# Effect of buprenorphine on monocytes in the context of neuroAids and opioid abuse

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $719,921

## Abstract

Abstract
A significant number of HIV+ people are opiate users, and injection drug use and associated risky behaviors
contribute to new cases of HIV infection. Antiretroviral therapy (cART) has changed the predominant
phenotype of HIV neuropathogenesis from HIV dementia to milder forms of HIV associated neurocognitive
disorders (HAND). Opiate abuse increases the severity of HIV brain disease in immunodeficient people and
similar effects are expected, but have not been fully defined, for mild HIV brain disease under cART. Because
mild HAND is a chronic, life-long dysfunction, therapies are needed both to mitigate mild HAND as well as to
limit the potential exacerbating effects of opiates on the disease. We propose to conduct research in vitro and
in a mouse model of HIV induced HAND to test our novel hypothesis that buprenorphine, an established opiate
medication, may serve such a dual therapeutic purpose. Methadone and buprenorphine are used to treat
opiate addiction, but buprenorphine is often preferred due to its safety profile. Buprenorphine also differs from
methadone, a full µ opioid receptor (MOR) agonist, in that it is a partial agonist of MOR and a full antagonist of
κ opioid receptors (KOR). Some opioid users treated with buprenorphine show improvement in cognition
compared to those on methadone, but the mechanism of improvement is unknown. Studies established that
circulating CD14+CD16+ monocytes are infected with HIV and suggested that chemokine mediated
transmigration of these infected and uninfected cells across the blood brain barrier (BBB) contributes to HAND
through seeding the brain with HIV and mediating chronic neuroinflammation. A recent clinical study showed
that the HIV DNA burden in CD14+ monocytes in people on cART predicts severity of their cognitive
impairment. Circulating leukocytes, including monocytes, express opioid receptors, and our preliminary data
show that human CD14+CD16+ monocytes express MOR and KOR. Using the chemokine CCL2 as a model of
inflammation, we also demonstrated that buprenorphine inhibits CCL2-induced adhesion of these cells to brain
microvascular endothelium as well as their CCL2-induced chemotaxis. Thus, buprenorphine inhibits important
components of CCL2 mediated CD14+CD16+ monocyte transmigration across the BBB. In preclinical studies
we showed that buprenophrine inhibits monocyte migration into the brain of EcoHIV infected mice. We also
demonstrated that EcoHIV induced cognitive impairment is improved by buprenorphine. A major goal of our
proposal is to correlate these 2 findings. Our overall hypothesis is that buprenorphine is a therapeutic that
will improve HAND by reducing/inhibiting CCL2 mediated CD14+CD16+ monocyte entry into the CNS,
contributing to improved cognitive functions due to decreased neuroinflammation not only in HIV
infected opioid abusers, but also in non drug abusing HIV infected people.

## Key facts

- **NIH application ID:** 9878088
- **Project number:** 5R01DA041931-05
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Joan Weinberger Berman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $719,921
- **Award type:** 5
- **Project period:** 2017-04-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878088

## Citation

> US National Institutes of Health, RePORTER application 9878088, Effect of buprenorphine on monocytes in the context of neuroAids and opioid abuse (5R01DA041931-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878088. Licensed CC0.

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