# Dopamine D1-like receptor stimulation promotes HIV neuroimmune pathogenesis in iPSC-derived human cortical assembloids

> **NIH DA F30** · DREXEL UNIVERSITY · 2026 · $50,196

## Abstract

Neurologic complications remain prevalent in nearly 50% of people with HIV (PWH) and persist despite viral
suppression with antiretroviral therapy (ART). Though the exact processes mediating HIV neuropathogenesis
are not well understood, co-morbidities such as substance use disorders (SUD), which are higher in PWH
compared to the general population, exacerbate neuropathogenesis of HIV and worsen outcomes. Multiple
substances of misuse are reported to increase HIV replication, induce inflammatory signaling, and amplify
neurodegenerative phenotypes. Thus, there is a significant need to understand the intersection between SUD
and NeuroHIV to improve longitudinal care and inform the public.
The overlapping effects of distinct substances of misuse on HIV pathogenesis in the CNS suggest that a common
pathway may be involved through presently undefined mechanisms. All addictive substances increase
extracellular dopamine in the central nervous system (CNS), which signals neurons and other nearby glial cells
expressing dopamine receptors. Our lab has shown that myeloid cells such as macrophages and microglia,
which are major HIV reservoirs in the brain, express dopamine receptors more D1-like receptors (D1 and D5)
than D2-like receptors (D2, D3, D4). Treatment of macrophages and microglia with micromolar concentrations
of dopamine increased pro-inflammatory signaling, increased viral entry, and potentiated viral secretion in vitro.
We recently found that a higher D1-like to D2-like ratio is associated with a more pro-inflammatory response in
microglia. Further, we showed that dopamine increases activation of nuclear factor-kappa B (NF-κB) in
macrophages, and that inhibition of NF-κB can block the pro-inflammatory effects of dopamine. Together, these
data suggest that dopamine-enriched brain regions, such as the cortex and striatum, may be especially
vulnerable to HIV and neuroinflammation in PWH and co-morbid addiction through the action of dopamine on
microglia. Therefore, 

## Key facts

- **NIH application ID:** 11257085
- **Project number:** 1F30DA064444-01
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Yash Dinesh Agarwal
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** DA
- **Fiscal year:** 2026
- **Award amount:** $50,196
- **Award type:** 1
- **Project period:** 2026-02-27T00:00:00 → 2030-02-26T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11257085

## Citation

> US National Institutes of Health, RePORTER application 11257085, Dopamine D1-like receptor stimulation promotes HIV neuroimmune pathogenesis in iPSC-derived human cortical assembloids (1F30DA064444-01). Retrieved via AI Analytics 2026-07-10 from https://api.ai-analytics.org/grant/nih/11257085. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*