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

Thai Red Cross AIDS Research Centre

Status: Active, not recruiting

Conditions: Drug Interaction

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

Study type: Interventional

Funder types: Other

Identifiers

NCT04593680

iMACT

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

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

Experimental group

Description:

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).

Treatment:

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

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

Experimental group

Description:

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.

Treatment:

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