# Sex, Gender and the Immunopathogenesis of HIV

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $543,058

## Abstract

Project Summary
Biological sex is associated with clear differences in HIV immunopathogenesis, but there is limited understanding
of the mechanisms of this variation. There are 19.1 million women and girls living with HIV infection, accounting
for slightly more than half of the people living with HIV globally, but women are generally a minority of study
participants and sex-stratified analyses are uncommon. Transgender women bear a disproportionate burden of
infection, and even fewer studies have sought to understand the biological impact of female gender identity on
HIV infection outcomes. Studies of sex and gender differences in the mechanistic pathways driving immune
responses to infection, pathologic inflammation and control of the HIV reservoir are critical to the development
of novel therapeutic interventions. In this proposal, we investigate both biological sex and female gender identity
to disentangle their contributions to immune pathology. Specifically, we will work with the extensive genomic and
clinical data in the International Collaboration for the Genomics of HIV (ICGH) dataset to analyze genetic
determinants of HIV disease progression on the sex chromosomes and in a sex stratified analysis of the
autosomes. We will also work with the Transcendendo cohort in Brazil, a cohort designed with community input
to follow individuals assigned a male sex at birth and living with a female gender. We will design groups for the
collection of biospecimens from cohort participants selected based on differing use of gender-affirming hormone
therapy, HIV infection status, and accounting for critical covariates including trauma and depression. With
immune transcriptional profiling, we will assess the impact of gender identity on immune activation profiles, to
inform the understanding of the unique contributions of chromosomal sex, hormone use and lived gender identity.
Finally, we will specifically test the sex-differential impact of estrogen signaling on T cell activation and HIV
latency reversal, building on our prior studies identifying sex specific characteristics of the HIV latent reservoir.
Combined these studies, will provide novel insights into the impact of both sex and gender on the immune
response to HIV infection.

## Key facts

- **NIH application ID:** 10214530
- **Project number:** 5R01AI154541-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Eileen Patricia Scully
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $543,058
- **Award type:** 5
- **Project period:** 2020-07-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214530

## Citation

> US National Institutes of Health, RePORTER application 10214530, Sex, Gender and the Immunopathogenesis of HIV (5R01AI154541-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10214530. Licensed CC0.

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