Locking HIV into a silent state to prevent reactivation
Official title: Targeted small molecule recruitment to suppress the HIV transcriptionally active reservoir
Funded at J. David Gladstone Institutes · NIH-11332984 · Data updated 2026-11-12
Researchers aim to develop drugs that keep HIV permanently silent to help people living with HIV, especially those who also have substance use disorders.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | J. David Gladstone Institutes NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project start | May 15, 2025 |
| Project end | March 31, 2030 |
| Funding year | 2026 |
| Award (this year) | $655,855 |
| NIH project number | 5R01DA063159-02 |
| Project ID | NIH-11332984 on NIH RePORTER |
Who could benefit from this research
✓Could help
Adults living with HIV—particularly those with co-occurring substance use disorders or concerns about viral reservoirs in the brain—would be the main future candidates for therapies developed here.
✕Less likely to help
People without HIV will not benefit, and individuals whose HIV is already stably suppressed with no risk of reactivation may not see direct benefit from these early-stage efforts.
What this research studies
The team is working to turn existing drugs that block a key cellular enzyme (CDK9) into safer agents that keep HIV turned off. They will test combining these CDK9 inhibitors with drugs that activate PP2A, a cellular switch, to strengthen the silencing effect. The project also builds a targeted chemical delivery approach that seeks to bring these drugs directly to the HIV genome using a bifunctional system tied to FKBP1 interactions. The goal is to make HIV-specific silencing stronger while reducing side effects that come from hitting other cellular processes.
Why it matters
Potential benefit: If successful, this could reduce chances of HIV reactivation and help prevent viral rebound, particularly in the brain, potentially lowering reliance on continuous treatment.
How similar studies have gone: Other 'block-and-lock' strategies have shown promise in lab and animal experiments but have not yet proven effective in people, so this work builds on preclinical leads.
Where this research is happening
-
J. David Gladstone Institutes
San Francisco, United States Active
Researchers
- Principal investigator: Ott, Melanie Maria — J. David Gladstone Institutes
- Study coordinator: Ott, Melanie Maria
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About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.