# The role of antidepressants in central and peripheral myeloid HIV persistence and inflammation

> **NIH NIH K01** · DREXEL UNIVERSITY · 2024 · $185,220

## Abstract

Project Summary/Abstract
This is a resubmission application for a Mentored Research Scientist Development Award (K01) to support the
career development of Dr. Stephanie Matt to facilitate her transition to an independent academic investigator in
the HIV and neuroimmunology research fields. An intense and comprehensive mentoring and research plan has
been developed to use high-throughput techniques to assess antidepressant-mediated HIV viral dynamics and
inflammatory signaling in human myeloid and co-culture models. Dr. Matt’s training will be supported by a firm
institutional commitment to her career development and a strong mentoring team of leaders in the HIV and
psychoneuroimmunology research fields, each providing strategic guidance in both the development of this
proposal and mentoring as her career progresses. The proposed research plan is a natural extension of the
recent studies Dr. Matt has been conducting in her mentor Dr. Peter Gaskill’s laboratory but is distinguished by
examination of HIV infection and inflammation in clinical cohorts, biostatistical analyses, as well as neuronal
profiling. Neurological complications of HIV infection (neuroHIV) remain prevalent even with antiretroviral therapy
(ART). Depression is one of these increasingly common complications that can substantively worsen HIV
disease progression. Myeloid cells such as macrophages and microglia are primary HIV targets that can serve
as viral reservoirs and drive HIV neuropathogenesis, but their activation also mediates depression-associated
inflammation. Inflammatory links between HIV, depression, and the drugs used to treat them are not well
understood. However, HIV, depression, and antidepressants act on receptors and transporters that alter
neurotransmission, and neurotransmitter receptor activity on immune cells can influence inflammatory signaling
and HIV infection. This suggests that changes in neurotransmitter levels by antidepressants could affect the size
of myeloid HIV reservoirs, exacerbating neuroHIV and influencing the progression of depression and treatment
resistance. Thus, the overarching hypothesis of this proposal is that specific antidepressants can
activate both CNS and peripheral myeloid cells that critically contribute to inflammation and HIV
persistence. This proposal will test this hypothesis using a multifaceted approach to evaluate the effects of in
vivo antidepressants and ART on viral dynamics and inflammation in myeloid cells in association with cognitive
function in depressed people living with HIV (Aim 1), effects of antidepressants regulating discrete viral dynamics
in HIV-infected, ART-treated iPSC CNS and peripheral myeloid populations (Aim 2), and how antidepressants
influence viral dynamics and neuronal function in co-cultures of HIV-infected, ART-treated microglia and distinct
neuronal subtypes (Aim 3). These studies will significantly advance our understanding of the cellular
mechanisms underlying the role of antidepressants in H...

## Key facts

- **NIH application ID:** 10841716
- **Project number:** 5K01MH132466-02
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Stephanie Marie Matt
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $185,220
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841716

## Citation

> US National Institutes of Health, RePORTER application 10841716, The role of antidepressants in central and peripheral myeloid HIV persistence and inflammation (5K01MH132466-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10841716. Licensed CC0.

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