# COCAINE USE AND HIV ANTIRETROVIRAL THERAPY EFFICACY IN THE CNS

> **NIH NIH R00** · JOHNS HOPKINS UNIVERSITY · 2020 · $81,875

## Abstract

Project Summary/Abstract
Human immunodeficiency virus-1 (HIV) enters the central nervous system (CNS) early after primary infection
and results in a spectrum of cognitive deficits, collectively termed HIV associated neurocognitive disorders
(HAND). While successful in reducing peripheral viral loads to undetectable levels, antiretroviral therapy (ART)
does not effectively quell CNS viremia to the same extent. As a result, ART has not decreased the prevalence
of HAND, which continues to increase as the life expectancy for seropositive individuals rises. HIV-infected
substance abusers exhibit more severe cognitive impairment compared with their non-drug abusing
counterparts. Specifically, cocaine use is associated with an accelerated incidence and progression of HAND.
This occurs, in part, due to cocaine-mediated increases in HIV replication and resultant blood-brain barrier
perturbations, alterations in ART metabolism, and neuroinflammatory responses that contribute to the
sequelae characteristic of HAND. To understand more fully the impact of cocaine use on the pathogenesis of
HAND, I will examine two major mechanisms by which cocaine may interfere with ART effectiveness in the
CNS. I will evaluate the transport of ART across the blood-brain barrier in the context of cocaine, focusing on
the expression and function of influx and efflux transporters. Additionally, I will characterize the association
between polymorphisms in cytochrome P450 drug metabolizing enzymes and HAND in HIV-infected
individuals who currently consume illicit substances, as well as those without current substance abuse.

## Key facts

- **NIH application ID:** 10155978
- **Project number:** 3R00DA044838-04S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Dionna Whitney Williams
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $81,875
- **Award type:** 3
- **Project period:** 2019-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155978

## Citation

> US National Institutes of Health, RePORTER application 10155978, COCAINE USE AND HIV ANTIRETROVIRAL THERAPY EFFICACY IN THE CNS (3R00DA044838-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10155978. Licensed CC0.

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