Assessment of Drug-drug Interactions Between Feminizing Hormone Therapy and Emtricitabine/Tenofovir Alafenamide Concomitantly for Pre-exposure Prophylaxis Among Transgender Women

Study Overview
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Brief Summary
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Recent studies have showed that there were significant drug-drug interactions (DDI) from feminizing hormone therapy (FHT) towards emtricitabine/tenofovir disoproxil fumarate (F/TDF)-based pre-exposure prophylaxis (PrEP) among transgender women (TGW). New strategies for PrEP among TGW who use FHT are urgently needed. Because tenofovir alafenamide (TAF) can achieve higher intracellular TFV-DP levels with lower tenofovir plasma concentrations, it is promising that both plasma TFV and intracellular TFV-DP levels might not be significantly affected by FHT. The current study aims to determine the pharmacokinetics DDI between FHT and F/TAF-based PrEP among TGW.

Detailed Description
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Two full pharmacokinetic (PK) measurements will be performed. Samples collected will include: plasma for estradiol (E2), emtricitabine (FTC), tenofovir (TFV), and tenofovir alafenamide (TAF) measurement; and peripheral blood mononuclear cells (PBMC) for emtricitabine-triphosphate (FTC-TP) and tenofovir-diphosphate (TFV-DP) intracellular quantification.

Official Title
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Institute of HIV Research and Innovation (IHRI)

Conditions
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Drug Interaction

Intervention / Treatment
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* Drug: Estradiol valerate 2 mg, cyproterone acetate 25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Thai nationality Age 18-40 years old Transgender women HIV-negative Body mass index 18.5-24.9 kg/m2 Calculated creatinine clearance (CrCl) ≥60 mL/min, as estimated by the Cockcroft-Gault equation Alanine aminotransferase (ALT) ≤2.5 x ULN Signed the informed consent form Exclusion Criteria: Known history of allergy to hormonal component to be used in the study Male-to-female transgender who underwent orchiectomy Use of pre-exposure prophylaxis or post-exposure prophylaxis in the past 30 days Use of injectable FHT in the past 3 months Evidence of current hepatitis B virus infection (HBV) - i.e. hepatitis B surface antigen (HBsAg) positive Evidence of current hepatitis C virus infection (HCV) - i.e. HCV antibody positive Current use of any of the following: Anticonvulsants: carbamazepine, felbamate, oxcarbazepine, phenytoin, phenobarbital, primidone or topiramate Herbs: gingko biloba, St John's wort or milk thistle Anti-infective agents: azole antifungals, macrolides, griseofulvin, protease inhibitors, rifampicin or rifabutin Participant-reported active rectal infection requiring treatment History of gastrointestinal tract surgery that alter gastrointestinal tract and/or drug absorption Alcohol or drug use that, in the opinion of the investigator, would interfere with completion of study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 20 HIV-negative TGW<br>A single-arm prospective PK study of HIV-negative TGW taking FHT and daily PrEP. | Drug: Estradiol valerate 2 mg, cyproterone acetate 25 mg<br>* The entire study period will be approximately 1 year, which will include around 2 months of document preparation, 5 months of recruitment, 3 months of follow-up, and 2 months of data analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma estradiol levels |  | Measured at week 3 and week 9 of the study period | 
| Changes in plasma PrEP levels | Plasma TFV Plasma FTC Plasma TAF | Week 9 through 12 | 
| Changes in intracellular PrEP levels | PBMC TFV-DP levels PBMC FTC-TP levels | Week 9 through 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma testosterone levels |  | Week 3 through 9 |