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Characterizing intact proviral HIV-1 reservoir size and determinants of reservoir dynamics in African populations

Award Number: U01AI152151
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Characterizing intact proviral HIV-1 reservoir size and determinants of reservoir dynamics in African populations - Project Summary Antiretroviral treatment is unable to clear HIV-1 infection because a highly stable latent viral reservoir persists in the host. Key areas of interest with respect to HIV-1 eradication strategies include latent reservoir establishment, size and make-up. A considerable amount is now known about these key areas in subtype B-infected American men, yet there remains limited knowledge in the most affected population, subtype C-infected South African women, or in African populations in general. Population differences may exist with respect to reservoir characteristics, and eradication strategies would need to take such differences into account. Characterization of the HIV-1 reservoir in the African context therefore represents a much needed area of attention. This project proposes to firstly address the need for implementation of a high-throughput, accurate reservoir sizing method in South Africa through optimization of the newly developed intact proviral DNA assay (IPDA) for subtype C HIV-1. This method will be applied to more than 200 women from KwaZulu Natal. Reservoir size in these women will be compared to that of individuals from Ugandan and American cohorts using the same assay to evaulate reservoir differences across populations. This project will also investigate a role for the viral factors Nef and the long terminal repeat, which are drivers of immune evasion and gene transcription respectively, in reservoir size and make-up in a subset of these women. Finally, we will explore the contribution of viral variants from the blood and cervix to the long-lived reservoir in these women using Bayesian evolutionary analyses. We hypothesize that Nef-mediated MHC-I downregulation and LTR activity have independent effects on reservoir size and distribution, and these effects differ according to infecting subtype and study population. This project will allow for comparison of reservoir size across populations using a standardized assay and will evaluate determinants of size and kinetics of establishment.


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 = $0 )
2025	2024	UNIVERSITY OF CAPE TOWN	LOVERS WALK	CAPE TOWN				ZAF	Allergy and Infectious Diseases Research	000	5	8/21/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $165,089 )
2024	2024	UNIVERSITY OF CAPE TOWN	LOVERS WALK	CAPE TOWN				ZAF	Allergy and Infectious Diseases Research	000	5	4/9/2024	NON-COMPETING CONTINUATION	$165,089
2024	2024	UNIVERSITY OF CAPE TOWN	LOVERS WALK	CAPE TOWN				ZAF	Allergy and Infectious Diseases Research	001	5	8/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $165,089

Issue Date FY: 2023 ( Subtotal = $174,952 )
2023	2023	UNIVERSITY OF CAPE TOWN	LOVERS WALK	CAPE TOWN				ZAF	Allergy and Infectious Diseases Research	001	4	3/15/2023	NON-COMPETING CONTINUATION	$174,952
2023	2022	UNIVERSITY OF CAPE TOWN	LOVERS WALK	RONDEBOSCH				ZAF	Allergy and Infectious Diseases Research	000	3	2/2/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $174,952

Issue Date FY: 2022 ( Subtotal = $182,181 )
2022	2022	UNIVERSITY OF CAPE TOWN	LOVERS WALK	RONDEBOSCH				ZAF	Allergy and Infectious Diseases Research	002	3	3/31/2022	NON-COMPETING CONTINUATION	$182,181
2022	2021	UNIVERSITY OF CAPE TOWN	LOVERS WALK	RONDEBOSCH				ZAF	Allergy and Infectious Diseases Research	000	2	1/4/2022	NON-COMPETING CONTINUATION	$0
2022	2021	UNIVERSITY OF CAPE TOWN	LOVERS WALK	RONDEBOSCH				ZAF	Allergy and Infectious Diseases Research	001	2	1/25/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $182,181

Issue Date FY: 2021 ( Subtotal = $191,873 )
2021	2021	UNIVERSITY OF CAPE TOWN	LOVERS WALK	RONDEBOSCH				ZAF	Allergy and Infectious Diseases Research	000	2	4/8/2021	NON-COMPETING CONTINUATION	$191,873
														Subtotal = $191,873

Issue Date FY: 2020 ( Subtotal = $199,474 )
2020	2020	UNIVERSITY OF CAPE TOWN	LOVERS WALK	RONDEBOSCH		007700		ZAF	Allergy and Infectious Diseases Research	000	1	4/14/2020	NEW	$199,474
														Subtotal = $199,474

Grand Total All Awards = $913,569

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Characterizing intact proviral HIV-1 reservoir size and determinants of reservoir dynamics in African populations

Award Number: U01AI152151

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 04/15/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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