I-BrEATHe - Interactions Between Antiretrovirals And Transgender Hormones
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Tenofovir Diphosphate Concentration in Dried Blood Spots (DBS)
Study Overview
Brief 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.
Detailed Description
BACKGROUND The TRIUMPH study, or trans Research-Informed communities United in the Mobilization for the Prevention of HIV, is a new study responding to a pressing need for culturally-relevant community-led pre-exposure prophylaxis (PrEP) programs for transgender communities, especially for trans women of color who are most affected by the HIV epidemic. The TRIUMPH study will strive to identify the most effective PrEP service provision strategies which take into account the particular facilitators and barriers that transgender communities encounter in the health care system. To date, transgender women included in HIV prevention studies have been lumped into the larger aggregate of Men who have sex with Men (MSM) without taking into account the unique sociocultural context of transgender women. The TRIUMPH study will also include transgender men and other members of various transgender communities. The TRIUMPH project's goal is to identify the best methods to deliver PrEP safely and effectively to transgender communities while achieving the highest levels of adherence possible.
PrEP is the newest and most promising biomedical HIV prevention intervention yet developed and tested. The first clinical trial of PrEP ('iPrEx' or iniciativa Profilaxis Pre-Exposición) included MSM and transgender women who were at higher risk for HIV infection, and found that daily oral Truvada PrEP reduced the risk of HIV acquisition by 44% on an intention to treat basis. However, a sub-analysis of the iPrEx data conducted by Deutsch et al , found zero effectiveness on an intention to treat basis among the small subgroup of transwomen in the study. Further analyses revealed that the subgroup of trans women in iPrEx who were using hormones were less likely to have protective drug levels than those trans women not on hormones (OR 0.14, p<0.001). It is unclear if this difference is behavioral (less drug uptake) or biomedical (drug-drug interactions) in nature, or due to some combination of these factors, given the lack of pharmacokinetic (PK) studies testing for interactions between cross-sex hormone therapy (HT) and TDF/FTC, the active ingredients of Truvada. While there are studies of systemic drug-drug interactions between oral contraceptives and TDF, no such studies have been done with FTC, and no studies have been done with gender affirming HT, which differs from hormonal contraception in several respects. Drug-drug interactions with bioidentical 17-beta estradiol used for gender affirming hormone therapy among transgender women have not been studied.
The Interactions BEtween Antiretrovirals And Transgender Hormones, or I-BrEATHe study, is a sub study of the TRIUMPH study. I-BrEATHe will address one of the secondary aims of the TRIUMPH study which is to assess the pharmacokinetic drug-drug interactions between cross-sex HT and daily oral FTC/TDF.
Given that there are no PrEP studies to date that have specifically enrolled trans identified men, or have looked at the interactions between masculinizing HT and FTC/TDF, I-BrEATHe will enroll both transgender women and men. Transgender men report sexual rapport without condoms both vaginally and anally (range 26-60%), exhibit patterns of Sexually Transmitted Infections (STI) transmission and unwanted pregnancies. Transgender men also report use of sex for gender affirmation. Small convenience samples show that HIV prevalence is between 2- 5%. To date, there are no programs or PrEP recommendations specific for transgender men.
Overview of Previous Clinical Studies of PrEP There have been a large number of trials conducted with Truvada PrEP, including several demonstration projects. While there is no evidence to suggest that TDF/FTC interacts with commonly used feminizing or masculinizing hormone regimens, and evidence from studies of Antiretroviral (ARV) interactions with hormonal contraceptives have been reassuring, no direct study of these interactions has been conducted to date.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Exclusion Criteria
- Not provided
Arms & Interventions
TRUVADA DOT
one tablet containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate as single dose with daily observed therapy performed either via video calling, or at study visit, for a total of 28 to 30 days
Intervention: 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate (Drug)
Outcomes
Primary Outcomes
Tenofovir Diphosphate Concentration in Dried Blood Spots (DBS)
Time Frame: After 4 weeks of daily observed dosing of FTC/TDF
Tenofovir diphosphate concentration in dried blood spots at week 4
Secondary Outcomes
No secondary outcomes reported