The purpose of this study is to see if human immunodeficiency virus (HIV) antiretroviral therapy (ART) medicines continue to work well in transgender women (TW) and other individuals identifying as female or transfeminine but with male sex assigned at birth when taken with feminizing hormone therapy (FHT), also known in this study as estradiol. The study will determine if TW remain undetectable while receiving FHT for 48 weeks. Additionally, it will assess if hormone levels change based on the type of HIV medication taken. 

The study drug in this trial is estradiol. Estradiol is used for gender-affirming therapy by TW. Its use in this study is considered investigational, which means it is not approved by the U.S. Food and Drug Administration (FDA) for gender-affirming therapy for transgender women. It is FDA approved for other uses. 

This study has three groups and is not randomized. This means that all three groups will receive the study drug estradiol. 

Participants will also have physical exams, provide blood samples, and complete questionnaires regarding goals for estradiol use, nicotine use, and mental health.