T-cell activation and exhaustion in the HIV-positive female genital tract

Ended Project Grant Awarded Last action

Award ID
R01HD114505
Recipient
Awarding agency
Obligated
$6,184,334

Award facts

Completion date
Place of performance
Seattle, WA 98195, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
HIV infection is a chronic viral infection that if untreated leads to progressive loss of the CD4 T cell compartment and eventually aids. In addition to loss of HIV-susceptible CD4 T cells, chronic HIV infection is characterized by robust systemic immune activation including B and T cell activation and proliferation and elevated levels of pro-inflammatory molecules. Indeed, the level of immune activation is strongly associated with HIV disease progression. Even upon antiretroviral therapy (art) initiation and viral suppression, chronic HIV infection is associated with dysfunctional circulating immunity rather than a return to immune quiescence. Further, immune activation in mucosal compartments such as the GUT can persist in chronically infected individuals, even with long-term art. This chronic immune activation during HIV infection was first identified largely through study of men with HIV, though more recent studies have suggested that HIV-associated immune activation may manifest differently in women. Given that women are increasingly affected by HIV, with unaids reporting that 53% of people living with HIV are women and girls as of 2020, IT's evident that there is a GAP in our understanding of immune activation and dysfunction in women, particularly within the female genital tract (FGT) mucosa. A few initial studies have suggested that immune activation is elevated in the FGT of women with HIV, and that art does not restore FGT immune status to homeostatic levels within the initial month of treatment. Thus, we propose to comprehensively evaluate immune activation and dysfunction in the FGT in settings of HIV infection with or without viral suppression for up to 24 months. In a well-characterized cohort of women with and without HIV infection in mombasa, kenya, we will test two primary hypotheses: 1) we hypothesize that HIV infection leads to increased immune activation in the FGT that persists after art initiation and viral suppression, and 2) we hypothesize that that chronic and persistent HIV infection leads to exhaustion of mucosal tissue T cells within the FGT. We will advance the prior research by including a more thorough investigation of immune activation including a focus on regulatory T cell (TREG)-mediated immunoregulatory mechanisms, and T cell exhaustion through use of high-throughput single-cell analysis, and we will examine the effects of longer-term viral suppression on immune activation and dysfunction in both the circulation and FGT. This will allow US to better understand how HIV infection may lead to negative FGT health outcomes.

Transactions

Action Obligated Date
Amendment $0
Amendment $1,515,294
Amendment $1,515,294
Amendment $761,722
Amendment $770,346
Amendment $0
Amendment $0
Amendment $810,839
Original award $810,839

Subawards

Subrecipient Amount Awarded
Fred Hutchinson Cancer Center T-cell activation and exhaustion in the HIV-positive female genital tract. $424,394
Fred Hutchinson Cancer Center $424,317
University Of Nairobi T-cell activation and exhaustion in the HIVpositive female genital tract. $38,064
Fred Hutchinson Cancer Center T-cell activation and exhaustion in the HIV-positive female genital tract. $424,387
University Of Nairobi $38,064
Fred Hutchinson Cancer Center $441,605

Quick answers

Who received award R01HD114505?

R01HD114505 was awarded to University Of Washington by National Institute of Child Health and Human Development (National Institutes of Health) on July 5, 2023.

How much is award R01HD114505 worth?

$6,184,334 has been obligated on R01HD114505.

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