K43TW012864
Project Grant
Overview
Grant Description
Bifidobacterium infantis supplementation in early life to improve neurodevelopment in infants exposed to HIV - Higher risk of neurodevelopmental delay during early childhood has been reported among infants who are HIV exposed in utero but uninfected (IHEU) compared to their HIV unexposed counterparts, to which both HIV and antiretroviral regimens may contribute.
Similarly, IHEU have found to have altered gut microbiome composition, with decreases in Bifidobacteria abundance, particularly B. infantis, and increased systemic inflammation during the first year of life.
Recent studies found that low abundance of gut Bifidobacteria during early life is associated with increased risk of neurodevelopmental delay during early childhood in at-risk infants.
As early life gut microbiome is also crucial for immune maturation and development of cognitive function, the question arises whether optimization of the gut microbiome during early life would be sufficient to decrease systemic inflammation and improve neurodevelopment among IHEU.
Dr. Happel, a senior research officer at the University of Cape Town with expertise in molecular biology, microbiology and immunology and career development needs in computational biology, biostatistics and epidemiology, will leverage an ongoing randomized, double-blinded trial of oral B. infantis vs. placebo given during the first month of life to 200 IHEU (R01HD109089).
The trial provides rigorously collected clinical and biological data, a sample repository, and the infrastructure to assess neurodevelopment and systemic inflammation in these IHEU to address this hypothesis.
Specific Aim 1: To compare neurodevelopment longitudinally in IHEU randomized to receive B. infantis versus placebo in early life using the culturally adaptable Bayley Scales of Infant and Toddler Development, 4th edition, at 9 and 24 months of age.
Specific Aim 2: To compare systemic inflammation longitudinally in IHEU randomized to receive B. infantis versus placebo in early life by measuring levels of circulating cytokines previously associated with HIV exposure and neurodevelopment at 1 and 9 months of life by Luminex.
Specific Aim 3: To identify microbial and systemic predictors of neurodevelopment in South African infants by integrating bacterial shotgun metagenomics, stool metabolomics, T cell phenotypes, systemic microbial translocation (generated as part of the parent trial) and plasma cytokine data with neurodevelopmental outcome data (generated here) using multiple data driven approaches.
The proposed project will provide critical data to design further interventions of modifiable biological domains among IHEU that may improve neurodevelopmental health of this growing population.
Findings will provide insight into the use of early-life biomarkers as predictors of neurodevelopment during infancy that could subsequently be exploited for diagnostic tool development to identify at-risk infants.
Together, this might ultimately result in decreased morbidity of IHEU, or of other infants whose gut microbiome was disturbed during early life.
This proposal is highly relevant for sub-Saharan Africa, where >25% of infants are HIV-exposed.
Similarly, IHEU have found to have altered gut microbiome composition, with decreases in Bifidobacteria abundance, particularly B. infantis, and increased systemic inflammation during the first year of life.
Recent studies found that low abundance of gut Bifidobacteria during early life is associated with increased risk of neurodevelopmental delay during early childhood in at-risk infants.
As early life gut microbiome is also crucial for immune maturation and development of cognitive function, the question arises whether optimization of the gut microbiome during early life would be sufficient to decrease systemic inflammation and improve neurodevelopment among IHEU.
Dr. Happel, a senior research officer at the University of Cape Town with expertise in molecular biology, microbiology and immunology and career development needs in computational biology, biostatistics and epidemiology, will leverage an ongoing randomized, double-blinded trial of oral B. infantis vs. placebo given during the first month of life to 200 IHEU (R01HD109089).
The trial provides rigorously collected clinical and biological data, a sample repository, and the infrastructure to assess neurodevelopment and systemic inflammation in these IHEU to address this hypothesis.
Specific Aim 1: To compare neurodevelopment longitudinally in IHEU randomized to receive B. infantis versus placebo in early life using the culturally adaptable Bayley Scales of Infant and Toddler Development, 4th edition, at 9 and 24 months of age.
Specific Aim 2: To compare systemic inflammation longitudinally in IHEU randomized to receive B. infantis versus placebo in early life by measuring levels of circulating cytokines previously associated with HIV exposure and neurodevelopment at 1 and 9 months of life by Luminex.
Specific Aim 3: To identify microbial and systemic predictors of neurodevelopment in South African infants by integrating bacterial shotgun metagenomics, stool metabolomics, T cell phenotypes, systemic microbial translocation (generated as part of the parent trial) and plasma cytokine data with neurodevelopmental outcome data (generated here) using multiple data driven approaches.
The proposed project will provide critical data to design further interventions of modifiable biological domains among IHEU that may improve neurodevelopmental health of this growing population.
Findings will provide insight into the use of early-life biomarkers as predictors of neurodevelopment during infancy that could subsequently be exploited for diagnostic tool development to identify at-risk infants.
Together, this might ultimately result in decreased morbidity of IHEU, or of other infants whose gut microbiome was disturbed during early life.
This proposal is highly relevant for sub-Saharan Africa, where >25% of infants are HIV-exposed.
Awardee
Funding Goals
THE JOHN E. FOGARTY INTERNATIONAL CENTER (FIC) SUPPORTS RESEARCH AND RESEARCH TRAINING TO REDUCE DISPARITIES IN GLOBAL HEALTH AND TO FOSTER PARTNERSHIPS BETWEEN U.S. SCIENTISTS AND THEIR COUNTERPARTS ABROAD. FIC SUPPORTS BASIC BIOLOGICAL, BEHAVIORAL, AND SOCIAL SCIENCE RESEARCH, AS WELL AS RELATED RESEARCH TRAINING AND CAREER DEVELOPMENT. THE RESEARCH PORTFOLIO IS DIVIDED INTO SEVERAL PROGRAMS THAT SUPPORT A WIDE VARIETY OF FUNDING MECHANISMS TO MEET PROGRAMMATIC OBJECTIVES.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
South Africa
Geographic Scope
Foreign
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 307% from $50,000 to $203,524.
University Of Cape Town was awarded
B. infantis Supplementation Neurodevelopment in HIV-Exposed Infants
Project Grant K43TW012864
worth $203,524
from Fogarty International Center in September 2024 with work to be completed primarily in South Africa.
The grant
has a duration of 5 years and
was awarded through assistance program 93.989 International Research and Research Training.
The Project Grant was awarded through grant opportunity Emerging Global Leader Award (K43 Independent Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 9/5/25
Period of Performance
9/1/24
Start Date
8/31/29
End Date
Funding Split
$203.5K
Federal Obligation
$0.0
Non-Federal Obligation
$203.5K
Total Obligated
Activity Timeline
Transaction History
Modifications to K43TW012864
Additional Detail
Award ID FAIN
K43TW012864
SAI Number
K43TW012864-1253739941
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NF00 NIH Fogarty International Center
Funding Office
75NF00 NIH Fogarty International Center
Awardee UEI
NN5NML6VUCF9
Awardee CAGE
SBH72
Performance District
Not Applicable
Modified: 9/5/25