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

Study Overview
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Brief Summary
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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.

Official Title
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Institute of HIV Research and Innovation (IHRI)

Conditions
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Drug Interaction

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Thai nationality Age 18-40 years old Female-to-Male transgender individual HIV-negative Body mass index 18.5-24.9 kg/m2 Negative urine pregnancy test Calculated creatinine clearance (CrCl) ≥60 mL/min, as estimated by the Cockcroft-Gault equation Alanine aminotransferase (ALT) ≤2.5 x ULN Signed the informed consent form Exclusion Criteria: Known history of allergy to hormonal component to be used in the study Use of pre-exposure prophylaxis or post-exposure prophylaxis in the past 30 days Use of injectable MHT in the past 3 months Evidence of current hepatitis B virus infection (HBV) - i.e. hepatitis B surface antigen [HBsAg] positive Evidence of current hepatitis C virus infection (HCV) - i.e. HCV antibody positive History of myocardial infarction or coronary artery disease 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 History of gastrointestinal tract surgery that alter gastrointestinal tract and/or drug absorption Alcohol or drug use that, in the opinion of the investigator, would interfere with completion of study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20 HIV-negative TGM will take daily TDF/FTC-based PrEP<br>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). | Drug: Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF)<br>* 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.<br>|
| Experimental: 20 HIV-negative TGM will take daily F/TAF-based PrEP<br>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. | Drug: Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma TFV level | Changes in plasma testosterone levels [Time Frame: Measured at week 4 and week 12 of the study period] Changes in plasma TFV levels [Time Frame: Measured at week 12 and week 16 of the study period] Changes in plasma emtricitabine (FTC) levels [Time Frame: Measured at week 12 and week 16 of the study period] Changes in plasma TAF levels [Time Frame: Measured at week 12 and week 16 of the study period] Changes in peripheral blood mononuclear cell TFV-DP levels [Time Frame: Measured at week 12 and week 16 of the study period] 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] | 2 years |