# Aging, Polypharmacy and Neurotoxicity in Adults Living with HIV

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $832,882

## Abstract

ABSTRACT
Central nervous system (CNS) complications continue to occur among adults aging with HIV. For example,
neurocognitive impairment occurs in 30-50% of persons with HIV (PWH). With advancing age, cognitive and
mood disorders such as depression increase in frequency and in severity. While research to date has focused
on the biological mechanisms associated with the aging of the CNS (e.g., amyloid-related pathology), few studies
have focused on aging and prescribed, potentially neurotoxic drugs influence the effects of HIV and antiretroviral
therapy (ART) on cognition and depression. Studies of neurotoxicity of ART drugs and prescribed drugs in older
PWH have largely been limited by small sample sizes, suboptimal neurocognitive characterization, and relatively
short follow-up. This proposal will address these limitations by using data and specimens from nearly 20,000
comprehensive medical and neurobehavioral assessments collected over more than 20 years. CNS
complications, such as neurocognitive impairment and major depression disorder, are a key area for
multidisciplinary studies of HIV and aging in order to characterize the interactions between HIV, comorbid
diseases, and their treatment and to gain insights into the pathogenesis of these complications that may inform
therapeutics. The overarching hypothesis is that prescribed drug-related neurotoxicity increasingly contributes
to the incidence and persistence of CNS complications in PWH as they age. To address this, the proposed
project is organized into three aims: 1) Determine how age and concomitantly prescribed drugs modify the
relationships between ART drugs and neurocognitive performance or depression using a longitudinal database
of more than 20,000 comprehensive assessments and advanced analytical methods; 2) Determine how age and
concomitantly prescribed drugs modify the dose-effect relationships between ART drugs and NC performance
and depression using physiologically-based pharmacokinetic modeling; and 3) Explore the mechanisms by
which concomitant drugs modify ART neurotoxicity using a novel high-throughput, inducible human pluripotent
stem cell culture method and extracellular vesicle characterization. The completion of this proposal will provide
valuable data on how aging interacts with prescribed drugs to increase the risk of ART neurotoxicity and CNS
complications. The results may also inform future interventions to prevent and treat CNS complications in older
PWH.

## Key facts

- **NIH application ID:** 10149896
- **Project number:** 5R01AG063659-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Scott L Letendre
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $832,882
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149896

## Citation

> US National Institutes of Health, RePORTER application 10149896, Aging, Polypharmacy and Neurotoxicity in Adults Living with HIV (5R01AG063659-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10149896. Licensed CC0.

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