40 Impact of feminizing hormone therapy on rectal mucosal HIV target cells in Thai TGWSM

Objectives/Goals: Transgender women who have sex with men (TGWSM) have higher HIV risk. The rectal mucosal (RM) immune environment of TGWSM who choose feminizing hormone therapy (FHT) has been shown to be distinct from the RM of cisgender men who have sex with men (MSM). We studied the impact of FHT on the adaptive immune cellular composition of the RM. Methods/Study Population: We sampled cross-sectional and longitudinal cohorts of TGWSM and cisgender MSM from The Silom Clinic in Bangkok, Thailand from December 2020 to December 2023. We included participants aged >18 years, all cisgender MSM and TGWSM with FHT levels in the therapeutic range for cisgender women. We performed RM biopsies and analyzed the adaptive immune cell characteristics via flow cytometry. We will perform binary linear regression to assess the association between systemic FHT levels and the percentage of CD4+ T cells expressing key biomarkers. Primary outcomes include the percentage of CD4+ T cells that express CCR5, with a secondary outcome of the percentage of CD4+ T cells that express Ki67. Results/Anticipated Results: The cross-sectional cohort included 100 TGWSM on FHT and 50 cisgender MSM. The longitudinal cohort included 25 TGWSM who were initiating FHT. Similar primary and secondary outcomes are to be elucidated in both cohorts. We anticipate the RM environment of TGWSM using FHT in both cohorts compared to the RM environment of cisgender MSM in the cross-sectional cohort will be associated with greater percentages of activation/co-receptor expression of CD4+ T cells that express biomarkers of interest. In the longitudinal cohort, we similarly anticipate increased percentages and activation/co-receptor expression of CD4+ T cells expressing biomarkers of interest in TGWSM after in comparison to before initiating FHT. Discussion/Significance of Impact: This is the largest study of its kind to compare HIV target cells in RM of TGSWM, which challenges prevailing perspectives suggesting to group cisgender MSM with TGWSM. Anticipated results will inform HIV prevention strategies and future vaccine studies in this high-risk population.