# PROBING the DYNAMICS of INFANT IMMUNITY to LIMIT HIV PERSISTENCE

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $797,395

## Abstract

The existing knowledge of perinatal HIV-1 infection on developing immunity is limited, and a need exists to
define the unique characteristics of immunity in infants that influence pediatric disease progression. The long-
term goal of this project is to develop a pathway to achieve durable remission for infants in the absence of
prolonged drug treatment. The central hypothesis is that understanding the quality and magnitude of the innate
and adaptive immune systems of newborns in response to HIV-1 infection is essential for developing better
strategies to achieve durable remission of HIV-1. The project will first address pathogenesis of perinatal HIV
infection, with and without ART, using a proven pre-clinical model of SHIV infection in newborn macaques. For
human infants, the incidence of infection is greatest between late stages of gestation and early weeks of
postpartum. Infection in utero or peripartum without early ART intervention leads to high mortality in the first
year of life. The risk of death is about half as great if infection occurs postnatally during breastfeeding. To
mirror peripartum infection, newborn macaques will be infected within the first few weeks of life (< 2 weeks old)
with SHIV by the oral route. Using serial sacrifices, the macaque experiments will allow for a comprehensive
evaluation of B cell and T cell function in blood, and multiple lymphoid and gut tissues at specific timepoints
during infection. The effect of an immature immune system at the time of infection on immune dysfunction and
disease progression will be assessed and compared between groups of animals that receive daily ART starting
within days of infection versus no ART groups. In addition to studying the impact of viremia on immune cell
function and viral reservoir kinetics, experiments in Years 2–4 will examine viremia rebound in infants after
modulating and potentially protecting adaptive immunity by limiting viral replication during the first week of
infection with ART. To mitigate immune dysregulation, further modulation of immune responses will be
assessed with the addition of potent neutralizing antibodies to complement the intervention strategy during and
just prior to ART cessation. Together, these studies will inform current clinical practices that are poised to
advance very early ART in circumstances of in utero or intrapatrum infection, but are challenged by incomplete
pre-clincal data to guide future practices at or near delivery. The proposed approaches and methodologies that
can be used in a nonhuman primate model but are not feasible in human infants will provide mechanistic
evidence of when and how active viral reservoirs can be prevented, reduced, or eliminated. Innovative
technologies, including the use of a new Primate Multimodal Imaging Core at the Oregon National Primate
Research Center, will provide access to state-of-the-art reagents and expertise for imaging viral latency,
reactivation, and treatment in macaques in real time using...

## Key facts

- **NIH application ID:** 9977916
- **Project number:** 5R01AI133712-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Nancy L Haigwood
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $797,395
- **Award type:** 5
- **Project period:** 2017-08-03 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977916

## Citation

> US National Institutes of Health, RePORTER application 9977916, PROBING the DYNAMICS of INFANT IMMUNITY to LIMIT HIV PERSISTENCE (5R01AI133712-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9977916. Licensed CC0.

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