# Synthetic fentanyls adversely affect the blood-brain barrier and HIV replication in the context of neuroHIV

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2024 · $726,849

## Abstract

In the past two to three decades, there has been a surge in the use, abuse, and misuse of opioids. Among
opioid users, Illicit fentanyl use has become widespread in the US. Moreover, synthetic fentanyls rapidly flood
the illicit drug market due to their cheap manufacturing, enhanced potency, and chemical composition that
evades toxicology screening. Furthermore, black-market drug makers create new fentanyl analogs to avoid
classification as illegal, to get around policy restrictions. Although drugs of abuse and HIV are entwined
epidemics, it is becoming clear that Fentanyl plays an alarming role in new outbreaks. Recent reports suggest
that there's an elevated risk of acquiring HIV-1 infection in those who inject fentanyl. Additionally, fentanyl is
commonly detected in urine drug-screen tests in people living with HIV (PLWH). Advances in antiretroviral
therapy has extended the lives of PLWH. However, as people live longer, the risk of altered neurological
manifestations increases. It is also well known that drugs of abuse compound these effects of HIV. Even
though it is known that opioids and their receptors are implicated in the pathogenesis of NeuroHIVs, there's
essentially no information available about whether fentanyl has effects on the status of HIV infection in the
CNS. In this study, we will examine the overall hypothesis that: fentanyl and novel synthetic fentanyl
analogs facilitates HIV-1 leukocyte transendothelial migration, microglial HIV infection/replication and
impairs the integrity and function of the BBB. We propose three specific aims to explore the hypothesis.
In Aim 1, using our latest tissue-engineered microfluidic model of the human BBB, we will perform analyses of
the kinetic changes in BBB permeability, transporter status and immune-endothelial interaction in response to
fentanyl and other synthetic fentanyls. Since microglial is the primary refuge for HIV in the brain, Aim 2 will
determine the effects of synthetic fentanyls on dynamic HIV-1 infection in the resident immune cell of the brain,
the microglial. Comparisons will be made to monocyte derived macrophages. Aim 3 will examine the molecular
mechanism responsible for a dysfunctional BBB by fentanyls. This proposal comprehensively addresses the
key tenets of RFA-DA-23-012 and features multiple synthetic fentanyls, a translational model of the BBB, and
experiments to define the underlying molecular mechanism involved. Our studies will provide important insights
on how the interplay of two major pathologic factors (HIV and fentanyl) in the CNS impair the BBB and
compromise the intracellular anti-HIV immunity of microglia, the key mechanisms that could significantly
accelerate the development NeuroHIV.

## Key facts

- **NIH application ID:** 11098183
- **Project number:** 7R01DA058536-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Allison Michelle Andrews
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $726,849
- **Award type:** 7
- **Project period:** 2023-08-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11098183

## Citation

> US National Institutes of Health, RePORTER application 11098183, Synthetic fentanyls adversely affect the blood-brain barrier and HIV replication in the context of neuroHIV (7R01DA058536-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11098183. Licensed CC0.

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