# The brain as a SIV reservoir under suppressive cART potentiation by drugs of abuse

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $752,188

## Abstract

Abstract
 Despite effective treatments for HIV, the presence of viral reservoirs has prevented the development of
a cure for HIV infection. Although most reservoir work has focused on CD4+ T cells, these are not the primary
infected cells in the CNS instead long-lived macrophages and microglia are infected. Furthermore, many of the
anti-retroviral treatments do not penetrate the brain. In addition, drug abuse is frequently co-morbid with HIV
infection and affects CNS virus and disease. Studying the state of virus in the brain, as well as doing controlled
experiments with drugs of abuse, cannot be performed in humans. Here we will use the highly relevant SIV-
infected macaque model treated with an effective anti-retroviral treatment regimen in three groups: those
receiving the stimulant methamphetamine, those receiving the opiate morphine and those receiving no drugs
of abuse. Our experimental design will test the hypothesis that the brain is a reservoir under controlled
treatment regimens and determine the effects drugs of abuse have on such a reservoir. In parallel, we will
examine a known reservoir (lymph node CD4+ T cells), both as a comparison and to illuminate additional
effects of drugs of abuse on reservoirs.
 Specific Aim 1 will examine the effects of drugs of abuse on modulating the effectiveness of
antiretroviral treatment in SIV infected macaques. Innovative aspects include our hypothesis based
mechanistic studies examining changes in cellular markers that may impact infection and tissue migration, and
our analyses of intracellular antiretroviral concentrations uniquely performed here in brain cells as well as in
lymphoid cells in the setting of drugs of abuse. Specific Aim 2 will utilize a series of state of the art assays to
examine the hypotheses that under suppressive anti-retroviral treatment, the brain is indeed a viral reservoir
for SIV and substance abuse increases the size of this reservoir. We will utilize PCR detection, viral outgrowth
in indicator cells and the highly sensitive TILDA assays to examine virus in microglia/macrophages purified
from the brains of the animals in Aim 1. To ensure a definite result with high sensitivity and specificity, we will
adoptively transfer infection to naïve monkeys as a new platinum standard for reservoir detection to definitely
address this question of the CNS as a reservoir and the effects of drugs of abuse. Such knowledge is crucial
for devising strategies to cure HIV infection, including in drug abusers.

## Key facts

- **NIH application ID:** 10000087
- **Project number:** 5R01DA043164-05
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Shilpa J Buch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $752,188
- **Award type:** 5
- **Project period:** 2016-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000087

## Citation

> US National Institutes of Health, RePORTER application 10000087, The brain as a SIV reservoir under suppressive cART potentiation by drugs of abuse (5R01DA043164-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10000087. Licensed CC0.

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