# Infant immune mechanisms of HIV reservoir size and decay

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $675,257

## Abstract

During early HIV infection, the virus stably integrates in long-lived cellular reservoirs which persist despite
continuous antiretroviral therapy (ART). ART initiation during early acute HIV infection may limit viral reservoir
size, reduce immune activation and improve treatment outcomes and post-treatment virologic control in adults
and children. There are scant data on reservoir dynamics and determinants from sub Saharan Africa, the
region of the world with most global pediatric HIV. We have previously demonstrated influence of antibody-
dependent cellular cytotoxicity (ADCC) on infant HIV acquisition and disease control. We have also
demonstrated marked plasticity of the natural killer (NK) cell population over the course of infancy and NK
suppression of HIV and acquisition in adult cohorts. It is plausible that these immune responses may influence
reservoir establishment and decay. Understanding these determinants could inform vaccine or therapeutic
strategies to accelerate reservoir eradication.
We have followed infants and older children for >5-10 years with serial PBMC and plasma collection and have
quantified HIV reservoir in a subset of children who started ART during the first year of life with viral
suppression from these cohorts. We propose mechanistic virology/immunogy studies leveraging these unique
repositories and to extend follow-up of these children to track longer term reservoir changes (>15 years since
ART initiation in some children). Our overarching aim is to determine reservoir dynamics and decay using
mathematical modeling and identify immune determinants of reservoir decline and size. This project will be led
by multiple PIs (MPIs): Drs. John-Stewart and Lehman. With our combined expertise in pediatric HIV
molecular epidemiology (John-Stewart, Wamalwa) virology (Lehman, Overbaugh), immunology (Slyker, Blish)
and modeling (Holte, Matsen) we propose to model longitudinal reservoir dynamics, and determine
effects of infant timing of HIV acquisition, ART timing, and the influence of infant immune activation,
ADCC, and NK population characteristics on reservoir decline and size. These studies will provide novel
data on reservoir dynamics during infancy and early childhood from sub Saharan Africa and will elucidate
potential influence of immune activation, ADCC, and natural killer phenotype in reservoir containment, and
ultimately inform intervention strategies for improved long-term management and reservoir control in HIV
infected children.

## Key facts

- **NIH application ID:** 9948741
- **Project number:** 5R01HD094718-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Grace C. John-Stewart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $675,257
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948741

## Citation

> US National Institutes of Health, RePORTER application 9948741, Infant immune mechanisms of HIV reservoir size and decay (5R01HD094718-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948741. Licensed CC0.

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