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

Sponsor

Thai Red Cross AIDS Research Centre (Other)

Overall Status

Recruiting

CT.gov ID

NCT04590417

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Drug Interaction	Drug: Estradiol valerate 2 mg, cyproterone acetate 25 mg	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Institute of HIV Research and Innovation (IHRI)

Actual Study Start Date :

Oct 1, 2020

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Changes in plasma estradiol levels [Measured at week 3 and week 9 of the study period]
Changes in plasma PrEP levels [Week 9 through 12]
Plasma TFV Plasma FTC Plasma TAF
Changes in intracellular PrEP levels [Week 9 through 12]
PBMC TFV-DP levels PBMC FTC-TP levels

Secondary Outcome Measures

Changes in plasma testosterone levels [Week 3 through 9]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Thai nationality
Age 18-40 years old
Transgender women
HIV-negative
Body mass index 18.5-24.9 kg/m2
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
Male-to-female transgender who underwent orchiectomy
Use of pre-exposure prophylaxis or post-exposure prophylaxis in the past 30 days
Use of injectable FHT 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
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

Participant-reported active rectal infection requiring treatment
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