Drug Interaction
Conditions
Brief summary
There are currently no published studies addressing drug-drug interactions (DDI) between masculinizing hormone therapy (MHT) and pre-exposure prophylaxis (PrEP) among transgender men (TGM). This could lead to concerns and subsequent prioritizing MHT over PrEP among TGM. Because tenofovir alafenamide (TAF) can achieve higher intracellular tenofovir diphosphate (TFV-DP) levels with lower tenofovir plasma concentrations, it is promising that both plasma tenofovir (TFV) and intracellular TFV-DP levels might not be significantly affected by MHT. The current study aims to determine the pharmacokinetics (PK) DDI between MHT and daily PrEP among TGM.
Interventions
DRUGEmtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF)
The first full PK measurement of MHT will be performed starting at week 4 and end at week 6 to assess the steady-state plasma PK of testosterone in the absence of PrEP. The second PK measurement of MHT will be performed starting at week 12 and end at week 14 to assess plasma PK of testosterone in the presence of both MHT and PrEP. The first full PK measurement of PrEP will be performed at week 12 to assess the steady-state plasma PK of FTC, TFV, and TAF; and intracellular PBMC FTC-TP and TFV-DP in the presence of both MHT and PrEP. The second measurement of PrEP will be performed at week 16 to assess plasma PK of FTC, TFV, and TAF; and intracellular PBMC FTC-TP and TFV-DP in the absence of MHT.
Sponsors
Thai Red Cross AIDS Research Centre
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
An open-label, randomized, two-arm prospective PK study of HIV-negative TGM taking MHT and daily PrEP: Arm 1: Twenty HIV-negative TGM will take daily TDF/FTC-based PrEP Arm 2: Twenty HIV-negative TGM will take daily F/TAF-based PrEP
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Thai nationality 2. Age 18-40 years old 3. Female-to-Male transgender individual 4. HIV-negative 5. Body mass index 18.5-24.9 kg/m2 6. Negative urine pregnancy test 7. Calculated creatinine clearance (CrCl) ≥60 mL/min, as estimated by the Cockcroft-Gault equation 8. Alanine aminotransferase (ALT) ≤2.5 x ULN 9. Signed the informed consent form
Exclusion criteria
1. Known history of allergy to hormonal component to be used in the study 2. Use of pre-exposure prophylaxis or post-exposure prophylaxis in the past 30 days 3. Use of injectable MHT in the past 3 months 4. Evidence of current hepatitis B virus infection (HBV) - i.e. hepatitis B surface antigen \[HBsAg\] positive 5. Evidence of current hepatitis C virus infection (HCV) - i.e. HCV antibody positive 6. History of myocardial infarction or coronary artery disease 7. Current use of any of the following: * Anticonvulsants: carbamazepine, oxcarbazepine, phenytoin, or phenobarbital * Herbs: gingko biloba, St John's wort or milk thistle * Anti-infective agents: protease inhibitors, rifampicin or rifabutin 8. History of gastrointestinal tract surgery that alter gastrointestinal tract and/or drug absorption 9. 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 TFV level | 2 years | 1. Changes in plasma testosterone levels \[Time Frame: Measured at week 4 and week 12 of the study period\] 2. Changes in plasma TFV levels \[Time Frame: Measured at week 12 and week 16 of the study period\] 3. Changes in plasma emtricitabine (FTC) levels \[Time Frame: Measured at week 12 and week 16 of the study period\] 4. Changes in plasma TAF levels \[Time Frame: Measured at week 12 and week 16 of the study period\] 5. Changes in peripheral blood mononuclear cell TFV-DP levels \[Time Frame: Measured at week 12 and week 16 of the study period\] 6. Changes in peripheral blood mononuclear cell (PBMC) emtricitabine triphosphate (FTC-TP) levels \[Time Frame: Measured at week 12 and week 16 of the study period\] |
Countries
Thailand
Outcome results
None listed