# COCAINE USE AND HIV ANTIRETROVIRAL THERAPY EFFICACY IN THE CNS

> **NIH NIH R00** · JOHNS HOPKINS UNIVERSITY · 2020 · $244,152

## 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, neuroinflammatory responses, and neuronal damage 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 three major mechanisms by which cocaine may interfere with ART effectiveness in the CNS. In
Aim 1, I will evaluate the impact of cocaine on ART metabolism by HIV infected macrophages/microglia. These
analyses will occur during the K99 phase. Aim 2 will also be performed during the K99 phase, where I will
determine the distribution of ART in the brain during comorbid HIV infection and cocaine use by mass
spectrometric imaging. In the R00 phase of the award, I will characterize the association between
polymorphisms in drug metabolizing enzymes and HAND during Aim 3. Finally, Aim 4 will be performed in the
remainder of the R00 phase where I will evaluate the transport of ART across the BBB in the context of
cocaine. My past experience with the blood-brain barrier, HAND, and substance abuse will be combined with
my current training in CNS-specific innate immune responses and the molecular biology of HIV pathogenesis.
However, I require additional training in pharmacology of ART, mass spectrometric modalities, and
pharmacogenetics. The institutional resources and outstanding mentorship available at the Johns Hopkins
University provide a supportive and rich training environment in which to develop an independent research
program. In the K99 phase, I will receive mentorship from a team of distinguished leaders in their respective
fields: Drs. Clements, Bumpus, McArthur, and Haughey. Under their guidance and with their support, I will
receive technical training in experimental concepts and development of appropriate methodologies, which will
be complimented by networking opportunities at national and international scientific meetings. Successful
completion of the mentorship, didactic training, research, and career development activities afforded by this
K99/R00 Pathway to Independence Award will provide the strong foundation necessary for my successful
transition to an indep...

## Key facts

- **NIH application ID:** 10020179
- **Project number:** 5R00DA044838-04
- **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:** $244,152
- **Award type:** 5
- **Project period:** 2019-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020179

## Citation

> US National Institutes of Health, RePORTER application 10020179, COCAINE USE AND HIV ANTIRETROVIRAL THERAPY EFFICACY IN THE CNS (5R00DA044838-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10020179. Licensed CC0.

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