A Pharmacokinetic Evaluation of Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis in Transgender Women

Pharmacokinetics of Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Pre-exposure Prophylaxis in Transgender Women Receiving Feminizing Hormone Therapy

Human immunodeficiency virus (HIV) persists worldwide as an immense health burden among vulnerable populations. HIV pre-exposure prophylaxis (PrEP) has offered the promise of limiting the global burden of HIV. The objective of this proposal is to conduct a pharmacokinetic (PK) study in transgender women to describe the pharmacokinetics of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as PrEP within this population.

Study Overview

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

Detailed Description

PrEP is a critical component of comprehensive transgender medical care. The proposed open-label, intensive PK study will inform the pharmacologic impact of combining PrEP and concurrent feminizing hormone regimens. The investigators hypothesize transgender women will achieve similar PrEP concentrations compared to the historical controls, and that hormone concentrations (estrogen and testosterone) will not be affected. The aims of this study are to (1) to determine if concurrent use of TDF/FTC as PrEP in combination with feminizing hormones alters the PK of tenofovir (TFV) and FTC and (2) to determine if concurrent use of PrEP with feminizing hormones alters serum estradiol and testosterone concentrations. To achieve these aims, this study will enroll transgender women who are receiving either oral/sublingual or transdermal estradiol with spironolactone. Using intensive PK sampling, plasma and intracellular TDF/FTC concentrations will be measured after 14 days of oral TDF/FTC.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
• Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Self identify as a transgender woman.
• Receiving estradiol (oral/sublingual tablets or transdermal patches) with oral spironolactone for at least 3 months prior to study entry.
• Serum estradiol level >100 pg/mL.
• Non-reactive 4th or 5th generation screening test for HIV.
• Adults (19 years or older).
• Able to read and speak English to ensure appropriate ability to obtain informed consent.

Exclusion Criteria:

• Participants will not be included in the study if one, or more, of the following criteria are met:
• Use of drugs known to be contraindicated with TDF, FTC, estradiol, or spironolactone within 30 days of study entry. The study team will review all concomitant medications at screening based on the US Department of Health and Human Services drug interaction table and the drug product labeling.
• Use of injectable estradiol (valerate or cypionate).
• Presence of any active condition or clinically significant disease that, in the investigator's opinion, would compromise the subject's safety or outcome of the study, including qualifying for non-occupational post-HIV exposure prophylaxis.
• Signs or symptoms of acute HIV infection within the last 30 days.
• Laboratory values obtained within 30 days prior to study entry:
• Creatinine clearance (CrCl) less than 60 mL/min as estimated by the Cockcroft-Gault equation.
• Positive hepatitis B surface antigen and/or hepatitis C antibody.
• Alanine transaminase (ALT), Aspartate transaminase (AST) or alkaline phosphatase > 5x the upper limit of normal (ULN).
• Hemoglobin <10 g/dL.
• Platelets <50,000/mm3.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TDF/FTC; Tenofovir Disoproxil Fumarate/Emtricitabine group HIV-uninfected transgender women receiving feminizing hormone therapy plus tenofovir disoproxil fumarate/emtricitabine	Drug: Tenofovir Disoproxil Fumarate/Emtricitabine; Participants will receive daily TDF/FTC for 14 days; Other Names: Descovy and Truvada

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TFV plasma exposure	Intensive PK sampling compared to historical controls	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FTC plasma exposure	Intensive PK sampling compared to historical controls	14 days
Tenofovir-diphosphate (TFV-DP) intracellular concentrations	Peripheral blood mononuclear cells (PBMC) concentrations compared to historical control	14 days
Emtricitabine-triphosphate (FTC-TP) intracellular concentrations	Peripheral blood mononuclear cells (PBMC) concentrations compared to historical control	14 days
TFV maximum plasma concentration (Cmax)	Cmax of TFV compared to historical control	14 days
FTC maximum plasma concentration (Cmax)	Cmax of FTC compared to historical control	14 days
Estradiol serum concentrations	Before and after intervention	14 days
Testosterone serum concentrations	Before and after intervention	14 days

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Kimberly Scarsi, PharmD, MS, University of Nebraska

Publications and helpful links

General Publications

• Cirrincione LR, Podany AT, Havens JP, Bares SH, Dyavar SR, Gwon Y, Johnson TM, Amoura NJ, Fletcher CV, Scarsi KK. Plasma and intracellular pharmacokinetics of tenofovir disoproxil fumarate and emtricitabine in transgender women receiving feminizing hormone therapy. J Antimicrob Chemother. 2020 May 1;75(5):1242-1249. doi: 10.1093/jac/dkaa016.

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2018
• Primary Completion (Actual): September 10, 2018
• Study Completion (Actual): September 10, 2018

Study Registration Dates

• First Submitted: August 23, 2017
• First Submitted That Met QC Criteria: August 30, 2017
• First Posted (Actual): September 1, 2017

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

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: 0491-17-FB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes