# Phylodynamic mechanisms of HIV reservoir seeding and maintenance

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $884,322

## Abstract

PROJECT SUMMARY
The HIV reservoir is a population of latently HIV infected cells that persists in people living with HIV on
suppressive antiretroviral therapy (ART) and prevents cure of HIV. Dr. Reeves and colleagues will study the
mechanisms that create and sustain the HIV reservoir throughout treated and untreated infection.
This team will use a mathematical modeling approach to integrate existing published and unpublished as well
as novel experimental data ranging across five stages of infection: early and chronic untreated (Aim 1) and early
and long-term treated, and analytical treatment interruption (Aim 2). Data will consist of HIV viral loads and
genetic sequences (RNA and DNA), cell counts (CD4+ and CD8+ T cells), and clonality of CD4+ T cells defined
by T cell receptor sequencing. We will adopt a novel within-host phylodynamic “wiphy” model to specifically study
HIV reservoir biology by specifically interrogating the various mechanisms driving its persistence vs. clearance
– including cellular proliferation of infected cells and adaptive immune selection against certain HIV sequences.
We will determine which mechanisms predominate in which stages, and provide a comprehensive understanding
of HIV reservoir creation, maintenance, and evolution throughout all infection stages.
This research will aid in the building of next-generation models of HIV reservoir seeding and persistence
dynamics. This work will help the HIV cure field gain a deeper understanding of how the HIV reservoir is created
during untreated infection and maintained during treated infection. Results should aid in efforts to design
therapeutics towards a functional or sterilizing HIV cure.

## Key facts

- **NIH application ID:** 11008739
- **Project number:** 1R01AI186721-01
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Daniel Reeves
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $884,322
- **Award type:** 1
- **Project period:** 2024-09-16 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11008739

## Citation

> US National Institutes of Health, RePORTER application 11008739, Phylodynamic mechanisms of HIV reservoir seeding and maintenance (1R01AI186721-01). Retrieved via AI Analytics 2026-08-11 from https://api.ai-analytics.org/grant/nih/11008739. Licensed CC0.

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