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Early life determinants of cardiometabolic health from birth to adolescence amongst HIV-exposed and unexposed South African children

Award Number: R01HD108048
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/18/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Early life determinants of cardiometabolic health from birth to adolescence amongst HIV-exposed and unexposed South African children - PROJECT ABSTRACT: Despite not living with HIV, HIV-exposed but uninfected (HEU) children experience higher levels of morbidity and mortality in childhood and have worse cardiometabolic outcomes, compared to HIV-unexposed (HU) children. HEU children have suboptimal immune development in early life. This increases their risk for comorbid infections in childhood, and may exacerbate cardiometabolic risk by leading to increased systemic inflammation that adversely impacts metabolic pathways. Our group has used metabolomics to characterize metabolic dysfunction starting in early life and have identified early life infections as a driver of systemic inflammation and the development of pro-atherogenic metabolic profiles in childhood. Thus, the higher burden of infections in early life among HEU children may represent and important and unexplored pathway in the pathogenesis of cardiometabolic dysfunction. In this proposal, we leverage the Drakenstein Child Health Study, a well- characterized cohort of HEU and HU participants followed from birth, to investigate how HIV-exposure and early life infections affect inflammatory response changes to the metabolome from birth to early adolescence, and evaluate how these changes influence the development of adverse cardiometabolic outcomes in early adolescence. Aim 1 will characterize longitudinal metabolomic trajectories from infancy to early adolescence using 250 metabolites among HEU (n=244) and HU (n=735) children over different developmental stages. Aim 2 will develop a set of predictive models to identify metabolomic profiles in childhood (1 and 5 years) that predict cardiometabolic dysfunction, including higher BMI/adiposity, arterial stiffness, blood pressure, dyslipidemia, and insulin resistance, in early adolescence (10 years). Aim 3 will evaluate if relationships between early life infection burden and metabolomic profiles at 10 years of age are mediated by inflammatory pathways, overall and by HIV exposure status. The proposed study will make significant contributions to the field of HIV by providing some of the first longitudinal metabolomic data from a population-based cohort of HEU and HU participants to elucidate the molecular pathways underlying the development of cardiometabolic dysfunction starting in infancy. In addition, findings from this proposal have direct clinical relevance by identifying metabolic and inflammatory biomarkers in early life to support cardiometabolic risk stratification and inform whether future intervention efforts to address cardiometabolic health in HEU should include reducing infection burden or severity. Taken together, this work will provide novel mechanistic data and biomarker identification that will inform whether HEU should be targeted for screening and intervention efforts in childhood to reduce their risk of cardiometabolic disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $173,638 )
2025	2025	HARTFORD HOSPITAL	80 SEYMOUR ST	HARTFORD	CT	06106	CAPITOL	USA	Child Health and Human Development Extramural Research	001	4	9/2/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$173,638
2025	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Child Health and Human Development Extramural Research	000	3	9/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $173,638

Issue Date FY: 2024 ( Subtotal = $546,543 )
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Child Health and Human Development Extramural Research	000	3	7/17/2024	NON-COMPETING CONTINUATION	$541,078
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Child Health and Human Development Extramural Research	001	3	8/12/2024	NON-COMPETING CONTINUATION	$5,465
														Subtotal = $546,543

Issue Date FY: 2023 ( Subtotal = $583,363 )
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Child Health and Human Development Extramural Research	000	2	7/13/2023	NON-COMPETING CONTINUATION	$583,363
														Subtotal = $583,363

Issue Date FY: 2022 ( Subtotal = $622,025 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Child Health and Human Development Extramural Research	000	1	8/18/2022	NEW	$622,025
														Subtotal = $622,025

Grand Total All Awards = $1,925,569

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Early life determinants of cardiometabolic health from birth to adolescence amongst HIV-exposed and unexposed South African children

Award Number: R01HD108048

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/18/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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