Drug Interaction
Conditions
Brief summary
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
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.
Interventions
DRUGEstradiol valerate 2 mg, cyproterone acetate 25 mg
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.
Sponsors
Thai Red Cross AIDS Research Centre
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Thai nationality 2. Age 18-40 years old 3. Transgender women 4. HIV-negative 5. Body mass index 18.5-24.9 kg/m2 6. Calculated creatinine clearance (CrCl) ≥60 mL/min, as estimated by the Cockcroft-Gault equation 7. Alanine aminotransferase (ALT) ≤2.5 x ULN 8. Signed the informed consent form
Exclusion criteria
1. Known history of allergy to hormonal component to be used in the study 2. Male-to-female transgender who underwent orchiectomy 3. Use of pre-exposure prophylaxis or post-exposure prophylaxis in the past 30 days 4. Use of injectable FHT in the past 3 months 5. Evidence of current hepatitis B virus infection (HBV) - i.e. hepatitis B surface antigen (HBsAg) positive 6. Evidence of current hepatitis C virus infection (HCV) - i.e. HCV antibody positive 7. 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 8. Participant-reported active rectal infection requiring treatment 9. History of gastrointestinal tract surgery that alter gastrointestinal tract and/or drug absorption 10. Alcohol or drug use that, in the opinion of the investigator, would interfere with completion of study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in plasma estradiol levels | Measured at week 3 and week 9 of the study period | — |
| Changes in plasma PrEP levels | Week 9 through 12 | 1. Plasma TFV 2. Plasma FTC 3. Plasma TAF |
| Changes in intracellular PrEP levels | Week 9 through 12 | 1. PBMC TFV-DP levels 2. PBMC FTC-TP levels |
Secondary
| Measure | Time frame |
|---|---|
| Changes in plasma testosterone levels | Week 3 through 9 |
Countries
Thailand
Outcome results
None listed