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

Phase 1
Completed
Conditions
HIV Prevention
Interventions
Registration Number
NCT03060785
Lead Sponsor
Johns Hopkins University
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TFV/FTC dosing in Transgender womenTenofovir Disoproxil Fumarate/EmtricitabineSingle daily dose of oral Tenofovir Disoproxil Fumarate/Emtricitabine (Truvada)for 7days in transgender women taking feminizing hormones
TFV/FTC dosing in Cis menTenofovir Disoproxil Fumarate/EmtricitabineSingle daily dose of oral Tenofovir Disoproxil Fumarate/Emtricitabine (Truvada) for 7days in cis men
Primary Outcome Measures
NameTimeMethod
Colon tissue tenofovir diphosphate (TFV-DP)One week

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).

Secondary Outcome Measures
NameTimeMethod
Ex vivo colon explant HIV challengeOne week

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).

Trial Locations

Locations (1)

Johns Hopkins University Drug Development Unit

🇺🇸

Baltimore, Maryland, United States

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