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

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.