# Viral and Host Determinants of Cognitive Status in Vertically Transmitted HIV

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-ST. LOUIS · 2021 · $645,454

## Abstract

PROJECT SUMMARY-ABSTRACT
The purpose of the proposed study is conduct a controlled investigation of HIV host and viral dynamics
on brain integrity in vertically infected children on stable combined antiretroviral therapy (cART) in
Myanmar. Outcomes from the PREDICT trial in Southeast Asia revealed residual cognitive impairment
among pediatric HIV+ individuals with vertical infection. Socioeconomic variables predicted cognitive test
performance among infected children and children exposed to HIV but uninfected with the virus. Efforts
to define the neuropathogenesis of HIV require adequate control of these environmental variables
known to influence cognitive test performance and engagement in ADLs. The majority of HIV+ children
in Myanmar reside in privately funded orphanages with standardized caregiver status, nutrition, and
education. Our preliminary work reveals cognitive impairment in these children on cART with high CD4
count when compared to demographically matched healthy controls (HIV-). Further, 40% of the HIV+
children express preferential use of the CXCR4 co-receptor and the degree of cognitive impairment is
greater among these children compared to those expressing the CCR5 co-receptor despite similar CD4
counts. Previous studies have associated CXCR4 utilization with worse cognition in HIV+ adults with
advanced disease, but it is unclear from these studies if co-receptor subtype is liked to cognitive
impairment or more simply a correlated variable between disease severity and cognitive impairment. Our
preliminary data suggests a mechanistic role for CXCR4 on reduced brain integrity independent of
advanced disease, emphasizing the need to identify the relevant immunological factors. Work from our
team previously demonstrated that circulating monocyte HIV content, monocyte subpopulations, and
myeloid-derived immunological mediators are key mechanisms of HIV-associated neurocognitive
impairment. The present study will examine these immunological mechanisms and co-receptor tropism
in the cascade of events related to cognitive impairment in vertically infected youth. This information is
critical to facilitate the development of targeted treatments to improve cognitive function among children
with vertically infected HIV. We will enroll 120 HIV+ vertically infected children and adolescents
between the ages of 8 and 15 and 60 HIV- controls matched for demographics, and all residing in
privately funded orphanages. Neuropsychological, virological, and immunological assays will be completed
to determine pediatric HIV neuropathogenesis in the context of stable cART.

## Key facts

- **NIH application ID:** 10074595
- **Project number:** 5R01MH108559-05
- **Recipient organization:** UNIVERSITY OF MISSOURI-ST. LOUIS
- **Principal Investigator:** Robert Harris Paul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $645,454
- **Award type:** 5
- **Project period:** 2016-12-22 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074595

## Citation

> US National Institutes of Health, RePORTER application 10074595, Viral and Host Determinants of Cognitive Status in Vertically Transmitted HIV (5R01MH108559-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074595. Licensed CC0.

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