Clinical trial NCT03060785: Finding the Right Tenofovir/Emtricitabine Regimen for Pre-Exposure Prophylaxis (PrEP) in Transgender Women
Official title: Finding the Right Tenofovir/Emtricitabine Regimen for Pre-Exposure Prophylaxis (PrEP) in Transgender Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Prevention
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2017-02-23
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Colon tissue tenofovir diphosphate (TFV-DP)
timeFrame: One week
Secondary outcomes:
measure: Ex vivo colon explant HIV challenge
timeFrame: One week
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University Drug Development Unit
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Craig Hendrix, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.