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Screening for atherosclerotic vascular disease in HIV-infected children

Award Number: R01HD083042
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: 03/25/2015
PERIOD OF PERFORMANCE END DATE: 02/28/2022

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Screening for atherosclerotic vascular disease in HIV-infected children - ¿ DESCRIPTION (provided by applicant): In South Africa, HIV-infected children in poorer families are often responsible for the parental care of younger (often uninfected) siblings and so any disease events they experience have far-reaching consequences. As in adults, atherosclerosis due to HIV-related chronic inflammation despite adequate viral suppression is a growing concern for children on antiretroviral therapy (ART). Effective lifestyle, diet and therapeutic interventions are available but efficacy is limited unless instituted early in pathogenesis of atherosclerosis. Diagnosis of asymptomatic increased atherosclerosis risk requires effective nationwide surveillance at primary health clinic level. This longitudinal cohort control study intends to quantify excess atherosclerosis risk in HIV-infected children on ART and to generate and validate a low tech screening algorithm to identify affected asymptomatic individuals using simple input variables that can be routinely collected during primary healthcare follow-up. AIM 1 will investigate the magnitude and longitudinal evolution of atherosclerotic vascular disease (AVD) risk in virally-suppressed perinatally-infected children on ART. Aorto-femoral pulse wave velocity (PWV), a measure of arterial elasticity, predicts incident cardiovascular events in asymptomatic adults and is a reliable gold- standard marker of subclinical atherosclerosis. We will compare longitudinal change in PWV Z-score over 5 years in children with and without HIV. PWV in this Primary Cohort will be adjusted for systolic blood pressure, fasting lipids, glucose, BMI, diet and tobacco smoke exposure. AIM 2 will generate a low tech, low cost, scalable diagnostic screening algorithm to detect asymptomatic increased AVD risk (defined as abnormally raised PWV) in a resource limited setting. We will compare various candidate screening tests that are predictive of incident cardiovascular events in adults, with PWV as a gold standard. Measures collected in the Primary Cohort will be used to develop the algorithm. Measures will be repeated in a Validation Cohort of 75 additional pre-pubertal HIV-infected children receiving the national first- line ART regimen in a programmatic setting, who will be recruited in year 3 and followed longitudinally until year 5 to validate the sensitivit and specificity of the algorithm. AIM 3 will investigate whether the circulating biomarkers most strongly predictive of vascular disease in adults correlate with abnormal PWV in virally-suppressed children and are useful for identifying increased AVD risk. Expected outcomes: A simple surveillance tool will enable nurse-driven, low-cost, high-efficacy country-wide surveillance for increased AVD risk in HIV-infected children on ART using widely-available equipment and easily-obtainable skills, facilitating therapeutic intervention early in pathogenesis Ultimately, early intervention will substantially reduce overall AVD burden in adulthood in this high-risk population, preserving their ability to care for the needs of family members and younger siblings.


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: 2022 ( Subtotal = -$654 )
2022	2019	UNIVERSITEIT STELLENBOSCH	ADMINISTRATION BUILDING B, VICTORIA STREET	STELLENBOSCH				ZAF	Child Health and Human Development Extramural Research	000	5	9/21/2022	NON-COMPETING CONTINUATION	-$654
														Subtotal = -$654

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITEIT STELLENBOSCH	ADMINISTRATION BUILDING B, VICTORIA STREET	STELLENBOSCH				ZAF	Child Health and Human Development Extramural Research	000	5	2/18/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $311,364 )
2019	2019	UNIVERSITEIT STELLENBOSCH	VICTORIA STREET	STELLENBOSCH		7600		ZAF	Child Health and Human Development Extramural Research	000	5	2/28/2019	NON-COMPETING CONTINUATION	$311,364
														Subtotal = $311,364

Issue Date FY: 2018 ( Subtotal = $319,363 )
2018	2018	UNIVERSITEIT STELLENBOSCH	VICTORIA STREET	STELLENBOSCH		7600		ZAF	Child Health and Human Development Extramural Research	001	4	5/8/2018	NON-COMPETING CONTINUATION	$31,938
2018	2018	UNIVERSITEIT STELLENBOSCH	VICTORIA STREET	STELLENBOSCH		7600		ZAF	Child Health and Human Development Extramural Research	000	4	3/1/2018	NON-COMPETING CONTINUATION	$287,425
														Subtotal = $319,363

Issue Date FY: 2017 ( Subtotal = $327,548 )
2017	2017	UNIVERSITEIT STELLENBOSCH	VICTORIA STREET	STELLENBOSCH		7600		ZAF	Child Health and Human Development Extramural Research	000	3	2/16/2017	NON-COMPETING CONTINUATION	$327,548
														Subtotal = $327,548

Issue Date FY: 2016 ( Subtotal = $331,979 )
2016	2016	STELLENBOSCH UNIVERSITY	CLINICAL BUILDING	TYGERGBERG				ZAF	Child Health and Human Development Extramural Research	000	2	3/10/2016	NON-COMPETING CONTINUATION	$331,979
														Subtotal = $331,979

Issue Date FY: 2015 ( Subtotal = $344,545 )
2015	2015	STELLENBOSCH UNIVERSITY	CLINICAL BUILDING	TYGERGBERG				ZAF	Child Health and Human Development Extramural Research	000	1	3/25/2015	NEW	$344,545
														Subtotal = $344,545

Grand Total All Awards = $1,634,145

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Screening for atherosclerotic vascular disease in HIV-infected children

Award Number: R01HD083042

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: 03/25/2015

PERIOD OF PERFORMANCE END DATE: 02/28/2022

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