# Characterization of cocaine induced signaling pathways that enhances HIV transcription

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2021 · $9,828

## Abstract

TITLE: Assessing the impact of cocaine and HIV in accelerating aging process
Accelerated aging is a complication of HIV infection despite the effectiveness of highly active antiretroviral therapy
(HAART or ART). This is due, in part, to HIV-associated neurological disorders (HAND) which are caused mainly
by the ongoing immune activation and inflammation in the CNS. There is considerable evidence that suggests an
additive or synergistic effect of cocaine on the persistence and severity of neurocognitive dysfunction in HIV-
infected patients. Therefore, the relationship between drugs of abuse, such as cocaine, HIV infection,
neurodegeneration and accelerated aging is of particular interest.
Overall goal of the proposed investigation is to understand the underlying mechanisms through which cocaine
use further accelerates the aging process in HIV infected individuals by enhancing immune activation and
inflammation. Currant anti-HIV therapy is unable to restrict HIV protein production. Certain HIV proteins are
toxic, especially to the CNS, as they stimulate pro-inflammatory cytokines and immune activation. Cocaine
further enhance HIV protein production. The investigation proposed in this application will establish that
cocaine accelerates the aging process by comparing cocaine treated and untreated HIV-infected both
lymphoid and myeloid cells. Results will be confirmed in PBMCs of HIV-infected subjects with or without
cocaine exposure.
The following aims are proposed to confirm and quantify the impact of cocaine in promoting premature aging:
Aim 1A: Analysis of cell surface markers of immune activation and inflammation, selectively triggered by
cocaine
Aim 1B: Investigate the potential impact of cocaine exposure on cell senescence
Aim 1C: Determine the cocaine effect on cell exhaustion
Aim 2: Define the plasma markers of immune activation and inflammation following cocaine use
Aim 3: Examine the impact of cocaine on telomere length, telomerase transcript, protein and activity.
The investigation proposed in this application will establish that cocaine accelerates the aging process by
comparing cocaine-using HIV infected subjects with those not using cocaine.

## Key facts

- **NIH application ID:** 10399877
- **Project number:** 3R01DA041746-03S1
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Mudit Tyagi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $9,828
- **Award type:** 3
- **Project period:** 2017-09-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399877

## Citation

> US National Institutes of Health, RePORTER application 10399877, Characterization of cocaine induced signaling pathways that enhances HIV transcription (3R01DA041746-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10399877. Licensed CC0.

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