# Simulating persistence and elimination of the HIV reservoir

> **NIH NIH K25** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $123,030

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal describes a five-year research training program that will allow Dr Reeves to transition from a
quantitative researcher in physics and achieve his long-term goal of becoming an independent biomedical
researcher. Dr Reeves will develop a phylodynamic mathematical model, validated on diverse experimental
data, to improve the understanding of the creation, persistence, and elimination of the HIV reservoir.
 The training program incorporates the expertise of an outstanding group of mentors and collaborators.
Dr Reeves’s scientific advisory committee includes experts in modeling infectious diseases (Dr Josh Schiffer),
HIV cure (Dr Keith Jerome), viral evolution (Drs Morgane Rolland and Trevor Bedford), HIV reservoirs (Drs
Robert Siliciano and Peter Hunt), and statistics (Dr Peter Gilbert). This group is dedicated to ensuring the
success of this project and the development of Dr Reeves’ career as an independent researcher. The proposal
also contains professional mentorship (Dr Karen Peterson). The specific learning goals required for a
successful transition to biological research will be accomplished through didactic coursework in virology,
immunology, and phylogenetics as well as conferences and professional training in the skills of a successful
mentor and group leader.
 Currently, no cure for HIV exists. Individuals living with HIV face the difficult prescription of a lifetime of
daily antiretroviral therapy (ART). Understanding the persistence of HIV during ART is the paramount scientific
question standing between standard of care treatment and cure. Aim 1 is directed at developing a
phylodynamic model of primary infection and the creation of the HIV reservoir. The model will be validated
against viral load and sequence data from the RV217 trial, the highest-resolution primary infection cohort
recorded (shared by Dr Rolland). Dr Reeves has recently published a model in Nature Communications that
suggests the majority of reservoir persistence is due to cellular proliferation of infected cells. Aim 2 is a logical
continuation of this work. Dr Reeves will model T cell subset and phylogenetic data (shared by Drs Hunt and
Siliciano) to refine the mechanism as predominantly homeostatic vs antigenic proliferation. For Aim 3 Dr
Reeves will use the phylodynamic model as a biomarker discovery tool for curative interventions including
latency reversing agents, anti-proliferative therapy, and gene therapy.
 Through accomplishing the aims of this proposal, Dr Reeves will address critical gaps in our knowledge
of the HIV reservoir’s persistence and provide a framework to study HIV cure regimens in silico. Ultimately, this
proposal will allow Dr Reeves to influence the future of HIV cure research as well as build a self-sustaining
program at the interface of mathematical modeling, immunology, and viral evolution.

## Key facts

- **NIH application ID:** 10083066
- **Project number:** 1K25AI155224-01
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Daniel Reeves
- **Activity code:** K25 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $123,030
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083066

## Citation

> US National Institutes of Health, RePORTER application 10083066, Simulating persistence and elimination of the HIV reservoir (1K25AI155224-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10083066. Licensed CC0.

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