# Immune System Modeling/HIV

> **NIH NIH R01** · TRIAD NATIONAL SECURITY, LLC · 2021 · $385,317

## 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 of their virus below the limit of detection for a
median of 89 months after stopping therapy. Persaud et al. described a HIV-1 infected infant who
started ART within 30 hours after birth, discontinued therapy at 18 months of age, then remained
undetectable, off-therapy, for 27 months before the virus rebounded. A recent study showed that
SIV-infected macaques on ART given an antibody (Ab) against the integrin α4β7 could maintain
undetectable plasma viremia for over 9 months after all treatment was stopped. Finally, treatment
with broadly neutralizing Abs (bnAbs) in some macaques infected with SIV also led to virological
control for an extended period even after completion of Ab treatment.
To realize the promise of these advances, we need a better understanding of the factors that lead
to establishment of undetectable or controlled viral loads in the absence of treatment. Here we
propose to develop a set of new models to help understand how functional cure was
obtained in the studies mentioned above and to understand more generally under what
conditions and interventions functional cure can be achieved. To this end, we will collaborate
with leading experimental scientists, who will provide novel datasets that will allow us to fulfil the
following specific aims. Aim 1. Determine the mechanisms of action of HIV-1 specific bnAbs
in vivo. We will develop new models of antibody action, incorporating multiple biological
functions, to explain experiments of bnAbs infusions in HIV-infected humans and SIV-infected
macaques. These models will help determine the main mechanisms of action of bnAbs. Aim 2.
Determine whether treatment with monoclonal antibodies can lead to a change in viral load
set-point. We will develop models with multiple stable steady states of viral load (high and low
levels) driven by the interplay between immune responses and the establishment of the latent
reservoir. These models will be calibrated by experimental data in humans and in the macaque
model of SIV and will provide a mechanistic picture of the effects of these antibodies. Aim 3.
Determine the within host dynamics of Zika virus infection and predict the effects of
therapy. We will leverage the work in the previous aims to develop models for this emerging
infection and study the effects of different therapies, including antibodies, in controlling Zika virus.

## Key facts

- **NIH application ID:** 10212927
- **Project number:** 5R01AI028433-31
- **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:** $385,317
- **Award type:** 5
- **Project period:** 1990-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212927

## Citation

> US National Institutes of Health, RePORTER application 10212927, Immune System Modeling/HIV (5R01AI028433-31). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10212927. Licensed CC0.

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