# Imaging immune signaling in virally-suppressed HIV

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $206,806

## Abstract

PROJECT SUMMARY
This project will image the proliferation of activated microglia, resident immune cells in the brain, in virally
suppressed people with human immunodeficiency virus (VS+PWH). The proposed work builds on our prior
data that support a link between domain-specific cognitive impairment and localized, microglial activation in
VS+PWH. In order to specifically image microglia in the living brain, we developed a radiotracer, [11C]CPPC
that targets the colony stimulating factor 1 receptor (CSF1R) expressed by microglia. High CSF1R in brain has
been reported in human postmortem cases of neurodegeneration including VS+PWH. High CSF1R was also
found in frontal cortex of a simian immunodeficiency virus-infected macaque model of HIV, including virally
suppressed cases after antiretroviral therapy. Furthermore, its role in potentiating proliferation of neurotoxic
microglial response makes CSF1R an attractive target for therapeutic depletion of microglia in
neurodegenerative disease. Use of [11C]CPPC with positron emission tomography (PET) in humans is well
tolerated and allows us to localize and estimate microglial density in human brain in vivo. Based on published
evidence and our preliminary data, we hypothesize higher CSF1R, consistent with proliferation of activated
microglia, in the brains of VS+PWH compared to matched, uninfected controls (HIV-CON). Within VS+PWH, we
hypothesize that higher regional CSF1R will be associated with lower cognitive performance, with the affected
cognitive domains shaped by the regional pattern of high CSF1R. We therefore propose to use [11C]CPPC
PET cross-sectionally in VS+PWH and HIV-CON to assess group differences in the CSF1R that marks
microglial activation and proliferation. We will also assess relationships between regional CSF1R and cognitive
performance. In summary, early detection of pathological microglial activity that is linked to neuropsychological
impairment remains an unmet medical need, and CSF1R is a compelling microglial target for both imaging and
therapy. Our study will provide preliminary data toward design of a larger scale proposal to study further the
role of CSF1R signaling in cognitive impairment within VS+PWH. Furthermore, it may establish CPPC PET as
a promising tool for studies aimed at monitoring localized microglial response in VS+PWH over aging and in
response to neuroimmune therapy.

## Key facts

- **NIH application ID:** 10260649
- **Project number:** 5R21MH125278-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jennifer Marie Coughlin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $206,806
- **Award type:** 5
- **Project period:** 2020-09-10 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260649

## Citation

> US National Institutes of Health, RePORTER application 10260649, Imaging immune signaling in virally-suppressed HIV (5R21MH125278-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10260649. Licensed CC0.

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