Sex Hormone Therapy and Mucosal Tissues
Condition: Hiv
Study type: Observational

Summary: 
      The purpose of this research study is to better understand how sex hormone therapy that is
      used to treat women for menopausal symptoms, men with low testosterone, or as hormone therapy
      for transgender women, affects a class of medications called NRTIs (nucleoside reverse
      transcriptase inhibitors) used to treat and prevent HIV infection. The two most commonly used
      NRTIs are tenofovir and emtricitabine, which are the components of the drug Truvada and also
      included in the combination products Atripla, Complera, and Stribild. The medication's
      ability to work effectively may be altered when someone is also taking sex hormone therapy.

      In order to determine this effect, samples will be collected from some parts of the body
      where HIV makes copies. These samples will be measured for the levels of HIV medication, HIV
      virus and sex hormones that are present. The samples that will be looked at in this study
      include blood, cells from the vagina, semen, and tissue biopsies from the female genital
      tract and rectum.
    

Detailed description: 
      Study Design:

      This is an observational study of tenofovir/emtricitabine (TFV/FTC) concentrations in the
      genital and lower gastrointestinal tracts. Participants will be selected on the basis of
      receiving TFV/FTC as part of their ongoing HIV care. After participant education, informed
      consent, and screening for study eligibility, participants will be evaluated at baseline. All
      samples will be collected over the course of an outpatient sampling visit.

      Study Sampling:

        1. A blood sample will be collected to measure the concentration of TFV/FTC in the blood
           plasma, the concentration of TFV/FTC active metabolite concentrations (TFVdp/FTCtp) in
           the PBMCs, and the concentration of sex hormones in the blood stream.

        2. Vaginal and cervical tissue will be collected (for cisgender women) to measure for
           concentrations of TFVdp/FTCtp, HIV RNA, and estrogen/progesterone.

        3. Rectal tissue samples will be collected to measure for concentrations of TFVdp/FTCtp,
           HIV RNA, estrogen/progesterone (for cisgender and transgender women), and testosterone
           (for cisgender men).

        4. A semen sample will be collected (for cisgender men) to measure the concentrations of
           TFV/FTC, HIV RNA and testosterone.

      Pharmacokinetic Analysis:

      All blood, cervical, vaginal, semen and rectal tissue samples will be analyzed by the
      Clinical Pharmacology and Analytical Chemistry Laboratory (CPAC) at the UNC School of
      Pharmacy. TFV/FTC will be measured in blood and seminal plasma and TFVdp/FTCtp will be
      measured in PBMCs, SMCs using validated LC-MS/MS methods. HIV RNA will be measured in blood
      and seminal plasma using the Abbott Real Time HIV-1 quantitative assay. HIV RNA within the
      cervical and seminal cells and rectal tissues will be measured using an established Droplet
      Digital PCR method. Estradiol and progesterone will be measured in serum using validated
      florescent immunoassays.
    

Intervention name(s): Anoscopy with Rectal Tissue Sampling; Phlebotomy; Female Genital Tract Sampling
Intervention type(s): Procedure; Procedure; Procedure
Intervention description(s): All subjects will provide 10 pieces of rectal tissue; • Procedure: Blood plasma/serum collection Approximately 17 mL of blood will be taken from each subject just prior to tissue sampling.; Cohorts B only will have cervical cells, cervical tissue, and vaginal tissue collected
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This study will consist of 20 HIV positive men and women between 18-65 years of age
        (inclusive) with an intact gastrointestinal tract, uterus/cervix (if cisgender women), and
        male genital tract (if cisgender man) who are available to complete all study procedures at
        UNC.
      
Keywords: Hormones, Transgender