# Dopamine system as reporter of HIV status and inflammation in Meth abusers

> **NIH NIH R01** · SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE · 2020 · $432,000

## Abstract

Dopamine system as reporter of HIV status and inflammation in Meth abusers
HIV life-expectancy has increased with anti-retrovirals, but the consequences of the virus in end-organs such
as the Central Nervous System (CNS) have not been mitigated. Moreover, co-morbidities such as substance
use can aggravate CNS disorders in HIV infection, impacting viral replication and inflammation.
Methamphetamine (Meth) is a popular addictive drug associated with risk of HIV infection, and a powerful
inducer of dopamine (DA), a neurotransmitter that regulates reward circuits in the brain. Inflammatory
biomarkers such as plasma CD163 and IL6 levels correlate with HIV-induced cognitive deficits, including in
Meth abusers. They indicate that an inflammatory process is taking place in the brain, but may not be able to
predict risk of development of CNS inflammation in Meth abusers, or monitor improvements in cognitive
performance in the context of HIV. Innate immune cells are the main HIV target cells in the CNS. Importantly,
these cells express DA receptors (DRDs), and therefore are responsive to the hyperdopaminergic environment
generated by Meth abuse. We hypothesize that the expression of molecules of the DA system, as well as
inflammatory markers resulting from DA signaling, are sensitive biomarkers that may be incorporated into a
panel of tools with the capacity to predict susceptibility and to assess therapeutic efficacy in the blood of HIV+
subjects that are Meth-abusers. We also hypothesize that the individual genetic background can bias the
balance between D1-like and D2-like DRD subtypes, and their resulting inflammatory signatures affecting HIV
latency or replication phenotypes. We propose studies in human peripheral cells that bridge basic
science findings with translational applications of high impact, for screening DRD subtypes
expression levels and sequence, as well as inflammatory signatures associated with these subtypes as
predictors of risk to the development of cognitive deficits in Meth abusers, in the context of HIV. Our
integrated approach is targeted to predict and monitor neuro-immune-viral disruptions, and generate tools to
become incorporated in clinical therapeutic decisions. It will provide invaluable data to fill the existing gap in the
knowledge and in the needs of markers with real-time clinical value, with the potential for critically monitoring
the efficacy of therapy in the CNS, or for predicting susceptibility to disabling neurological syndromes in HIV+
individuals that are drug abusers.

## Key facts

- **NIH application ID:** 9852999
- **Project number:** 5R01DA047822-02
- **Recipient organization:** SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** Maria Cecilia Garibaldi Marcondes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,000
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852999

## Citation

> US National Institutes of Health, RePORTER application 9852999, Dopamine system as reporter of HIV status and inflammation in Meth abusers (5R01DA047822-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9852999. Licensed CC0.

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