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

NCT ID: NCT04593680

Last Updated: 2024-11-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-24
• Study Completion Date: 2025-10-01

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.

Conditions

Drug Interaction

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

20 HIV-negative TGM will take daily TDF/FTC-based PrEP

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).

Group Type: EXPERIMENTAL

Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF)

Intervention Type: DRUG

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.

20 HIV-negative TGM will take daily F/TAF-based PrEP

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.

Group Type: EXPERIMENTAL

Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF)

Intervention Type: DRUG

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.

Interventions

Emtricitabine 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Thai Red Cross AIDS Research Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institute of HIV Research and Innovation (IHRI)

Bangkok, Pathumwan, Thailand

Countries

Thailand

References

Hiransuthikul A, Thammajaruk N, Kerr S, Janamnuaysook R, Nonenoy S, Hongchookiat P, Trichavaroj R, Tawon Y, Boonruang J, Teeratakulpisarn N, Cressey TR, Anderson PL, Phanuphak N; iMACT study team. Exploring potential drug-drug interactions between masculinizing hormone therapy and oral pre-exposure prophylaxis (F/TDF and F/TAF) among transgender men (iMACT study): a randomized, open-label pharmacokinetic study in Thailand. J Int AIDS Soc. 2025 Apr;28(4):e26445. doi: 10.1002/jia2.26445.

Reference Type: DERIVED

PMID: 40195242 (View on PubMed)

Other Identifiers

iMACT

Identifier Type: -

Identifier Source: org_study_id