# Project 002 - VIDI

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $675,613

## Abstract

PROJECT 2. Viral Immunology, Drugs, and Imaging (VIDI) Research Project - ABSTRACT
Despite the success of antiretroviral therapy (ART) improving the lives of persons with HIV (PWH), curing HIV
would be important to reduce stigma and long-term co-morbidities associated with HIV infection that occur even
during ART. Developing a successful cure will need to better identify the viral and host factors that govern HIV
dynamics in its HIV Obligate MicroEnvironment (HOME) to identify reservoir vulnerabilities that can be targeted.
The Viral Immunology, Drugs, and Imaging (VIDI) Research Project (RP) will focus on immune, pharmacological,
host epigenetic cellular environments, and tissue architecture that govern the continuum of HIV reservoir
dynamics. This characterization by the VIDI RP alone will add considerable new knowledge to the field. In the
HOME program, these assay results will be integrated with viral features of HIV reservoir dynamics characterized
by VENI RP, and all datasets will be further integrated and analyzed by VICI RP.
For experimental planning, the HIV reservoir dynamic continuum is simplified as the following reservoir states:
· Leaves HOME when HIV (re)activates from tissues during antiretroviral therapy (ART) (i.e., like packing its
 bag and getting ready to leave) and causes rebound viremia during ART interruption.
· Comes HOME when HIV (re)populates tissues during viremia off ART and through the spread of clonally
 expanded HIV-infected cells while on ART. (Clonal expansion is like adding family to the home.)
· Stays HOME when HIV (silently) persists in blood and tissue reservoirs (on and off ART).
To optimize allocated resources, we developed a two-step Adaptive Learning Approach. During the Mapping
phase, the VIDI RP will examine how cellular and soluble inflammatory milieus and ART levels are associated
with each reservoir state (i.e., leaving, coming, staying). The VICI RP will assist in the integration and analysis
of these data to identify ‘samples-of-interest’ that have pre-defined reservoir states and sufficient cellular
environment for deeper investigation. In the Confirmation phase, the VIDI RP will use single-cell and imaging
technologies to further characterize environmental factors associated with reservoir dynamics at a deeper level.
Importantly, the feasibility of our VIDI RP is greatly enhanced by the knowledge gained from our previous P01
(AI131385) and its Last Gift Cohort, which collects pre- and post- mortem specimens from PWH who did (n=5)
or did not stop ART (n=15) before death. The HOME program will allow the continuation of this cohort while
expanding the science to study HIV dynamics across the human body at the single-genome and single-cell level.
In summary, the overall HOME program will provide a deep delineation of environmental factors governing HIV
reservoir dynamics, which is directly responsive to the Understanding HIV Reservoir Dynamics RFA AI-21-013.
This new knowledge will inform HIV cure st...

## Key facts

- **NIH application ID:** 10602744
- **Project number:** 5P01AI169609-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Sara Gianella Weibel
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $675,613
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10602744

## Citation

> US National Institutes of Health, RePORTER application 10602744, Project 002 - VIDI (5P01AI169609-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10602744. Licensed CC0.

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