# Tyrosine kinase inhibition to block HIV-1 persistence: a pilot study

> **NIH NIH R34** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $228,750

## Abstract

PROJECT SUMMARY
Despite the success of antiretroviral therapy (ART), people living with HIV-1 require life-long treatment due to
viral persistence in long-lived cellular reservoirs, and experience a chronic state of immune activation and
exhaustion that significantly contributes to the risk of cardiovascular disease and other life-threatening
complications. The inability to address these clinically relevant shortcomings of ART represents a critical
knowledge gap in the management of HIV-1 infection. Intensive efforts to perturb the latent reservoir via
pharmacologic latency reversal or immune-based therapies targeting latently infected cells have not produced
positive results to date. Similarly, attempts to directly address the chronic immune activation observed in
chronic, treated HIV-1 infection have shown modest returns. The reservoir persists through cellular
proliferation, though little effort has been made to evaluate the role of anti-proliferatives in reducing reservoir
size. We and others have demonstrated the anti-proliferative and anti-HIV-1 effects of the FDA-approved drug
and tyrosine kinase inhibitor dasatinib. While dasatinib has never been trialed for this indication, it was recently
shown in a pilot clinical trial to act as a ‘senolytic,’ or a drug that can target cells responsible for the chronic
inflammation associated with aging and aging-related conditions. The overall aim of this proposal is to plan a
pilot clinical trial administering dasatinib to individuals living with treated HIV-1 infection to evaluate its ability to
reduce the size of the HIV-1 reservoir and ameliorate the chronic immune activation that contributes to CVD
risk in this population. The importance of developing strategies to address HIV-1 persistence,
immunosenescence and serious pathophysiologic consequences including cardiovascular disease in treated
HIV-1 infection are underscored by the chronologic aging of the HIV-1 infected population in the United States.
The proposed pilot trial testing the anti-proliferative and senolytic properties of dasatinib in treated HIV-1
infection will have therapeutic implications for HIV-1 infection and a multitude of aging-related disease states
including CVD.

## Key facts

- **NIH application ID:** 10085120
- **Project number:** 1R34AI155317-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Adam Mitchell Spivak
- **Activity code:** R34 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,750
- **Award type:** 1
- **Project period:** 2020-08-19 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085120

## Citation

> US National Institutes of Health, RePORTER application 10085120, Tyrosine kinase inhibition to block HIV-1 persistence: a pilot study (1R34AI155317-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10085120. Licensed CC0.

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