The GET IT RIgHT Study

Phase 2

• Conditions: B20 Human immunodeficiency virus [HIV] disease resulting in infectious and parasitic diseases; Human immunodeficiency virus [HIV] disease resulting in infectious and parasitic diseases

• Registration Number: PER-033-23
• Lead Sponsor: Instituto Nacional de Alergias y Enfermedades Infecciosas NIAID

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-06-19
• Last Update Posted: 20 August 2024

Recruitment & Eligibility

• Status: Without startig enrollment
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

Age =18 years.

HIV-1, documented by any licensed rapid HIV test ar HIV enzyme ar chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot ar a second antibody test by a method other than the initial rapid HIV and/or E/CIA, ar by HIV-1 antigen, plasma HIV-1 RNA viral load.

Assigned male sex at birth and identifies as a transwomen, female or transfeminine person (referred in aggregate as TW).

On antiretroviral therapy (ART) for at least 24 weeks prior to study entry. Regimen changes within the 24 weeks prior to study entry are acceptable, but candidates must have been on a stable regimen for at least 28 days prior to study entry.

On bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), dolutegravir/tenofovir disoproxil fumarate/FTC or lamivudine (DTG/TDF/FTC or 3TC), or darunavir/cobicistat (DRV/c)-containing ART for at least 28 days prior to study entry (single tablet regimen not required), and with no plans to change ART regimen over the study duration of 48 weeks.

Desire to initiate or restart feminizing hormone therapy (FHT), regardless of orchiectomy status.

HIV-1 RNA <200 copies/ml ( ar below the assay limit of detection if local assay lower limit of detection is >200 copies/ml) at screening (within 60 days prior to entry).

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

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 or switching to TAF, ar =50 ml/min/1.73m2 if on or switching to TDF without cobicistat, or =70 mL/min/1.73m2 if on or switching to TDF in combination with cobicistat, 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

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

Willingness to avoid the use of prescribed,

Exclusion Criteria

Known or a history of testicular cancer.

Known or a history of gall bladder disease.

Known or suspected pituitary adenoma.

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

Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

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

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

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

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

Known liver impairment or disease.

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

History of current active hepatitis C virus infection.

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

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

Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry. Stable (in the opinion of the site investigator) treatments for chronic comorbidities are allowed.

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
a. Intra-person geometric ratio of the concentration of BIC, DTG and DRV.<br>b. Indicator of concentration of BIC, DTG and DRV.<br> NAME OF THE RESULT: Trough concentration of the analytes BIC, DTG, and DRV in plasma at each received dose of oral 17-ß estradiol (0 (pre-FHT or baseline), 2, 4, 6, 8, 10 mg).<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: 0, 4, 12, 24, 36 y 48 weeks. ;Estradiol serum concentration.<br> NAME OF THE RESULT: Trough serum total estradiol assessed at each received dose of oral 17-ß estradiol (i.e., 2 mg, 4 mg, 6 mg, 8 mg, 10 mg).<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: 0, 4, 12, 24, 36 y 48 weeks.