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

Institute of HIV Research and Innovation (IHRI)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Drug Interaction
• Intervention / Treatment: Drug: Estradiol valerate 2 mg, cyproterone acetate 25 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Pathumwan
    • Bangkok, Pathumwan, Thailand, 10330
      • Institute of HIV Research and Innovation (IHRI)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 20 HIV-negative TGW; A single-arm prospective PK study of HIV-negative TGW taking FHT and daily PrEP.	Drug: Estradiol valerate 2 mg, cyproterone acetate 25 mg; The entire study period will be approximately 1 year, which will include around 2 months of document preparation, 5 months of recruitment, 3 months of follow-up, and 2 months of data analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in plasma estradiol levels		Measured at week 3 and week 9 of the study period
Changes in plasma PrEP levels	Plasma TFV; Plasma FTC; Plasma TAF	Week 9 through 12
Changes in intracellular PrEP levels	PBMC TFV-DP levels; PBMC FTC-TP levels	Week 9 through 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in plasma testosterone levels	Week 3 through 9

Collaborators and Investigators

• Sponsor: Thai Red Cross AIDS Research Centre
• Investigators: Study Chair: Siriporn Nonenoy, RN.MPH., Institute of HIV Research and Innovation (IHRI)

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: October 7, 2020
• First Submitted That Met QC Criteria: October 14, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Androgen Antagonists; Contraceptive Agents, Male; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Cyproterone Acetate; Cyproterone
• Other Study ID Numbers: iFACT 3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No