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

HIV Prevention Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03270969
• Other study ID #: 0491-17-FB
• Status: Completed
• Phase: Phase 1
• Start date: January 5, 2018
• Est. completion date: September 10, 2018

Study information

• Verified date: September 2023
• Source: University of Nebraska
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: September 10, 2018
• Est. primary completion date: September 10, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Prevention

Intervention

Drug:
• Tenofovir Disoproxil Fumarate/Emtricitabine
Participants will receive daily TDF/FTC for 14 days

Locations

Country	Name	City	State
United States	University of Nebraska Medical Center	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
University of Nebraska

Country where clinical trial is conducted

United States, 

Outcome

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