# OMICs to define impact of cocaine on immunity and HIV persistence in  treated HIV infection

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $531,979

## 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, and incomplete
measurement of immune function in these subjects. We have used systems biology to identify mechanisms of
immune mediated protection. We have provided strong evidence that the balance between pro and anti-
inflammatory pathways in cells is disrupted even in cART treated subjects. Disruption of this balance leads to
poor immune reconstitution in HIV infected cART treated subjects and to increased frequencies of latently
infected cells. We have access through our collaborators at FIU to a well-characterized cohort of cART treated
subjects who are also cocaine users and who are well monitored for their cocaine use. Cocaine use as shown
by our preliminary results account for further perturbation of the balance between pro and anti inflammatory
effector molecules and cells; this results in lower levels of immune reconstitution in these subjects and
potentially to higher HIV persistence. We will use state of the art approaches to address our major objective:
we will delineate the molecular mechanisms that result in the immune dysfunction and HIV persistence
observed in cocaine users cART treated subjects. In specific aim 1 we will use polychromatic flow cytometry to
characterize the distribution and function of pro and anti-inflammatory cells including Treg subsets and
determine their association to loss of T cell homeostasis and poor immune reconstitution post cART
Transcriptional profiling of different memory T cell subsets will lead to the identification of molecular pathways
in cocaine users which are associated to disrupted CD4 T cell homeostasis; these mechanistic findings will be
validated at the single cell level by flow cytometry and by Fluidigm Biomark TM . Our preliminary results
indicate that in cocaine users CD8 T cells express markers associated to deregulated homeostasis. We will
determine the impact of cocaine on HIV specific CD8 T cell responses and assess if these are associated to
the imbalances in the inflammatory environment or they are due to the lack of CD4 T cell help. In specific aim 2
we will assess and define mechanisms associated to the impact of cocaine on HIV persistence. We have
developed two new assays that will provide critical insights to the magnitude of the HIV reservoir and to the
impact of cocaine on HIV persistence. TILDA will allow us to monitor the frequencies of inducible HIV viruses
and to provide a quantitative assessment of the impact of cocaine on establishment and maintenance of the
HIV reservoir ex vivo in infected subjects. LARA will allow us to determine in vitro that cocaine and its
metabolite...

## Key facts

- **NIH application ID:** 10321501
- **Project number:** 7R01DA042712-06
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rafick Pierre Sekaly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $531,979
- **Award type:** 7
- **Project period:** 2020-12-23 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10321501

## Citation

> US National Institutes of Health, RePORTER application 10321501, OMICs to define impact of cocaine on immunity and HIV persistence in  treated HIV infection (7R01DA042712-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10321501. Licensed CC0.

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