# The impact of in utero HIV exposure on infant T and B cell responses in Malawi

> **NIH NIH U01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $433,033

## Abstract

Project Summary
More than 1.5 million infants each year are born with in utero exposure to HIV infection. While prevention of
mother to child transmission successfully prevents congenital infection, HIV exposed but uninfected infants
(HEU) are more susceptible to common enteric and respiratory infections than their unexposed counterparts,
and have higher mortality rate. The precise immunologic alterations that are responsible for this phenomenon
among HEU infants have never been clearly characterized. Studies conducted after widespread availability of
antiretroviral therapy (ART) have shown less pronounced differences in morbidity and mortality between HIV
exposed and unexposed infants. We believe that the immune perturbations associated with in utero HIV
exposure are mitigated by effective ART and the longer the control of the HIV infection is during gestation, the
less immune alterations and clinical risk of disease the infant will experience. In this study, we will test the
hypothesis that infants born to mothers with suppressed HIV infection since conception will have adaptive
immune responses similar to HIV-unexposed infants while infants exposed to high level of HIV infection
through most of pregnancy will have a dysregulated adaptive immune response. We propose a longitudinal
analysis of adaptive immune subsets in HEU infants, comparing three well-characterized mother-infant cohorts
from a single health center in Malawi, where, as in much of sub-Saharan Africa, women often receive their first
HIV diagnosis when they present for antenatal care late in pregnancy. In this setting, we will enroll (1) infants
born to women diagnosed with HIV infection at the first antenatal visit after 26 weeks gestation, thus exposed
to uncontrolled viremia for over half of the pregnancy, (2) infants born to women on ART with undetectable viral
loads before conception, and (3) HIV unexposed infants born to HIV uninfected mothers. All HIV-infected
women will receive the same ART regimen and will breastfeed their infants during the 9-month follow up
period. We will assess the adaptive immune response by probing the immune system at birth, 4 and 9 months
of age with both polyclonal stimuli and routine immunization antigens, to which all infants will be exposed in the
first three months of life. We will compare differentiation, activation levels and antigen specific T and B cell
responses for the three groups of infants, applying state-of-the-art technology for detailed and comprehensive
analyses. This will be the most comprehensive longitudinal assessment of the impact of HIV exposure on the
development of the adaptive immune responses in infants. The results will provide important evidence for
public health policy in helping to determine the optimal timing of ART treatment to maximize infant health and
survival.

## Key facts

- **NIH application ID:** 10165763
- **Project number:** 5U01HD092308-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Cristiana Cairo
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $433,033
- **Award type:** 5
- **Project period:** 2017-06-07 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165763

## Citation

> US National Institutes of Health, RePORTER application 10165763, The impact of in utero HIV exposure on infant T and B cell responses in Malawi (5U01HD092308-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10165763. Licensed CC0.

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