Quantification of Estradiol's Impact on Nucleotides in Cellular Populations of the Lower GI Tract
Condition: HIV/AIDS
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Purpose: To Assess the impact of high and low in vivo estradiol exposure on PrEP
      (Pre-exposure prophylaxis) nucleotide concentrations in different cellular populations of the
      lower GI (gastrointestinal) tract and to quantify the relationship between estradiol,
      progesterone, and testosterone on PrEP nucleotide concentrations in rectal and peripheral
      blood mononuclear cells. As well as the relationship between estradiol, progesterone, and
      testosterone on PrEP concentrations in plasma.

      Participants: Healthy, cisgender female, volunteers, aged 18-49 inclusive on the date of
      screening with an intact gastrointestinal system and regular menstrual cycle.

      Procedures (methods): Participants will take a single daily dose of study drug for five days
      before each sampling visit. The visits will be scheduled during the early follicular phase of
      the menstrual cycle (approximately days 2-5 after the first day of menses, Visit 1) when
      estradiol is predicted to be the lowest and the late follicular phase (approximately days
      12-15 after the first day of menses, Visit 2) when estradiol is predicted to be highest.
      Samples of blood, rectal cells, and rectal tissue will be collected at both Visits 1 and 2.
      All participants will complete a follow-up safety visit within 14 days of completing study
      sampling.
    

Detailed description: 
      Participants will be enrolled, and sampling visits will be scheduled to correspond with their
      menstrual cycles. Five days prior to the first scheduled sampling visit, participants will
      come to the clinic to have a repeat urine pregnancy test performed to verify eligibility.
      After verification, participants will be given a single dose of the study medication,
      Truvada®. Study staff will witness the dose and assess for any adverse reactions post dose.
      Participants will be sent home with a supply of 4 additional doses of Truvada® for them to
      take at scheduled times for the next 4 days with study staff observing via video call. Study
      staff will assess for adverse events during each dosing call. Starting 72 hours before each
      sampling visit, participants will be required to switch to a low fiber diet and abstain from
      inserting anything rectally. Twelve hours prior to each sampling visit, participants will be
      required to abide by a clear liquid diet. Participants will be seen as an outpatient at the
      Clinical Translational Research Center (CTRC) at University of North Carolina at Chapel Hill
      (UNC) for these sampling visits. At these visits, participants will have blood samples drawn
      to measure peripheral blood mononuclear cells and serum hormone concentrations. Participants
      will also have rectal cells collected via cytobrush and rectal tissue collected via rectal
      biopsy. After all samples have been collected, participants will be evaluated for adverse
      events and be discharged. Within 14 days of completion of the second sampling visit, for a
      follow-up visit. At this visit, blood will be obtained to check safety labs.
    

Intervention name(s): Tenofovir 300Mg Oral Tablet; Emtricitabine 200 MG
Intervention type(s): Drug; Drug
Intervention description(s): Once daily dose of the combo tab x 5 days pre-sampling; Once daily dose of the combo tab x 5 days pre-sampling
Other intervention name(s): Truvada; Truvada
Intervention MeSH terms: Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science