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

Phase 1
Completed
Conditions
HIV Prevention
Interventions
Registration Number
NCT03270969
Lead Sponsor
University of Nebraska
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
15
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TDF/FTCTenofovir Disoproxil Fumarate/EmtricitabineTenofovir Disoproxil Fumarate/Emtricitabine group HIV-uninfected transgender women receiving feminizing hormone therapy plus tenofovir disoproxil fumarate/emtricitabine
Primary Outcome Measures
NameTimeMethod
TFV plasma exposure14 days

Intensive PK sampling compared to historical controls

Secondary Outcome Measures
NameTimeMethod
Emtricitabine-triphosphate (FTC-TP) intracellular concentrations14 days

Peripheral blood mononuclear cells (PBMC) concentrations compared to historical control

TFV maximum plasma concentration (Cmax)14 days

Cmax of TFV compared to historical control

FTC plasma exposure14 days

Intensive PK sampling compared to historical controls

Tenofovir-diphosphate (TFV-DP) intracellular concentrations14 days

Peripheral blood mononuclear cells (PBMC) concentrations compared to historical control

FTC maximum plasma concentration (Cmax)14 days

Cmax of FTC compared to historical control

Estradiol serum concentrations14 days

Before and after intervention

Testosterone serum concentrations14 days

Before and after intervention

Trial Locations

Locations (1)

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

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