Finding the Right Tenofovir/Emtricitabine Regimen for Pre-Exposure Prophylaxis (PrEP) in Transgender Women

This is an open-label, steady-state study of Tenofovir (TFV) and Emtricitabine (FTC) pharmacokinetics (PK) in transgender women taking feminizing hormones. Half of the participants will be transgender women on feminizing hormones, the other half will be male volunteers not taking any hormone therapy.

Study Overview

• Status: Completed
• Conditions: HIV Prevention
• Intervention / Treatment: Drug: Tenofovir Disoproxil Fumarate/Emtricitabine

Detailed Description

The investigators propose an open-label, steady-state study of TFV and FTC PK in blood and colon tissue in healthy TGW on feminizing hormones to be compared to healthy cis men, all at risk for HIV infection. Research participants will already have received eight days of TDF/FTC dosing. Evaluating TDF and FTC PK at steady-state is important as it reduces inter-individual variability since the rate of phosphorylation of TFV and FTC is highly variable, resulting in highly variable TFV-DP and Emtricitabine-Triphosphate (FTC-TP) PK among individuals in the first day and during rise to steady-state.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University Drug Development Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• TGW and cis men (male at birth and not a TGW)
• 18 to 65 years of age, inclusive on the date of screening
• Provides informed consent for the study
• Non-reactive HIV test results within four weeks of enrollment
• An estimated calculated creatinine clearance (eCcr) of at least 70 mL/min
• Agrees to use condoms for all sexual events during study participation.
• Taking daily oral Truvada® (Tenofovir disoproxil fumarate (TDF) 300 mg/Emtricitabine (FTC) 200 mg) for at least one week at the time of study PK sampling visit
• TGW have to be on an estradiol and have a serum total estradiol level > 100 picograms(pg)/ml

Exclusion Criteria:

• Significant colorectal symptom(s) as determined by medical history or by participant self-report
• Participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal infection requiring treatment per current Centers for Disease Control (CDC) guidelines
• A positive test for Herpes Simplex Virus -2 (HSV-2) (individuals with active lesions only)
• Co-enrollment in any other HIV interventional research study (excluding behavioral only interventions) or prior enrollment in the active arm of a HIV vaccine trial.
• Positive hepatitis B surface antigen (HBsAg) test
• Interleukin therapy; medications with significant nephrotoxic potential, including but not limited to amphotericin B, aminoglycosides, cidofovir, foscarnet and systemic chemotherapy; medications that may inhibit or compete for elimination via active renal tubular secretion (including but not limited to probenecid); systemic immunomodulatory medications
• Participants with a history of having a gastrectomy, colostomy, ileostomy, or any other procedure altering the gastrointestinal tract or drug absorption
• Medications that prolong clotting time
• Any other condition or prior therapy that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, make the individual unsuitable for the study or unable to comply with the study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TFV/FTC dosing in Transgender women; Single daily dose of oral Tenofovir Disoproxil Fumarate/Emtricitabine (Truvada)for 7days in transgender women taking feminizing hormones	Drug: Tenofovir Disoproxil Fumarate/Emtricitabine; Other Names: Truvada
Active Comparator: TFV/FTC dosing in Cis men; Single daily dose of oral Tenofovir Disoproxil Fumarate/Emtricitabine (Truvada) for 7days in cis men	Drug: Tenofovir Disoproxil Fumarate/Emtricitabine; Other Names: Truvada

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colon tissue tenofovir diphosphate (TFV-DP)	Endoscopy will be performed to obtain colorectal tissue biopsies. 15 biopsies will be collected and processed to isolate mucosal mononuclear cells (MMC). TFV-DP will be measured and reported as femtomoles per million cells (fmole/10E6 cells).	One week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ex vivo colon explant HIV challenge	Colorectal tissue biopsies will be collected and exposed ex vivo to HIV and kept in culture for 15 days. Every three days a sample of fluid bathing the tissue sample will be tested for HIV p24 antigen. Results will be reported as picograms of p24 per milliliter (pg/mL).	One week

Collaborators and Investigators

• Sponsor: Johns Hopkins University

Publications and helpful links

General Publications

• Shieh E, Marzinke MA, Fuchs EJ, Hamlin A, Bakshi R, Aung W, Breakey J, Poteat T, Brown T, Bumpus NN, Hendrix CW. Transgender women on oral HIV pre-exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men. J Int AIDS Soc. 2019 Nov;22(11):e25405. doi: 10.1002/jia2.25405.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2016
• Primary Completion (Actual): May 31, 2018
• Study Completion (Actual): May 31, 2018

Study Registration Dates

• First Submitted: February 17, 2017
• First Submitted That Met QC Criteria: February 17, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine
• Other Study ID Numbers: IRB00092121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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