# Trial of Human Milk Oligosaccharide-based synbiotics for HIV-exposed uninfected children

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $732,299

## Abstract

Project Summary
HIV-exposed uninfected (HEU) infants have higher rates of mortality, infectious morbidity and growth deficits
compared to HIV-unexposed uninfected (HUU) infants despite the success of maternal antiretroviral therapy
(ART) in reducing vertical transmission. Our group has observed that human milk oligosaccharide (HMO)
composition of breastmilk, and its relationships to the infant gut microbiome maturity and composition, may
account for some of the increased risks seen in HEU infants. Currently, no specific interventions have been
shown to correct for disparities in health outcomes experienced by HEU infants. To address this gap, we
propose a proof-of-concept, randomized, placebo-controlled trial of a synbiotic in breast-fed HEU infants. The
synbiotic is composed of 2'-fucosyllactose (2'FL) HMO and B. infantis probiotic. 2'FL is associated with
reductions in mortality, infectious morbidity and growth deficits. B. infantis is included to support 2'FL
fermentation and thereby maximize benefits from the 2'FL intervention. We will randomize 120 breast-fed HEU
infants at 4 weeks of age 1:1 to receive synbiotic or placebo through 24 weeks of age, with a follow-up through
48 weeks of age. We will also recruit 60 breast-fed HUU infants as a comparator group and they will be
followed for the same duration with no intervention. This study will be conducted in rural South Africa, in a
region with high maternal HIV prevalence and high rates of infectious morbidity and growth deficits in infants.
In specific aim 1, we will evaluate whether the synbiotic i) reduces infectious morbidity and growth faltering,
and ii) influences biological pathways related to infant gut microbiome, metabolism, and inflammation while the
intervention is in place during the first 24 weeks of age. In specific aim 2, we will evaluate whether effects
persist after the intervention is discontinued through 48 weeks of age. Specific aim 3 will compare HEU and
HUU cohorts and investigate biological pathways associated with infectious morbidity and growth. Overall, we
hypothesize that the synbiotic will reduce infectious morbidity and improve growth in HEU infants. Our study
will provide novel information on whether some of the excess risks in HEU infants can be ameliorated through
interventions targeting breastfeeding-mediated microbiome and inflammatory pathways.

## Key facts

- **NIH application ID:** 10857315
- **Project number:** 5R01HD105492-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Rupak Shivakoti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $732,299
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10857315

## Citation

> US National Institutes of Health, RePORTER application 10857315, Trial of Human Milk Oligosaccharide-based synbiotics for HIV-exposed uninfected children (5R01HD105492-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10857315. Licensed CC0.

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