This study explores how feminizing hormone therapy affects the immune system in the rectal area of transgender women. Transgender women are individuals who were assigned male at birth but identify as female and may take hormones to affirm their gender. The study aims to improve HIV prevention techniques, as the rectal area can be a site for HIV infection. There are two groups in the study: one involves transgender women already on hormone therapy, and the other involves those planning to start hormone therapy. A total of 520 participants are expected, including cisgender men (men assigned male at birth and who identify as male) for comparison.

• Participation Length: Cohort 1 requires up to 12 weeks, and Cohort 2 requires 18 months.
• Activities: Participants will undergo blood and rectal tests and must avoid anal intercourse around testing times.
• Eligibility: Participants must be HIV-negative, able to give consent, and meet specific hormone use criteria.