Study of Truvada for HIV Pre Exposure Prophylaxis Using Daily Directly Observed Therapy to Look at Potential Interactions Between Truvada and Hormone Therapy
Condition: HIV Prevention; Transgender Health
Intervention: 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate
Intervention description: All study participants received daily observed therapy with FTC/TDF.
Intervention MeSH terms: Tenofovir; Emtricitabine
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Intervention model description: All participants will receive Truvada for study duration and will take pills using daily observed therapy.
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pre Exposure Prophylaxis; HIV prevention; Emtricitabine, Tenofovir Disoproxil Fumarate; transgender health; transgender persons; drug combination; androgens; estrogens; drug combinations; transmen; non binary; Truvada; daily observed therapy

Summary:

      Truvada (Emtricitabine or FTC and tenofovir disoproxil fumarate or TDF) has been approved for
      HIV prevention since 2012. Drug concentrations after receipt of oral Truvada for HIV Pre
      Exposure Prophylaxis (or PrEP) appeared to be lower in transgender women compared to Men who
      Have Sex with Men (MSM) in the iPrEx study, the landmark study of PrEP for HIV prevention.
      Concentrations were especially low among transgender women (TGW) reporting use of feminizing
      hormones. Reasons for the lower drug concentrations may be behavioral or biomedical, or a
      combination of both. While there are no systemic drug-drug interactions between TDF and oral
      contraception, there are known interactions involving these classes of medications with drug
      transporters that could affect drug concentrations in target tissues. Drug-drug interactions
      with natural estrogens and anti-androgenic agents used for gender affirming hormone therapy
      among transgender women have not been studied, neither have interactions between
      emtricitabine and female hormones. Concerns about the impact of PrEP on gender affirming
      hormone therapy is the main barrier for uptake of PrEP among transgender women. In addition,
      very little is known about TDF/FTC pharmacokinetics in transgender men using testosterone
      hormonal therapy. Drug-drug interactions with masculinizing hormones have never been properly
      investigated as trans gender men have not been formally involved in PrEP clinical trials or
      demonstrations projects.This small study will assess pharmacokinetic drug-drug interactions
      between tenofovir disoproxil fumarate/emtricitabine and cross-sex hormone therapy. The
      I-BrEATHe study is a substudy of the Triumph study, a culturally-relevant community-led PrEP
      demonstration project in transgender communities. The I- BrEATHe pharmacokinetic substudy
      will provide Truvada daily using directly observed therapy in 24 transgender women and 24
      transgender men over a one month period, and will measure drug and hormone therapy levels in
      blood collected from participants.
    

Eligibility criteria:

        Inclusion Criteria:

        All subjects:

          -  HIV antibody seronegative (negative HIV rapid test),

          -  18 years or older,

          -  Has a smart phone with access to two-way video call capability,

          -  Willingness to be contacted for a short call every day for 4 weeks,

          -  Adequate renal function (creatinine clearance ≥ 60 ml/min estimated by the Cockcroft
             Creatinine Clearance Formula),

          -  Provides written informed consent,

        For Transgender women:

          -  Male assigned sex at birth, and self-reported current gender identity as "woman" or
             "transgender women", or other trans-feminine spectrum identity,

          -  Current feminizing Hormone Therapy (HT) use for at least 6 months,

        For Transgender men:

          -  Female assigned sex at birth, and self-reported current gender identity as "man" or
             "transgender man", or other trans-masculine spectrum identity,

          -  Current masculinizing Hormone Therapy (HT) use for at least 6 months with testosterone

        Exclusion Criteria

          -  Expects to change or discontinue current HT use during the 4 weeks study period,

          -  Signs of symptoms of acute viral syndrome,

          -  Use of FTC or TDF in the past 90 days

          -  Receiving ongoing therapy with any of the following:

        AntiRetroviral Therapy, including nucleoside analogs, non-nucleoside reverse transcriptase
        inhibitors, protease inhibitors or investigational antiretroviral agents interferon (alpha,
        beta, or gamma) or interleukin (e.g., IL-2) therapy, aminoglycoside antibiotics,
        amphotericin B, cidofovir, systemic chemotherapeutic agents, other agents with significant
        nephrotoxic potential, other agents that may inhibit or compete for elimination via active
        renal tubular secretion (e.g., probenecid), and/or other investigational agents

          -  Renal insufficiency documented as Creatinine Clearance < 60 ml/min

          -  For masculine-spectrum identifying persons, positive pregnancy test at screening

          -  At enrollment, has any other condition or factor that, based on the opinion of the
             investigator or designee, would preclude provision of informed consent; make
             participation in the study unsafe; complicate interpretation of study outcome data; or
             otherwise interfere with achieving the study objectives.