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Altered mitochondrial function and HIV-associatedcardiometabolic disease in populations from South Africa and Kenya (MITO-SAKen)

Award Number: R21TW012358
ORGANIZATION: FOGARTY INTERNATIONAL CENTER
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/12/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Altered mitochondrial function and HIV-associatedcardiometabolic disease in populations from South Africa and Kenya (MITO-SAKen) - PROJECT SUMMARY Current evidence suggests that sub-Saharan Africa is facing a double burden of disease, with HIV and cardi- ometabolic disease seemingly on a collision course. This is compounded by the growing burden of cardiometa- bolic disease attributable to HIV, which will further impact already struggling public health resources in the region. The relative lack of epidemiological and mechanistic studies on the intersection between HIV and cardiometa- bolic disease in sub-Saharan African populations therefore represents a major knowledge gap. Several factors, including mitochondrial dysfunction, are implicated in the pathogenesis of HIV-associated cardiometabolic dis- ease. Mitochondrial dysfunction has been linked to both HIV and cardiometabolic disease and previous studies have demonstrated mitochondrial involvement in several cardiometabolic-related pathologies in people living with HIV (PLWH). Whilst a common underlying mechanism of HIV-associated cardiometabolic disease remains elusive, mitochondrial dysfunction may uniquely drive the pathogenesis of cardiometabolic disease to a greater extent in people with compared to without HIV. PLWH in sub-Saharan Africa are particularly susceptible to mi- tochondrial dysfunction due to a unique convergence of intrinsic and extrinsic risk factors, including exposure to endemic pathogens and high levels of inflammation. In this study, it is hypothesized that antiretroviral therapy (ART)-experienced PLWH with cardiometabolic disease in sub-Saharan Africa will show greater mitochondrial dysfunction compared to PLWH without cardiometabolic disease and controls without HIV. The hypothesis will be tested in an exploratory, cross-sectional study comprising cohorts in South Africa and Kenya. In Specific Aim 1, mitochondrial respiratory function (measured by state-of-the-art high resolution respirometry and fluorometry technology) will be compared in participants with and without HIV, and it will be determined whether mitochon- drial dysfunction is more pronounced in PLWH with cardiometabolic disease. In Specific Aim 2, mRNA expres- sion of genes linked to mitochondrial function and dynamics will be compared in participants with and without HIV, and it will be determined whether gene expression is different in PLWH with cardiometabolic disease. Re- lated pathophysiological processes, including inflammatory, immunological and endocrine, will be measured to complement the mitochondrial function and gene expression experiments in Aims 1 and 2. This exploratory study will provide preliminary evidence that heightened mitochondrial dysfunction is present in PLWH with cardiomet- abolic disease from South Africa and Kenya. These results may benefit public health in the region, including screening of PLWH at risk of mitochondrial dysfunction, revision of 1st line ART that includes drugs with mito- chondrial toxicity, and stronger emphasis on cardiometabolic disease in PLWH. New research networks in South Africa, Kenya and the US will be forged, with a strong capacity development focus.


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: 2026 ( Subtotal = -$22,143 )
2026	2023	STELLENBOSCH UNIVERSITY	ADMINISTRATION BUILDING B, VICTORIA ST	STELLENBOSCH				ZAF	International Research and Research Training	000	2	12/4/2025	NON-COMPETING CONTINUATION	-$22,143
														Subtotal = -$22,143

Issue Date FY: 2023 ( Subtotal = $154,156 )
2023	2023	UNIVERSITEIT STELLENBOSCH	ADMINISTRATION BUILDING B, VICTORIA STREET	STELLENBOSCH				ZAF	International Research and Research Training	001	2	6/26/2023	NON-COMPETING CONTINUATION	$154,156
2023	2022	UNIVERSITEIT STELLENBOSCH	ADMINISTRATION BUILDING B, VICTORIA STREET	STELLENBOSCH				ZAF	International Research and Research Training	000	1	3/20/2023	NEW	$0
														Subtotal = $154,156

Issue Date FY: 2022 ( Subtotal = $144,594 )
2022	2022	UNIVERSITEIT STELLENBOSCH	ADMINISTRATION BUILDING B, VICTORIA STREET	STELLENBOSCH				ZAF	International Research and Research Training	000	1	9/12/2022	NEW	$144,594
														Subtotal = $144,594

Grand Total All Awards = $276,607

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Altered mitochondrial function and HIV-associatedcardiometabolic disease in populations from South Africa and Kenya (MITO-SAKen)

Award Number: R21TW012358

ORGANIZATION: FOGARTY INTERNATIONAL CENTER

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/12/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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