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Viral and Host Determinants of Cognitive Status in Vertically Transmitted HIV

Award Number: R01MH108559
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/22/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2023

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Viral and Host Determinants of Cognitive Status in Vertically Transmitted HIV - PROJECT SUMMARY-ABSTRACT The purpose of the proposed study is conduct a controlled investigation of HIV host and viral dynamics on brain integrity in vertically infected children on stable combined antiretroviral therapy (cART) in Myanmar. Outcomes from the PREDICT trial in Southeast Asia revealed residual cognitive impairment among pediatric HIV+ individuals with vertical infection. Socioeconomic variables predicted cognitive test performance among infected children and children exposed to HIV but uninfected with the virus. Efforts to define the neuropathogenesis of HIV require adequate control of these environmental variables known to influence cognitive test performance and engagement in ADLs. The majority of HIV+ children in Myanmar reside in privately funded orphanages with standardized caregiver status, nutrition, and education. Our preliminary work reveals cognitive impairment in these children on cART with high CD4 count when compared to demographically matched healthy controls (HIV-). Further, 40% of the HIV+ children express preferential use of the CXCR4 co-receptor and the degree of cognitive impairment is greater among these children compared to those expressing the CCR5 co-receptor despite similar CD4 counts. Previous studies have associated CXCR4 utilization with worse cognition in HIV+ adults with advanced disease, but it is unclear from these studies if co-receptor subtype is liked to cognitive impairment or more simply a correlated variable between disease severity and cognitive impairment. Our preliminary data suggests a mechanistic role for CXCR4 on reduced brain integrity independent of advanced disease, emphasizing the need to identify the relevant immunological factors. Work from our team previously demonstrated that circulating monocyte HIV content, monocyte subpopulations, and myeloid-derived immunological mediators are key mechanisms of HIV-associated neurocognitive impairment. The present study will examine these immunological mechanisms and co-receptor tropism in the cascade of events related to cognitive impairment in vertically infected youth. This information is critical to facilitate the development of targeted treatments to improve cognitive function among children with vertically infected HIV. We will enroll 120 HIV+ vertically infected children and adolescents between the ages of 8 and 15 and 60 HIV- controls matched for demographics, and all residing in privately funded orphanages. Neuropsychological, virological, and immunological assays will be completed to determine pediatric HIV neuropathogenesis in the context of stable cART.


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: 2024 ( Subtotal = -$21,443 )
2024	2021	UNIVERSITY OF MISSOURI SYSTEM	1 UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	000	5	2/2/2024	NON-COMPETING CONTINUATION	-$21,443
														Subtotal = -$21,443

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF MISSOURI SYSTEM	ONE UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	000	5	2/3/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $645,454 )
2021	2021	UNIVERSITY OF MISSOURI SYSTEM	ONE UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	000	5	1/25/2021	NON-COMPETING CONTINUATION	$645,454
														Subtotal = $645,454

Issue Date FY: 2020 ( Subtotal = $646,278 )
2020	2020	UNIVERSITY OF MISSOURI SYSTEM	ONE UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	001	4	2/5/2020	NON-COMPETING CONTINUATION	$64,629
2020	2020	UNIVERSITY OF MISSOURI SYSTEM	ONE UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	000	4	12/18/2019	NON-COMPETING CONTINUATION	$581,649
														Subtotal = $646,278

Issue Date FY: 2019 ( Subtotal = $663,299 )
2019	2019	UNIVERSITY OF MISSOURI SYSTEM	ONE UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	000	3	11/15/2018	NON-COMPETING CONTINUATION	$663,299
														Subtotal = $663,299

Issue Date FY: 2018 ( Subtotal = $668,983 )
2018	2018	UNIVERSITY OF MISSOURI SYSTEM	ONE UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	000	2	11/29/2017	NON-COMPETING CONTINUATION	$602,084
2018	2018	UNIVERSITY OF MISSOURI SYSTEM	ONE UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	001	2	6/6/2018	NON-COMPETING CONTINUATION	$66,899
														Subtotal = $668,983

Issue Date FY: 2017 ( Subtotal = $729,942 )
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	ONE UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	001	1	9/26/2017	NEW	$66,278
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	ONE UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	002	1	9/27/2017	NEW	$0
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	ONE UNIVERSITY BLVD	SAINT LOUIS	MO	63121	SAINT LOUIS	USA	Mental Health Research Grants	000	1	12/20/2016	NEW	$663,664
														Subtotal = $729,942

Grand Total All Awards = $3,332,513

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Viral and Host Determinants of Cognitive Status in Vertically Transmitted HIV

Award Number: R01MH108559

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/22/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2023

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