# Understanding the rectal mucosal effects of cross-sex hormone therapy among US and Thai transgender women

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $680,609

## Abstract

PROJECT SUMMARY
Until recently, the specific HIV prevention needs of transgender populations received insufficient attention, and
the biology of HIV transmission, specifically, has been understudied to date. Transgender women who have
sex with men (TGWSM) are at elevated risk for HIV acquisition with global HIV prevalence rates approximately
20% and odds of infection 48 times the general population. Engaging in condomless receptive anal intercourse
(CRAI) is common among TGWSM, and the physiologic efficiency of HIV transmission across the rectal
mucosa facilitates HIV transmission. Historically, TGWSM have been grouped with men who have sex with
men (MSM) in HIV prevention studies due to presumed similar risks of rectal HIV exposure despite their unique
psychosocial, biologic, and prevention needs. From a biologic perspective, many TGWSM use cross-sex
hormone therapy with uncertain rectal mucosal effects. The effects of endogenous and exogenous hormones
in the human and animal-model female genital tract has been described with estrogen generally being seen as
hindering HIV transmission and progesterone facilitating transmission; however, few studies report effects on
the rectal mucosa. In addition, the intestinal mucosa is known to be steroidogenic, and colonic epithelial cells
express estrogen receptor β, suggesting that exogenous hormone therapy likely has an effect on the rectal
mucosa that could influence HIV transmission. In this application, we will build upon our successful
translational mucosal immunology program with a highly successful clinical research and retention
infrastructure that was designed to understand factors that may influence rectal HIV transmission and propose
to examine the effects of cross-sex hormone therapy on the rectal mucosal resident cellular populations,
transcriptome, and microbiome in TGWSM. In addition, we will capitalize on the existing infrastructure of the
Emory/CDC HIV/AIDS Clinical Trials Unit and expand our studies to an international site, Bangkok, in order to
make global comparisons in our findings. In aim 1, we will compare HIV target cell availability in 1) TGWSM on
estrogen therapy, 2) TGWSM on estrogen + progesterone therapy, and 3) cisgender MSM. We will also
examine HIV target cell availability in TGWSM before and after initiating cross-sex hormone therapy in a
longitudinal cohort. In aim 2, we will compare the transcriptome by RNA-seq between groups in the cross-
sectional cohort and before and after initiating cross-sex hormone therapy in the longitudinal cohort in order to
identify new targets for biomedical HIV prevention interventions. Finally, in aim 3, we will define the differences
in the rectal mucosal microbiota associated with cross-sex hormone therapy in order to inform the design of
future HIV prevention intervention clinical trials. The overarching goal of this proposal is to achieve a better
understanding of the rectal mucosal effects of cross-sex hormones that will allow for the o...

## Key facts

- **NIH application ID:** 10447095
- **Project number:** 5R01AI147839-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Colleen F Kelley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $680,609
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447095

## Citation

> US National Institutes of Health, RePORTER application 10447095, Understanding the rectal mucosal effects of cross-sex hormone therapy among US and Thai transgender women (5R01AI147839-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10447095. Licensed CC0.

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