Feminizing Hormone Therapy and the Rectal Mucosa Immune Environment in Transgender Women
- Registration Number
- NCT04531943
- Lead Sponsor
- Emory University
- Brief Summary
The overarching goal of this research study is to achieve a better understanding of the rectal mucosal effects of feminizing hormones in people assigned male sex at birth and currently taking feminizing hormones who have sex with men. Better understanding the rectal mucosa in this population will allow for the optimization of current biomedical HIV prevention interventions and enhance design of future interventions, including an effective HIV vaccine. This study will recruit approximately 520 transgender women who have receptive anal intercourse with men (TGWSM) and cis-gender men into one of two cohorts. Cohort 1 is a cross-sectional study and Cohort 2 is a longitudinal study; enrollment into each cohort is based on participant characteristics.
- Detailed Description
Transgender women who have receptive anal intercourse with men (TGWSM; assigned male sex at birth and taking/planning to take feminizing hormone therapy) are at high risk of HIV, and many HIV infections occur due to exposure to the rectal mucosa. In this study, the researchers will examine the biologic effects of feminizing hormone therapy on the mucosal immune milieu of the rectum. A better understanding of rectal HIV transmission among TGWSM will lead to the development of improved biomedical prevention interventions.
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 feminizing 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. For this project, the researchers 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 feminizing hormone therapy on the rectal mucosal resident cellular populations, transcriptome, and microbiome in TGWSM. In the rectal mucosa, the researchers will compare HIV target cell availability, the transcriptome, and microbiome in a cross-sectional cohort of 1) TGWSM on using feminizing hormone therapy (n=300) and 2) cisgender MSM (n=150). The researchers will also examine HIV target cell availability, the transcriptome, and microbiome in a longitudinal study of TGWSM (n=70) before and after initiating feminizing hormone therapy.
Two cohorts of HIV-negative TGWSM will be enrolled in this study. Cohort 1 will be a cross-sectional study where the researchers will enroll 300 TGWSM who are on feminizing hormone therapy and a control group of 150 sexually active cisgender men (assigned male sex at birth and currently identify as male) who have sex with men. Individuals in Cohort 1 will participate in study activities for up to 12 weeks. Cohort 2 is a longitudinal study where 70 TGWSM who are naïve to feminizing hormone therapy or have not taken feminizing hormone therapy for \> 6 months and plan to initiate feminizing hormone therapy will be enrolled. Individuals in Cohort 2 will participate in study activities for 18 months.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 520
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description TGWSM Using Estrogen Estrogen Cohort 1 participants are in the cross-sectional study and will attend two study visits, participating in study activities for up to 12 weeks. Blood samples and rectal mucosal samples will be obtained. This group of participants in Cohort 1 consists of TGWSM currently using feminizing hormone therapy consisting of only estrogen. TGWSM Initiating Feminizing Hormone Therapy Estrogen Cohort 2 participants are in the longitudinal portion of the study and are TGWSM who are planning to initiate feminizing hormone therapy. Individuals in Cohort 2 will participate in study activities for 18 months. TGWSM Using Estrogen plus Progesterone Estrogen plus Progesterone Cohort 1 participants are in the cross-sectional study and will attend two study visits, participating in study activities for up to 12 weeks. Blood samples and rectal mucosal samples will be obtained. This group of participants in Cohort 1 consists of TGWSM currently using feminizing hormone therapy consisting of estrogen and progesterone. TGWSM Initiating Feminizing Hormone Therapy Estrogen plus Progesterone Cohort 2 participants are in the longitudinal portion of the study and are TGWSM who are planning to initiate feminizing hormone therapy. Individuals in Cohort 2 will participate in study activities for 18 months.
- Primary Outcome Measures
Name Time Method Change in Percent of Rectal Mucosal CD4+ T cells expressing CCR5 in Cohort 2 Baseline and up to 12 months after initiation of feminizing hormone therapy The median percentage of rectal mucosal CD4+ T cells that express CCR5 will be compared in Cohort 2, before hormone therapy begins and after hormone therapy.
Percent of Rectal Mucosal Cluster of Differentiation 4 (CD4+) T Cells Expressing C-C Chemokine Receptor Type 5 (CCR5) in Cohort 1 Day 1 (day of rectal mucosal sampling) The median percentage of rectal mucosal CD4+ T cells that express CCR5 will be compared between groups in Cohort 1.
Change in Production of p24 from Rectal Mucosal Explant Challenge in Cohort 2 Baseline and up to 12 months after initiation of feminizing hormone therapy The median production of p24 from rectal mucosal explant challenge experiments as measured by the area under the curve will be compared in Cohort 2, before hormone therapy begins and after hormone therapy.
Relative abundance of Prevotellaceae in Cohort 1 Day 1 (day of rectal mucosal sampling) The median relative abundance of Prevotellaceae measured from rectal mucosal secretions will be compared between groups in Cohort 1.
Change in Relative abundance of Prevotellaceae in Cohort 2 Baseline and up to 12 months after initiation of feminizing hormone therapy The median relative abundance of Prevotellaceae measured from rectal mucosal secretions will be compared in Cohort 2, before hormone therapy begins and after hormone therapy.
Production of p24 from Rectal Mucosal Explant Challenge in Cohort 1 Day 1 (day of rectal mucosal sampling) The median production of p24 from rectal mucosal explant challenge experiments as measured by the area under the curve will be compared between groups in Cohort 1.
Relative abundance of Bacteroidaceae in Cohort 1 Day 1 (day of rectal mucosal sampling) The median relative abundance of Bacteroidaceae measured from rectal mucosal secretions will be compared between groups in Cohort 1.
Change in Relative abundance of Bacteroidaceae in Cohort 2 Baseline and up to 12 months after initiation of feminizing hormone therapy The median relative abundance of Bacteroidaceae measured from rectal mucosal secretions will be compared in Cohort 2, before hormone therapy begins and after hormone therapy.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Hope Clinic
🇺🇸Atlanta, Georgia, United States