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

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $770,346

## Abstract

Project Summary
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.

## Key facts

- **NIH application ID:** 10881997
- **Project number:** 5R01HD114505-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jennifer M Lund
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $770,346
- **Award type:** 5
- **Project period:** 2023-07-05 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881997

## Citation

> US National Institutes of Health, RePORTER application 10881997, T-cell activation and exhaustion in the HIV-positive female genital tract (5R01HD114505-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10881997. Licensed CC0.

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