# The effect of cytomegalovirus, inflammation, and immune activation on neurodevelopment in children exposed to maternal HIV infection

> **NIH NIH P01** · UNIVERSITY OF WASHINGTON · 2022 · $892,566

## Abstract

Project 3 Summary / Abstract
Exposure to maternal HIV infection affects child development through complex intersecting social and biologic
pathways. Lower scores for cognition, attention, processing speed, and executive function have been reported
for HIV-exposed uninfected (HEU) children compared to HIV-unexposed (HUU) peers. Increasing evidence
indicates that exposure to maternal HIV-associated immune activation in utero, as well as systemic chronic
inflammation from infections acquired in early life, particularly cytomegalovirus (CMV), may contribute to
neurodevelopmental deficits in children. CMV elicits profound immune activation and inflammation following
infection, and has been associated with poorer growth, impaired motor functioning, and increased morbidity in
HEU children and children living with HIV (CLHIV). East African children acquire CMV early in life, with 40-60%
of HEU and HUU infected by 3 months of age. By contrast with HUU, HEU children acquire CMV earlier and
experience persistent systemic CMV viremia for many months, although the consequences of this for
development are currently unclear. Given the wealth of data linking early-life infections and inflammation to
neurodevelopmental delays, and the hyper-inflammatory effect of CMV at a critical age for brain development,
we propose to investigate the hypothesis that early acquisition of CMV and poorly-controlled CMV viremia in
HEU lead to chronic inflammation and immune activation, which leads to changes in growth and development.
We will leverage an existing longitudinal birth cohort study of HEU and HUU in Kenya in which enrollment and
follow-up started in the third trimester of pregnancy and continued for 2 years postpartum with intensive collection
of specimens and clinical data. Follow-up will be extended for 2 years to enable a detailed and sensitive
assessment of multiple neurodevelopmental domains at 4 years of age. In Aim 1, we will determine the
association between infant CMV infection and neurodevelopment at 4 years of age. In Aim 2, we will assess the
impact of maternal and infant immune activation and inflammation on child neurodevelopment at 4 years of age.
Lastly, we will conduct mediation analyses to interrogate mechanisms of inflammation and immune activation
leading to neurodevelopmental deficits in HEU and HUU children (Aim 3). These studies will provide a better
understanding of how early-life infections and immunologic insults contribute to long-term child
neurodevelopment and will inform strategic development of interventions to improve neurodevelopmental
outcomes in HEU children.

## Key facts

- **NIH application ID:** 10381037
- **Project number:** 1P01HD107669-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jennifer Ann Slyker
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $892,566
- **Award type:** 1
- **Project period:** 2022-09-09 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10381037

## Citation

> US National Institutes of Health, RePORTER application 10381037, The effect of cytomegalovirus, inflammation, and immune activation on neurodevelopment in children exposed to maternal HIV infection (1P01HD107669-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10381037. Licensed CC0.

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