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Identification of the HIV Reservoir in Lymph Nodes Using Single Cell RNA-Seq

Award Number: R01AI138546
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Identification of the HIV Reservoir in Lymph Nodes Using Single Cell RNA-Seq - MODIFIED PROJECT SUMMARY HIV persistence in the face of antiretroviral therapy (ART) necessitates lifelong treatment of infected individuals because of a reservoir of HIV infected cells. The Covid-19 pandemic has resulted in the critical need to better understand the interaction between HIV and SARS-CoV-2. Our preliminary data indicates that poorly controlled HIV infection leads to prolonged SARS-CoV-2 infection which evolves variant-like mutations. It also interferes with the neutralizing antibody response elicited by Covid-19 vaccines. As there is no sign that SARS-CoV-2 will be eliminated anytime soon, these questions are critical for both the health of people living with HIV and possibly to prevent continued emergence of SARS-CoV-2 variants. MODIFIED ABSTRACT HIV infection is currently lifelong due to the persistence of the infection in the face of ART because of a reservoir of HIV infected cells which is insensitive to antiretroviral drugs [1]. South Africa has a high proportion of people living with HIV (PLWH), with about one-third of the population in the Durban area being PLWH [2, 3]. Due Covid-19 and other factors, many individuals are not fully suppressed with ART and about 10% of PLWH in our Durban based cohort of confirmed SARS-CoV-2 infected cases have long-term unsuppressed HIV infection culminating in advanced HIV disease [2]. Incomplete suppression of HIV replication would lead to HIV reservoirs being replenished and maintained by ongoing HIV replication [1]. Furthermore, it may compromise immune responses to SARS-CoV-2 [4, 5]. This leads to long-term SARS-CoV-2 infection which we and others have found to evolve neutralizing antibody escape mutations in the SARS-CoV-2 spike protein [6]. Such evolution may form variants. In addition to causing prolonged SARS-CoV-2 infection, we have preliminary data showing that mRNA vaccines do not elicit an effective neutralizing immune response in PLWH with poorly suppressed HIV infection. There may also be unknown consequences to HIV reservoirs and the ability of ART to suppress the HIV reservoir in different anatomical compartments if SARS-CoV-2 infection is long and causes extensive immune activation. Given these unexpected developments which are the consequence of the Covid-19 pandemic, we propose to modify the current study Aims to understand the impact of HIV status and level of suppression on the immune response to SARS-CoV-2 infection and vaccines, as well as determine the effect of long-term SARS-CoV-2 infection on HIV reservoir suppression.


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 = -$1,769 )
2025	2022	AFRICA HEALTH RESEARCH INSTITUTE	719 UMBILO RD	DURBAN				ZAF	Allergy and Infectious Diseases Research	000	5	6/25/2025	NON-COMPETING CONTINUATION	-$1,769
														Subtotal = -$1,769

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	AFRICA HEALTH RESEARCH INSTITUTE	719 UMBILO RD	DURBAN				ZAF	Allergy and Infectious Diseases Research	000	5	3/18/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	KWAZULU NATAL RESEARCH INSTITUTE FOR TUBERCULOSIS AND HIV (K-RITH)	UKZN UMBILO ROAD	DURBAN				ZAF	Allergy and Infectious Diseases Research	000	5	11/17/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $141,941 )
2022	2022	KWAZULU NATAL RESEARCH INSTITUTE FOR TUBERCULOSIS AND HIV (K-RITH)	UKZN UMBILO ROAD	DURBAN				ZAF	Allergy and Infectious Diseases Research	000	5	1/14/2022	NON-COMPETING CONTINUATION	$141,941
														Subtotal = $141,941

Issue Date FY: 2021 ( Subtotal = $142,937 )
2021	2021	KWAZULU NATAL RESEARCH INSTITUTE FOR TUBERCULOSIS AND HIV (K-RITH)	UKZN UMBILO ROAD	DURBAN				ZAF	Allergy and Infectious Diseases Research	000	4	1/25/2021	NON-COMPETING CONTINUATION	$142,937
														Subtotal = $142,937

Issue Date FY: 2020 ( Subtotal = $143,898 )
2020	2020	KWAZULU NATAL RESEARCH INSTITUTE FOR TUBERCULOSIS AND HIV (K-RITH)	UKZN UMBILO ROAD	DURBAN		4001		ZAF	Allergy and Infectious Diseases Research	000	3	1/22/2020	NON-COMPETING CONTINUATION	$143,898
														Subtotal = $143,898

Issue Date FY: 2019 ( Subtotal = $144,822 )
2019	2019	KWAZULU NATAL RESEARCH INSTITUTE FOR TUBERCULOSIS AND HIV (K-RITH)	UKZN UMBILO ROAD	DURBAN		4001		ZAF	Allergy and Infectious Diseases Research	000	2	1/11/2019	NON-COMPETING CONTINUATION	$144,822
2019	2019	KWAZULU NATAL RESEARCH INSTITUTE FOR TUBERCULOSIS AND HIV (K-RITH)	UKZN UMBILO ROAD	DURBAN		4001		ZAF	Allergy and Infectious Diseases Research	002	2	7/19/2019	NON-COMPETING CONTINUATION	$0
2019	2018	KWAZULU NATAL RESEARCH INSTITUTE FOR TUBERCULOSIS AND HIV (K-RITH)	UKZN UMBILO ROAD	DURBAN		4001		ZAF	Allergy and Infectious Diseases Research	001	1	7/19/2019	NEW	$0
														Subtotal = $144,822

Issue Date FY: 2018 ( Subtotal = $147,711 )
2018	2018	KWAZULU NATAL RESEARCH INSTITUTE FOR TUBERCULOSIS AND HIV (K-RITH)	UKZN UMBILO ROAD	DURBAN		4001		ZAF	Allergy and Infectious Diseases Research	000	1	2/12/2018	NEW	$147,711
														Subtotal = $147,711

Grand Total All Awards = $719,540

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Identification of the HIV Reservoir in Lymph Nodes Using Single Cell RNA-Seq

Award Number: R01AI138546

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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