Assessment of Drug-drug Interactions Between Masculinizing Hormone Therapy and Antiretroviral Agents Concomitantly for Pre-exposure Prophylaxis Among Transgender Men

Not Applicable

Active, not recruiting

• Conditions: Drug Interaction
• Interventions: Drug: Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF)

• Registration Number: NCT04593680
• Lead Sponsor: Thai Red Cross AIDS Research Centre

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-10-14
• Study First Submitted QC: 2020-10-19
• Study First Posted: 2020-10-20
• Study Start: 2022-01-24
• Primary Completion: 2023-10-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-22
• Last Update Posted: 2024-11-25
• Study Completion: 2025-10-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
20 HIV-negative TGM will take daily TDF/FTC-based PrEP	Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF)	MHT will be initiated on week 0 and will be last administered on week 12. PrEP will be initiated on week 6 and continued without interruption. MHT: Intramuscular testosterone enanthate 200 mg bi-weekly, which is the treatment of choice for MHT in the Pribta Clinic, will be provided to all participants. PrEP: Fixed-dose combination of emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF) will be provided for arm 1 and 2, respectively. Pharmacokinetic measurement of study drug Two full pharmacokinetic (PK) measurements will be performed. Samples collected will include: plasma for testosterone, emtricitabine (FTC) and tenofovir (TFV), with an additional tenofovir alafenamide (TAF).
20 HIV-negative TGM will take daily F/TAF-based PrEP	Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF)	MHT will be initiated on week 0 and will be last administered on week 12. PrEP will be initiated on week 6 and continued without interruption. MHT: Intramuscular testosterone enanthate 200 mg bi-weekly, which is the treatment of choice for MHT in the Pribta Clinic, will be provided to all participants. PrEP: Fixed-dose combination of emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF) will be provided for arm 1 and 2, respectively. Pharmacokinetic measurement of study drug Two full pharmacokinetic (PK) measurements will be performed. Samples collected will include: arm 2, measurement; and peripheral blood mononuclear cells (PBMC) for emtricitabine-triphosphate (FTC-TP) and tenofovir-diphosphate (TFV-DP) intracellular quantification.

Primary Outcome Measures

Name	Time	Method
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 \[Time Frame: Measured at week 12 and week 16 of the study period\]

Trial Locations

Locations (1)

Institute of HIV Research and Innovation (IHRI); 🇹🇭 Bangkok, Pathumwan, Thailand