# Myelin Content and Cognitive Trajectories in Young Adults Living with Virally Suppressed HIV

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $585,425

## Abstract

Project Summary/Abstract
With the introduction of antiretroviral therapy (ART), the prevalence of severe manifestations of HIV-associated
neurocognitive disorders has improved over the past few decades. However, in the context of viral
suppression, new pressing questions have emerged regarding the etiology of the persistent cognitive sequalae
in PLWH on ART. Up to 40% of individuals living with virally suppressed HIV experience cognitive impairment
and the mechanisms underlying neurologic injury in these individuals remain poorly understood. A hallmark
finding of HIV associated neurocognitive disorder (HAND), white matter injury, has primarily been evaluated
indirectly through non-specific markers of myelination on neuroimaging in PLWH or pathologic markers in
animal studies. Our team has developed an MRI sequence, myelin water imaging, to directly measure myelin
content, a component of white matter, in vivo. We will apply this novel sequence to longitudinally evaluate if
reduced myelination rates occur in young adults living with virally suppressed HIV (YLWH) compared to
demographic and antiretroviral therapy risk factor matched, HIV-uninfected controls. Additionally, we will
evaluate the independent correlation between changes in myelin content and cognitive trajectories, accounting
for social determinants of health, to determine if loss of myelin may contribute to the development of cognitive
disorders in YLWH. The premise of this application is based on our preliminary data, which demonstrate
decreased global and regional myelin content in young adults living with virally suppressed HIV compared to
age and sex matched HIV-uninfected controls and that myelin loss mediates the relationship between immune
activation and lower domain specific cognitive scores in young adults living with virally suppressed HIV. We will
combine our novel imaging methodology assessing myelin content with established imaging techniques, such
as diffusion tensor imaging, longitudinally acquired cognitive data and standardized measures of social
determinants of health to determine predictors of the latent cognitive phenotypes within our cohort of virally
suppressed YLWH using an unbiased statistical modeling approach, group-based trajectory analyses. The
information provided by our proposed study will not only improve our understanding of changes in myelin
content in YLWH in relation to cognitive outcomes, but also provide the basis for evaluating myelin water
imaging as a biomarker to identify PLWH of all ages at risk for cognitive impairment. This work may provide the
preliminary data needed to support early intervention trials of myelin preservation or remyelination therapies to
improve cognition in a broader population of PLWH.

## Key facts

- **NIH application ID:** 10850803
- **Project number:** 5R01MH134663-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Payal Patel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $585,425
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850803

## Citation

> US National Institutes of Health, RePORTER application 10850803, Myelin Content and Cognitive Trajectories in Young Adults Living with Virally Suppressed HIV (5R01MH134663-02). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10850803. Licensed CC0.

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