# An unbiased OMICs approach to identify mechanisms of Cocaine regulation of the HIV reservoir

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $743,904

## Abstract

PROJECT ABSTRACT
Substance abuse is associated with a more severe course of HIV disease as shown by the poor
immune reconstitution in cART treated subjects and an increased rate of co-morbidities. The
mechanisms that are involved in these poor clinical outcomes are not well understood most likely a
consequence of poorly- controlled confounding factors in study cohorts, lack of quantitative assessment of
drug levels,, incomplete measurement of immune function and poor understanding of the mechanisms that
lead to HIV persistence. We have used systems biology a n d shown that t h e balance between pro and anti-
inflammatory pathways a s major drivers of HIV persistence. Disruption of this balance leads to poor
immune reconstitution in HIV infected cART treated subjects and to increased frequencies of latently
infected cells. Cocaine use as shown by our preliminary results accounts for further perturbations of the
balance between pro and anti inflammatory effector molecules and cells which results in lower levels of
immune reconstitution in these subjects and perturbations in T cell homeostasis which have led to heightened
HIV persistence in other cohorts. We have assembled a multidisciplinary group that will allow us to overcome
these aforementioned hurdles and will use unbiased OMICs approaches to address our major objective which
is to delineate the molecular mechanisms triggered by cocaine that lead to HIV persistence. In specific aim 1
we will use three independent state of the art assays to quantity the size and cellular localization of the HIV
reservoir; we will use transcriptomics on specific cell subsets and other high density readouts including flow
cytometry and system serology to identify the effector cells and molecules that are associated to increased HIV
reservoir size. In specific aim 2 we will apply a global and targeted proteomics approach to validate
molecular pathways triggered by cocaine that lead increased HIV persistence. Metabolomics will be used to
identify the role of metabolites and particularly short chain fatty acids and cholesterol on HIV persistence. In
Specific Aim 3 we will validate the mechanisms identified by gene expression and proteomics which we have
shown in aims 1 and 2 to be associated to the impact of cocaine on HIV persistence; we will use a novel
primary cell assay of HIV latency which allows for the first time to measure latency reactivation in multiple T
cells subsets. LARA will allow us to confirm in vitro that cocaine and its metabolites can mobilize the above
identified pathways and monitor their impact on the establishment of HIV latency in different memory T cell
subsets and on the response to Latency Reactivating Agents.

## Key facts

- **NIH application ID:** 10321500
- **Project number:** 7R01DA043263-06
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rafick Pierre Sekaly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $743,904
- **Award type:** 7
- **Project period:** 2020-12-23 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10321500

## Citation

> US National Institutes of Health, RePORTER application 10321500, An unbiased OMICs approach to identify mechanisms of Cocaine regulation of the HIV reservoir (7R01DA043263-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10321500. Licensed CC0.

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