# Modeling Viral and T Lymphocyte Dynamics

> **NIH NIH R01** · TRIAD NATIONAL SECURITY, LLC · 2021 · $466,632

## Abstract

SUMMARY
Multiple recent studies have provided proof-of-concept that a “functional cure” of HIV-1 infection,
i.e. long-term control of HIV without continued treatment, is achievable. The VISCONTI study
identified 14 HIV+ patients, who received antiretroviral treatment (ART) during primary HIV-1
infection, and maintained post-treatment control (PTC) of their virus below the limit of detection
for a median of 89 months after stopping therapy. The CHAMP (Control of HIV after Antiretroviral
Medication Pause) study has identified 67 post-treatment controllers from 14 treatment
interruption studies involving more than 700 participants.
To determine why some individuals control HIV to undetectable or low levels after treatment
discontinuation, we need a better understanding of the factors that lead to establishment of viral
reservoirs, that determine its size, the dynamics of its maintenance and its reactivation possibly
leading to viral rebound after treatment cessation. Here we propose to develop a set of new
models to help understand the factors that led to functional cure in the studies mentioned
above and to understand more generally how functional cure can be achieved. We will
collaborate with leading experimental scientists, who will provide novel datasets allowing us to
fulfil the following specific aims. Aim 1. To understand the mechanism of HIV latent reservoir
establishment and the factors determining the rate of reservoir seeding during acute
infection. We will develop mechanistic models of early reservoir establishment. We will test these
models against rich datasets collected by collaborators and estimate key parameter values to
accurately describe the dynamics of reservoir establishment. With the insights gained, we will
extend the model to interpret recent data39 on the seeding, turnover and the genetic composition
of the reservoir. Aim 2. To understand in quantitative detail the factors that determine the
duration of post-treatment control after ART interruption. We will study new models that
account for patient specific factors such as the ART regime and the level of cell-associated RNA
at the time of ATI in predicting time to viral rebound after ATI. When the time to rebound is long,
we aim to elucidate new factors such as a time-dependent rate of reservoir reactivation or immune
control that lead to prolonged PTC. Aim 3. Using insights gained from mathematical modeling
to propel the cure agenda for HBV. We will leverage previous modeling successes of HIV and
HCV infection to develop a new generation of models of HBV infection and study the effects of
different therapies singly and in combination.

## Key facts

- **NIH application ID:** 10076869
- **Project number:** 5R01OD011095-28
- **Recipient organization:** TRIAD NATIONAL SECURITY, LLC
- **Principal Investigator:** ALAN S PERELSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,632
- **Award type:** 5
- **Project period:** 2019-12-23 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076869

## Citation

> US National Institutes of Health, RePORTER application 10076869, Modeling Viral and T Lymphocyte Dynamics (5R01OD011095-28). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10076869. Licensed CC0.

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