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Targeting the HIV-1 Reservoir in Myeloid Cells

Award Number: R01MH127979
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/06/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Targeting the HIV-1 Reservoir in Myeloid Cells - ABSTRACT HIV is reverse-transcribed and integrated into the DNA of host cells, resulting in persistent infections that are difficult to clear. To date, there is no effective cure to clear the virus from HIV- infected patients. We have shown an approach to eradicate HIV infections by selective elimination of host cells harboring replication-competent HIV (SECH). The SECH treatment can clear HIV-1 in over 50% mice reconstituted with a human immune system, and in blood samples from HIV-1- infected patients. SECH can clear HIV-infection not only in CD4 T cells, but also in macrophages and microglia cells. Experiments are proposed to determine how to improve the efficacy and safety for SECH in clearing HIV-infection in the macrophage lineage: 1) To improve the efficacy and specificity in the killing of HIV-1-infected macrophages. We have found that increased viral reactivation leads to improved viral clearance in humanized mice. We will identify drugs that show greater potentials in virus reactivation that could lead to better HIV clearance. We will examine the inflammatory potentials for IDB and alternative LRAs in macrophages, and determine what inflammatory cytokines may need to be targeted; 2) To determine how to improve the efficacy and safety in the clearance of HIV reservoir in the macrophage lineage in lymphoid organs and in the brain of humanized mice. We will evaluate whether alternative agents can improve the clearance of HIV-1 in humanized mice in vivo. We will also determine whether optimum SECH regimens can induce limited and controllable inflammatory responses. Our proposed work will provide novel insights into how targeting apoptosis and autophagy regulates the clearance of HIV infection in the macrophage lineage. The studies will facilitate the development of SECH clear HIV-1 infection in lymphoid organs and in the brain to achieve complete eradication of HIV-1.


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 = $0 )
2026	2025	THE METHODIST HOSPITAL RESEARCH INSTITUTE	6565 FANNIN ST STE D200	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	000	5	3/24/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $483,639 )
2025	2025	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	001	5	9/23/2025	NON-COMPETING CONTINUATION	$72,546
2025	2025	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	000	5	5/2/2025	NON-COMPETING CONTINUATION	$411,093
														Subtotal = $483,639

Issue Date FY: 2024 ( Subtotal = $483,639 )
2024	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	000	4	6/11/2024	NON-COMPETING CONTINUATION	$483,639
														Subtotal = $483,639

Issue Date FY: 2023 ( Subtotal = $483,639 )
2023	2023	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	000	3	5/11/2023	NON-COMPETING CONTINUATION	$483,639
														Subtotal = $483,639

Issue Date FY: 2022 ( Subtotal = $483,639 )
2022	2022	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	001	2	6/6/2022	NON-COMPETING CONTINUATION	$483,639
2022	2021	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	000	1	11/10/2021	NEW	$0
														Subtotal = $483,639

Issue Date FY: 2021 ( Subtotal = $483,639 )
2021	2021	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	000	1	7/6/2021	NEW	$483,639
														Subtotal = $483,639

Grand Total All Awards = $2,418,195

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Targeting the HIV-1 Reservoir in Myeloid Cells

Award Number: R01MH127979

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/06/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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