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Assessment of Drug-drug Interactions Between Feminizing Hormone Therapy and Emtricitabine/Tenofovir Alafenamide Concomitantly for Pre-exposure Prophylaxis Among Transgender Women

Not Applicable
Active, not recruiting
Conditions
Drug Interaction
Interventions
Registration Number
NCT04590417
Lead Sponsor
Thai Red Cross AIDS Research Centre
Brief Summary

Recent studies have showed that there were significant drug-drug interactions (DDI) from feminizing hormone therapy (FHT) towards emtricitabine/tenofovir disoproxil fumarate (F/TDF)-based pre-exposure prophylaxis (PrEP) among transgender women (TGW). New strategies for PrEP among TGW who use FHT are urgently needed. Because tenofovir alafenamide (TAF) can achieve higher intracellular TFV-DP levels with lower tenofovir plasma concentrations, it is promising that both plasma TFV and intracellular TFV-DP levels might not be significantly affected by FHT. The current study aims to determine the pharmacokinetics DDI between FHT and F/TAF-based PrEP among TGW.

Detailed Description

Two full pharmacokinetic (PK) measurements will be performed. Samples collected will include: plasma for estradiol (E2), emtricitabine (FTC), tenofovir (TFV), and tenofovir alafenamide (TAF) measurement; and peripheral blood mononuclear cells (PBMC) for emtricitabine-triphosphate (FTC-TP) and tenofovir-diphosphate (TFV-DP) intracellular quantification.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
20
Inclusion Criteria
  1. Thai nationality
  2. Age 18-40 years old
  3. Transgender women
  4. HIV-negative
  5. Body mass index 18.5-24.9 kg/m2
  6. Calculated creatinine clearance (CrCl) ≥60 mL/min, as estimated by the Cockcroft-Gault equation
  7. Alanine aminotransferase (ALT) ≤2.5 x ULN
  8. Signed the informed consent form
Exclusion Criteria
  1. Known history of allergy to hormonal component to be used in the study

  2. Male-to-female transgender who underwent orchiectomy

  3. Use of pre-exposure prophylaxis or post-exposure prophylaxis in the past 30 days

  4. Use of injectable FHT in the past 3 months

  5. Evidence of current hepatitis B virus infection (HBV) - i.e. hepatitis B surface antigen (HBsAg) positive

  6. Evidence of current hepatitis C virus infection (HCV) - i.e. HCV antibody positive

  7. Current use of any of the following:

    • Anticonvulsants: carbamazepine, felbamate, oxcarbazepine, phenytoin, phenobarbital, primidone or topiramate
    • Herbs: gingko biloba, St John's wort or milk thistle
    • Anti-infective agents: azole antifungals, macrolides, griseofulvin, protease inhibitors, rifampicin or rifabutin
  8. Participant-reported active rectal infection requiring treatment

  9. History of gastrointestinal tract surgery that alter gastrointestinal tract and/or drug absorption

  10. 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
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
20 HIV-negative TGWEstradiol valerate 2 mg, cyproterone acetate 25 mgA single-arm prospective PK study of HIV-negative TGW taking FHT and daily PrEP.
Primary Outcome Measures
NameTimeMethod
Changes in plasma estradiol levelsMeasured at week 3 and week 9 of the study period
Changes in plasma PrEP levelsWeek 9 through 12

1. Plasma TFV

2. Plasma FTC

3. Plasma TAF

Changes in intracellular PrEP levelsWeek 9 through 12

1. PBMC TFV-DP levels

2. PBMC FTC-TP levels

Secondary Outcome Measures
NameTimeMethod
Changes in plasma testosterone levelsWeek 3 through 9

Trial Locations

Locations (1)

Institute of HIV Research and Innovation (IHRI)

🇹🇭

Bangkok, Pathumwan, Thailand

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