# Antiretroviral Therapy Impacts Autophagy in Astrocytes, and May Contribute to HIV Associated Neurocognitive Disorders

> **NIH NIH K08** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $194,400

## Abstract

Project Summary/Abstract
This proposal presents a 4 year research career development program focused on the study of
macroautophagy (autophagy) in the context of HIV associated neurocognitive disorders (HAND) to increase
the understanding of HAND pathogenesis with the goal of identifying targets for treatment of HAND. The
candidate is currently an Instructor of Infectious Diseases and of Pathology at Montefiore Medical
Center/Albert Einstein College of Medicine. The proposal builds on the candidate’s previous HIV research and
clinical experiences by integrating two new domains of expertise, overseen by her mentors, Dr. Berman and
Dr. Cuervo. The proposed experiments and didactic work will provide Dr. Cheney with the skill sets to enable
her transition to independence as a Principal Investigator at the crossroads of neuroHIV and macroautophagy.
A significant number of people with HIV (PWH) develop HAND despite control of viremia with antiretroviral
therapy (ART). Efforts to treat HAND are hindered by an incomplete understanding of the factors underlying its
development. Data suggest that dysregulated autophagy may contribute to HAND, but much remains to be
understood, specifically in astrocytes. It is essential to maintain astrocyte homeostasis because they are major
support cells of the brain, performing many vital functions for the CNS. As astrocytes rely on autophagy for
homeostasis, it is particularly important to understand dysregulated astrocyte autophagy as it may contribute to
HAND. The foundation for this proposal is based on our published data demonstrating an inhibitory effect on
autophagy in primary human astrocytes resulting from treatment with a commonly prescribed regimen of
Tenofovir, Emtricitabine and Raltegravir (ART). The aims of this proposal are to: 1. Characterize ART induced
changes in autophagy in human astrocytes, 2. Characterize selective autophagy in human astrocytes treated
with ART, and 3. Define changes in astrocyte-specific functions as a result of ART treatment, and correlate
with changes in autophagy. These aims will expand the understanding of HAND development in PWH in the
ART era, with the ultimate objective of identifying therapeutic targets with which to mitigate HAND.

## Key facts

- **NIH application ID:** 10899683
- **Project number:** 5K08MH130210-03
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Laura Cheney
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,400
- **Award type:** 5
- **Project period:** 2022-08-18 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899683

## Citation

> US National Institutes of Health, RePORTER application 10899683, Antiretroviral Therapy Impacts Autophagy in Astrocytes, and May Contribute to HIV Associated Neurocognitive Disorders (5K08MH130210-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10899683. Licensed CC0.

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