Clinical trial NCT04590417: Assessment of Drug-drug Interactions Between Feminizing Hormone Therapy and Emtricitabine/Tenofovir Alafenamide Concomitantly for Pre-exposure Prophylaxis Among Transgender Women
Official title: Institute of HIV Research and Innovation (IHRI)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Drug Interaction
Lead sponsor: Thai Red Cross AIDS Research Centre
Sponsor class: OTHER
First posted: 2020-10-19
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in plasma estradiol levels
timeFrame: Measured at week 3 and week 9 of the study period
measure: Changes in plasma PrEP levels
timeFrame: Week 9 through 12
measure: Changes in intracellular PrEP levels
timeFrame: Week 9 through 12
Secondary outcomes:
measure: Changes in plasma testosterone levels
timeFrame: Week 3 through 9
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Institute of HIV Research and Innovation (IHRI)
state: Pathumwan
Study officials:
affiliation: Institute of HIV Research and Innovation (IHRI)
name: Siriporn Nonenoy, RN.MPH.
role: STUDY_CHAIR
References: