# Understanding the cellular basis for persistent immune activation in the central nervous system during virologically suppressed HIV

> **NIH NIH K23** · YALE UNIVERSITY · 2021 · $194,794

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite major advances in combination antiretroviral therapy (ART), adults living with HIV infection continue to
suffer from high rates of morbidities associated with chronic immune activation, including neurocognitive
impairment. Indeed, the prevalence of neurocognitive disorders in adults with HIV remains unchanged in the
ART era: an estimated 50% of adults with virologically suppressed HIV have some form of neurocognitive
impairment. Understanding the cellular basis for persistent CNS immune activation is thus critical for reducing
neurological morbidities in the growing population of adults with HIV on treatment. Studies to date have
focused on CSF biomarkers or CSF immune cell flow cytometry, but these studies are limited by the need to
pre-specify markers of interest, thus missing the opportunity to identify de novo cell populations that may drive
CNS immune activation and downstream neuronal damage, including rare myeloid subsets.
The candidate has developed a reliable pipeline to profile single cerebrospinal fluid (CSF) immune cells at the
transcriptional level, and has successfully used this technique to identify a rare cellular subset in CSF that
presents a gene expression pattern consistent with disease-associated microglia. The research proposed here
will utilize these state of the art methods to analyze CSF and blood from adult volunteers with and without HIV
disease, to characterize novel or rare cell populations in the CNS during treated, suppressed HIV. Defining
CNS immune activation in exquisite detail, including cellular populations that distinguish HIV infection during
ART, has the potential to provide critical targets for therapeutic intervention for residual neurologic impairment
during HIV treatment.
The principal investigator is a physician scientist, with specialized training in Neuroinfectious disease and a
PhD in Neurogenetics. Her career goal is to become an independent investigator studying neurological
sequelae of infectious diseases, with a special focus on neurological effects of HIV infection. The proposed
K23 training plan will provide the candidate with mentorship and coursework to build specific expertise
necessary to execute the proposed project and become independent in her field, including expertise in: 1.
Immunology and Neuro-infectious diseases 2. “Big data” genomics and associated computational analysis, and
3. Skills necessary to head an independent, patient-oriented research program. To achieve these goals, Dr.
Farhadian has assembled a primary mentoring team consisting of experts in Neuro-HIV, Neuroimmunology,
and Bioinformatics.

## Key facts

- **NIH application ID:** 10236380
- **Project number:** 5K23MH118999-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Shelli Farhadian
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,794
- **Award type:** 5
- **Project period:** 2018-09-25 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236380

## Citation

> US National Institutes of Health, RePORTER application 10236380, Understanding the cellular basis for persistent immune activation in the central nervous system during virologically suppressed HIV (5K23MH118999-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10236380. Licensed CC0.

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