabolite and protein scores, but not the microbiome score, could mediate the protective association of SHBG with plaque (mediated proportions: 43.2% and 39.0%). In MWOH, estrone sulfate was positively associated with plaque (OR=3.80, 95% CI: 1.41, 10.22) but not with any species, metabolites or proteins. Conclusions: Higher SHBG was associated with lower odds of carotid artery plaque in MWH, possibly explained by alterations in lipid metabolites and proteins involved in immune response and cell function regulation. SHBG may play a protective role in cardiovascular disease in MWH.

alterations may lead to host inflammation and changes in metabolomics profiles affecting atherosclerosis is not fully elucidated, especially in the context of HIV. Methods: We examined associations of gut microbial species and functional components measured by shotgun metagenomics with carotid artery plaque (focal intima-media thickness >1.5 mm) assessed by B-mode carotid artery ultrasound in 359 men (65% HIV+, mean age 63) from the MACS/WIHS Combined Cohort Study. We measured 822 plasma metabolites using liquid chromatography-tandem mass spectrometry and 2866 circulating proteins by Olink platform. We further integrated plaque-associated microbial features with proteomics and metabolomics profiles in relation to plaque. Results: Carotid artery plaque was detected in 115 of 359 men (32%). The gut microbial species Adlercreutzia equolifaciens and Eubacterium sp3131 were associated with lower odds of plaque, while the potentially pathogenic bacterium Coprococcus sp13142 was positively associated with plaque, after adjusting for demographic and behavioral factors. Results were consistent in both men with and without HIV. We examined correlations between these plaque-associated species and conventional CVD risk factors, and found that A. equolifaciens correlated with HDL cholesterol (r=0.26, P<0.001) and inversely correlated with systolic blood pressure (r=-0.17, P=0.009). These plaque associated microbial species were also associated with a range of circulating metabolites and inflammatory proteins. For example, A. equolifaciens correlated with metabolites palmitoyl-EA (known for antihypertensive and anti-inflammatory properties) and mesobilirubinogen (a metabolic product of bilirubin with antioxidant properties), and inversely correlated with the pro-inflammatory chemokines CXCL9, immune regulator CD160 and IL-24, which promotes cell apoptosis. Associations between bacterial species and plaque were attenuated after further adjustment for specific microbial associated circulating metabolites and proteomic inflammatory markers. Conclusions: We identified gut microbial features associated with carotid artery atherosclerosis, with certain microbiota-related metabolites and inflammatory markers partially explaining these associations. This work, if validated, suggests potential gut microbiota-related targets for cardiovascular prevention in men with and without HIV.

Poster Abstracts

844

PLHIV Exhibit a COVID-19 Independent Increase of Cardiovascular Mortality in Brazil, 2019-2023 Rodrigo Moreira 1 , Valdilea Gonçalves Veloso 1 , Beatriz Grinsztejn 1 , Antonio G. Pacheco 2 1 Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil, 2 Oswaldo Cruz Institute – Fiocruz, Rio de Janeiro, Brazil Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among PLHIV. The COVID-19 pandemic exacerbated existing health disparities, particularly affecting vulnerable populations. This study aims to investigate the impact of the COVID-19 pandemic on death rates due to CVD in Brazil. Methods: All data were sourced from Brazilian Mortality Information System (SIM) from 2018 to 2023 through the DATASUS open-access database. Population

843

Multiomics Analysis of Gut Microbiome and Carotid Artery Atherosclerosis in Men With and Without HIV

Zheng Wang 1 , Yi Wang 1 , Brandilyn A. Peters 1 , Wendy Post 2 , Todd Brown 3 , Frank Palella 4 , Mallory Witt 5 , Mark Kuniholm 6 , Natalie Chichetto 7 , Robert D. Burk 1 , Kathryn Anastos 1 , Howard Hodis 8 , Robert C. Kaplan 1 , Qibin Qi 1 , David B. Hanna 1 1 Albert Einstein College of Medicine, Bronx, NY, USA, 2 The Johns Hopkins University, Baltimore, MD, USA, 3 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 Northwestern University, Chicago, IL, USA, 5 University of California Los Angeles, Los Angeles, CA, USA, 6 State University of New York at Albany, Rensselaer, NY, USA, 7 University of Florida, Gainesville, FL, USA, 8 University of Southern California, Los Angeles, CA, USA Background: Alterations in gut microbiota have been implicated in HIV infection and cardiovascular disease (CVD). However, how gut microbial

CROI 2025 256