Estradiol Therapy In Transgender Women to Research Interactions With HIV Therapy

Inclusion Criteria:

1. Age greater than or equal to 18 years.

2. Documentation of HIV-1 status.

3. Assigned male sex at birth and identifies as a TW, female or transfeminine person.

4. On ART for at least 24 weeks prior to study entry. Regimen changes within the 24weeks prior to study entry are acceptable, but candidates must have been on a stableregimen for at least 28 days prior to study entry.

5. On BIC/FTC/TAF, DTG/TDF/FTC or 3TC, or DRV/c-containing ART for at least 28 daysprior to study entry (single tablet regimen not required), and with no plans tochange ART regimen over the study duration of 48 weeks.

6. Desire to initiate or restart FHT, regardless of orchiectomy status.

7. HIV-1 RNA <200 copies/mL at screening.

8. HIV-1 RNA <400 copies/mL available through routine clinical care between 24 and 96weeks prior to study entry and while on ART. The HIV-1 RNA must be the most recentvalue obtained between 24 and 96 weeks prior to study entry.

9. The following laboratory values obtained within 60 days prior to study entry

• Hemoglobin ≥9.0 g/dL

• Platelet count ≥75,000/mm3

• Estimated Glomerular Filtration Rate (eGFR) ≥30 mL/min/1.73m2 if on orswitching to TAF, ≥50 mL/min/1.73m2 if on or switching to TDF withoutcobicistat, or ≥70 mL/min/1.73m2 if on or switching to TDF in combination withcobicistat, calculated using the CKD-Epi equation

• Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT),and alkaline phosphatase are within normal range per local laboratory range

• Prolactin <25 ng/dL

10. Serum estradiol level <75 pg/mL within 60 days prior to study entry.

11. Willingness to avoid the use of prescribed, non-study provided FHT andnon-prescribed FHT during the study period, and no planned use of prescribed ornon-prescribed anti-androgens for the first 24 weeks of the study.

12. Ability and willingness of participant to provide informed consent and ability andwillingness of participant to undergo study procedures.

Exclusion Criteria:

1. Known clotting disorders, active deep vein thrombosis (DVT), pulmonary embolism (PE), or history of these conditions, active arterial thromboembolic disease (e.g.,stroke, myocardial infarction), or history of these conditions.

2. Known liver impairment or disease.

3. History of chronic hepatitis B virus (HBV) infection or active HBV infection.

4. History of current active hepatitis C virus (HCV) infection.

5. Prohibited medication use (including drugs with known or expected DDIs with FHT orART) at time of study entry.

6. Receipt of any estrogen therapy within 14 days prior to study entry for persons onoral FHT, or within 30 days prior to entry for persons on injectable FHT.

7. Known HIV-1 resistance mutations that would preclude remaining on current ART or aswitch to a study regimen, in the opinion of the site investigator.

8. Personal history of breast cancer. or known personal history of breast cancer (BRCA)gene.

9. Known or a history of testicular cancer.

10. Known or a history of gall bladder disease.

11. Known or suspected pituitary adenoma.

12. Known allergy/sensitivity or any hypersensitivity to components of study drugs ortheir formulation.

13. Known allergy/sensitivity or any hypersensitivity to components of study drugs ortheir formulation.

14. Suicidal ideation in the past 30 days or suicide attempt in the past 90 days, asreported on the Columbia-Suicide Severity Rating Scale (C-SSRS).

15. Serious illness requiring systemic treatment and/or hospitalization within 30 daysprior to entry. Stable (in the opinion of the site investigator) treatments forchronic comorbidities are allowed.

16. Presence of any other medical condition that would preclude FHT administration forsafety reasons, in the opinion of the site investigator.