# Identification of immune protective pathways dysregulated by opioid use in HIV infection, using a systems biology-based approach, toward the goal of pharmacological restoration of immune function

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $14,168

## Abstract

Abstract
In the era of combination antiretroviral therapy (cART) for HIV infection, a major focus of clinical and scientific
investigation lies with the high risk of cardiovascular disease, neurocognitive disorders, nephropathy, and
malignancy among persons with HIV (PWH). While strategies are being developed to identify and reverse the
latent pool of viral reservoirs, a parallel effort must proceed to enhance immune defenses against viral
persistence as well as re-establish immune homeostasis. The focus of this mechanistic proposal is to identify
pathways, molecular targets, and small molecule compounds that regulate immune protection in the HIV patient,
whose immune function is compromised by chronic opioid use. We hypothesize that defining the unique
biochemical signal transduction pathways emanating from all three subtypes of opioid receptors in
human T lymphocytes will reveal specific molecular targets that affect the responsiveness of the immune
system in HIV+ and HIV- persons with Opioid Use Disorder. This work capitalizes on our recent findings that
the G-protein coupled cAMP and the arrestin-associated Mitogen Activated Protein kinase (MAPK) signal
transduction pathways triggered by endogenous, semi-synthetic, and synthetic opioids are distinctly and uniquely
regulated in human T lymphocytes. This summer intern’s project will focus on the following Specific Aim:
Aim 1 for the NIDA Summer Undergraduate Research Intern:
Identify molecular signal transduction pathways in CD8+ and CD4+ T cells that are differentially triggered
by opioid agonists, selective for each of the three opioid receptors.
Our overall goal is to generate a refined list of therapeutic targets for pharmacologic restoration of immune
function in persons with HIV that require opioid therapy for analgesia.

## Key facts

- **NIH application ID:** 10398591
- **Project number:** 3R01DA043253-05S3
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Alan David Levine
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $14,168
- **Award type:** 3
- **Project period:** 2016-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10398591

## Citation

> US National Institutes of Health, RePORTER application 10398591, Identification of immune protective pathways dysregulated by opioid use in HIV infection, using a systems biology-based approach, toward the goal of pharmacological restoration of immune function (3R01DA043253-05S3). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10398591. Licensed CC0.

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