Soluble Indicators of Endothelial Injury and Activation Emerge During Acute HIV Infection and Persist Despite Rapid Antiretroviral Therapy Initiation

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ID: 332280
2026
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Abstract
BACKGROUND: Vascular activation occurs during human immunodeficiency virus (HIV) infection and is a risk factor for cardiovascular disease (CVD). This study investigates whether vascular endothelial and hemostatic perturbations emerge during acute HIV infection (AHI) and persist despite immediate antiretroviral therapy (ART) initiation. METHODS: Thirteen plasma biomarkers indicative of endothelial and hemostatic perturbations were measured in 83 RV254 AHI cohort participants during pre-ART AHI and at week 288 post-ART, compared with cross-sectional measures from 32 people without HIV (PWoH). Hierarchical clustering was applied to week 288 biomarker profiles of RV254 participants and PWoH to identify distinct biomarker phenotypes. RESULTS: During pre-ART AHI, RV254 participants exhibited higher intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tissue factor, neopterin, and myeloperoxidase than PWoH (P < .05), independent of age, sex, and body mass index (BMI). These markers correlated with plasma HIV RNA or the CD4/CD8 ratio (P < .05). At week 288, significant reductions in ICAM-1, VCAM-1, vascular endothelial growth factor (VEGF)-C, VEGF-D, neopterin, and myeloperoxidase and a significant increase in tissue plasminogen activator were observed in RV254 (P < .05). However, VCAM-1 and thrombomodulin remained higher, and VEGF-A remained lower in RV254 participants compared to PWoH (P < .05). Hierarchical clustering identified 2 distinct clusters. Despite comparable 10-year CVD risk, 1 cluster exhibited concomitant elevation of ICAM-1, ICAM-2, VCAM-1, and E-selectin. Notably, 45% of RV254 participants vs 13% of PWoH were classified into this phenotype. CONCLUSIONS: Endothelial and hemostatic perturbations emerge during AHI and correlate with HIV-related parameters. Despite suppressive ART, RV254 participants remained approximately 3.5 times more likely than PWoH to exhibit an endothelial activation biomarker phenotype.
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Authors Phillip Chan, Kirati Tayutivutikul, Bonnie M. Slike, Suteeraporn Pinyakorn, Kathryn B. Holroyd, Carlo Sacdalan, Lily Metzger, Pathariya Promsena, Eugene Kroon, D Colby, Somchai Sriplienchan, Nittaya Phanuphak, Robert Paul, Victor Valcour, Lishomwa C. Ndhlovu, Lydie Trautmann, Shelly J. Krebs, Serena Spudich
Journal The Journal of infectious diseases
Year 2026
DOI
10.1093/infdis/jiag495
URL
https://doi.org/10.1093/infdis/jiag495
Keywords Keywords not found

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