# Vascular contributions to HIV-associated Neurocognitive Disorders (HAND)

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $821,867

## Abstract

PROJECT SUMMARY/ABSTRACT:
As people with HIV (PWH) age, chronic comorbidities such as cerebrovascular disease and poorer cognition
become more prevalent. There exist a disparity in the rates of cerebrovascular disease and dementia among
PWH. Possible contributing factors include disproportionate prevalence of vascular risk factors such as
hypertension, diabetes, dyslipidemia and smoking in PWH. Additionally, the socioeconomic context of PWH
(that includes but is not limited to homophobia, structural racism and societal stigma) may translate in stressors
that may contribute to poorer vascular health. In this proposal, we attempt to fill in the knowledge gap of how
vascular risk factors and socioeconomic stressors may affect cerebrovascular disease and cognition in PWH.
We propose that soluble blood biomarkers of endothelial activation such as vascular cell adhesion molecule-1
(VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor alpha (TNFα), are key
mediators of these relationships, and more importantly, they could be therapeutic targets. In aim 1, we
hypothesize that uncontrolled vascular risk factors and socioeconomic stressors interact with HIV to relate to
increased levels of blood biomarkers of endothelial activation compared to age-, sex-, and ethnicity-matched
uninfected controls. In aim 2, we propose that disparities in HIV-related cerebrovascular disease compared to
uninfected controls are mediated by increased levels of blood biomarkers of endothelial activation. In aim 3, we
hypothesize that disparities in MRI-based neurodegeneration and cognition in PWH compared to matched
uninfected controls are mediated by increased levels of blood biomarkers of endothelial activation and MRI-
based cerebrovascular disease. To confirm the central role of endothelial activators over other inflammatory
molecules, we will carry out confirmatory analyses using five models that include LASSO without interaction
terms, Lasso with interaction terms, RF, XGBoost and Model Average. With the execution of these aims, we
will produce rigorous scientific evidence supporting the unique physiopathology of HIV-related cerebrovascular
disease and neurodegeneracion. Furthermore, by establishing endothelial activation as a key pathway in
mediating HIV-related disparities in cerebrovascular disease and neurodegeneration, we will provide
preliminary support to test whether modification of these inflammatory pathways (e.g. TNFα blockade) may
prove beneficial in PWH or in certain subgroups to be identified in this study.

## Key facts

- **NIH application ID:** 10405357
- **Project number:** 1R01AG076383-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jose Gutierrez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $821,867
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405357

## Citation

> US National Institutes of Health, RePORTER application 10405357, Vascular contributions to HIV-associated Neurocognitive Disorders (HAND) (1R01AG076383-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10405357. Licensed CC0.

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