# A Systems Biology Approach to HIV-associated Neurocognitive Impairment: Role of Drug Abuse and Neuroinflammation

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $608,153

## Abstract

Project Summary
 Even in the era of widespread combination antiretroviral therapy, over half of HIV-infected patients
experience HIV-associated neurocognitive impairment (NCI). NCI is driven in part by persistent neuro-
inflammation with activated monocytes and T cells playing pathogenic roles. Marijuana and cocaine, two of the
mostly commonly abused drugs among HIV-infected persons, cause alterations in neural and cognitive
functioning, and have significant immunomodulatory effects. While the effects of HIV infection and drug abuse
on immune dysfunction and inflammation, brain structure/function, and NCI have been independently studied,
the complex interactions between these biological systems are poorly characterized. Our preliminary work
suggests that cocaine and marijuana use have discordant effects on NCI in persons with HIV, with differential
impacts across domains of cognitive function. In addition, research has shown that stimulants like cocaine
induce an activated immune state, whereas marijuana has anti-inflammatory effects. Building on the prior work
of our multi-disciplinary team, with complementary expertise in neuroscience, drug addiction, HIV immunology,
and computational biology, the proposed research uses a systems biology approach to investigate the effects
of cocaine and marijuana on immune function, brain structure/function, and neurocognition in HIV-infected
persons. We aim to: (1) identify the independent and joint effects of cocaine and marijuana use on MRI
measures of cerebral volume, white matter integrity, and functional connectivity, and on behavioral measures
of neurocognition; (2) quantify differences in peripheral and CNS immune function between marijuana and
cocaine users; and (3) employ a systems biology approach to integrate immunology, neuroimaging, and
behavioral data into a multi-level predictive model. Our guiding hypothesis is that cocaine induces an immune
activated state that causes alterations in brain structure/function and cognitive impairment, while marijuana
attenuates these effects through anti-inflammatory processes. The sample will include 150 adults with HIV
infection who use cocaine only, marijuana only, cocaine and marijuana, or neither drug, comprising 4 distinct
groups (~37/group). At study completion, we will have produced a comprehensive, multi-disciplinary dataset,
and our systems biology approach will provide significant insights to generate novel hypotheses for future
research on the complex biological intersection of HIV and substance use. This proposal addresses both a
critical need to identify “factors that impact differences in neurocognitive impairment in association with specific
patterns of substance abuse” [RFA-DA-16-013] and multiple high priority topics for AIDS-designated funding,
including investigation of HIV-associated comorbidities such as neurological complications and understanding
the basic biology of immune dysfunction and HIV transmission [NOT-15-137]. This innovative p...

## Key facts

- **NIH application ID:** 9977138
- **Project number:** 5R01DA043241-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** CHRISTINA S MEADE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $608,153
- **Award type:** 5
- **Project period:** 2016-09-15 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977138

## Citation

> US National Institutes of Health, RePORTER application 9977138, A Systems Biology Approach to HIV-associated Neurocognitive Impairment: Role of Drug Abuse and Neuroinflammation (5R01DA043241-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9977138. Licensed CC0.

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