# Functional impact of antiretroviral drugs on human neuronal subtypes

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2020 · $202,500

## Abstract

PROJECT SUMMARY
Antiretroviral therapy (ART) has proven remarkably successful in decreasing the viral load in HIV-infected
individuals but there are potential off-target effects that can result in the emergence of neurocognitive
impairments and/or psychiatric symptoms. To better predict which individuals may be susceptible to side
effects, we need a better mechanistic understanding of how ART drugs may be affecting the human central
nervous system. Although animal models and postmortem analyses provide critical information, additional
complementary approaches are needed to bridge the gap between these models and identify biomarkers and
cellular signatures of ART. Recently, the introduction of methodology to generate human induced pluripotent
stem cells (iSPCs) allows for the generation of a renewable resource of any cell type in human body. For
neurological and psychiatric disorders in particular, this approach holds the promise of facilitating controlled
investigations using human neurons to understand how genetic and environmental perturbations may alter
cellular function and trigger widespread pathology in neural circuits. This project is designed to evaluate the
molecular, cellular, and functional impact of several ART drugs on different subtypes of human neurons. We
will use a combination of approaches to generate a comprehensive profile of the effects of these drugs at the
single cell level in both cortical glutamatergic neurons and GABAergic neurons. Successful completion of these
experiments will generate single cell transcriptomic and epigenomic datasets for the research community and
could lead to the identification of cell-type specific novel pathways and targets of ART drugs. This platform will
also provide a foundation to investigate individual variability in response to ART drugs and a potential
diagnostic tool to guide treatment decisions.

## Key facts

- **NIH application ID:** 10025266
- **Project number:** 5R21MH122239-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Kimberly Christian
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $202,500
- **Award type:** 5
- **Project period:** 2019-09-26 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025266

## Citation

> US National Institutes of Health, RePORTER application 10025266, Functional impact of antiretroviral drugs on human neuronal subtypes (5R21MH122239-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10025266. Licensed CC0.

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