Inclusion Criteria:

• 1. 18 years of age or older
• 2. Self-identifying as a transgender woman
• 3. Not currently taking any gender affirming hormonal therapy (GAHT) with a total testosterone concentration of ≥ 200 ng/dL, or willing to abstain from feminizing therapies (including estradiol, spironolactone, progesterone, etc.) until total total testosterone concentrations are ≥ 200 ng/dL. Note: Testosterone may be retested every 2-4 weeks during screening to determine eligibility up to 6 weeks.
• 4. HIV-1 uninfected at screening as documented by Combo Ag/Ab HIV-1/HIV-2 immunoassay
• 5. Understand and agree to local STI reporting requirements
• 6. Able and willing to communicate in English
• 7. Able and willing to provide written informed consent to take part in the study
• 8. Able and willing to provide adequate information for locator purposes
• 9. Able and willing to participate in a directly observed study, which may occur in person, using live streaming or a time stamped video?
• 10. Availability to return for all study visits, barring unforeseen circumstances
• 11. Willing to abstain from insertion of anything (drug, enema, penis, or sex toy) in rectum for 72 hours before and 72 hours after each flexible sigmoidoscopy
• 12. Willing to refrain from aspirin and NSAID use for one week before and after each study biopsy visit
• 13. Willing and able to use condoms for all Receptive Anal Intercourse (RAI) for the duration of participation
• 14. Willing and able to participate in a directly observed study, which may occur in person, using live streaming or a time stamped video
• 15. Has an identified healthcare provider for transgender health management
• 16. Agree not to participate in other research studies involving drugs and/or medical devices for the duration of the study

Exclusion Criteria:

• 1. Not currently on any PrEP regimen (e.g., Truvada®, tenofovir alafenamide/ emtricitabine)
• 2. History of chronic Hepatitis B infection, as documented by positive HBsAg at screening
• 3. ≥ Grade 2 laboratory abnormality at baseline as defined by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 - July 2017, and Addendum 3 (Rectal Grading Tables for Use in Microbicide Studies)
• 4. Significant colorectal symptom(s) as determined by medical history or by participant self- report (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, history of inflammatory bowel disease, presence of symptomatic hemorrhoids, and presence of any painful anorectal conditions that would be tender to manipulation)
• 5. At screening or within the past 2 months: participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal infection requiring treatment per current Centers for Disease Control (CDC) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include Chlamydia (CT), gonorrhea (GC), syphilis, active herpes simplex virus (HSV) lesions, chancroid, genital sores or ulcers, and, if clinically indicated, genital warts. Note that HSV seropositivity with no active genital lesions is not an exclusion criterion. (Note: if an Sexually Transmitted Infection (STI) apart from HIV is detected, the participant will be referred for treatment and can be retested in 30 days and rescreened once.)
• 6. History of an underlying clinically significant cardiac arrhythmia or renal disease (including creatinine clearance \< 60 mL/min using Cockcroft-Gault equation)
• 7. Serum phosphate \< 2.3 mg/dL
• 8. History of severe or recent cardiac or pulmonary event
• 9. History of significant gastrointestinal bleeding
• 10. Current use of warfarin or heparin or other anticoagulant medications associated with increased risk for bleeding following mucosal biopsy (e.g., daily high dose aspirin \[\>81 mg\], Non-steroidal anti-inflammatory drug \[NSAIDs\], or Pradaxa®)
• 11. Use of systemic or anorectal immunomodulatory medications within 4 weeks of enrollment or planned use at any time during study participation