Trial Summary
What is the purpose of this trial?This is a research study to determine the best way to dose Truvada®, an oral medication licensed to be taken as Pre-Exposure Prophylaxis (PrEP) to prevent HIV infection, in transgender women who are also taking feminizing hormones. The duration of the study is about 4 months, and involves a screening visit, a baseline visit with colon biopsies and kidney function testing, and several outpatient visits, including 5 intensive sampling visits that last about 9 hours and involve colon biopsies, kidney function testing and other blood specimen collections.
After the baseline visit, participants will start on PrEP, daily Truvada® pills, and will continue on the Truvada® for 5 weeks. Participants will then receive either an injection of Lupron, oral low-dose estradiol or oral high-dose estradiol, which will be taken along with the Truvada® PrEP for 1-2 weeks before returning for an intensive sampling visit.
What safety data exists for PrEP and hormone therapy in transgender women?Existing safety data suggests that PrEP (tenofovir disoproxil fumarate/emtricitabine) is effective for HIV prevention in transgender women, though they have been underrepresented in trials. Studies indicate no major drug interactions between PrEP and hormone therapy (estradiol, progestins, spironolactone), as they use different metabolic pathways. However, transgender women on hormone therapy may have lower concentrations of PrEP drugs compared to cisgender men, which could affect efficacy. More research is needed to fully understand these interactions and their impact on HIV prevention and hormone therapy goals.134710
Is the drug Truvada a promising option for preventing HIV in transgender women?Yes, Truvada is considered a promising option for preventing HIV in transgender women. It is part of a strategy called pre-exposure prophylaxis (PrEP), which has shown to be effective in reducing the risk of HIV infection in high-risk groups, including transgender women. While there are challenges in its use, such as ensuring access and addressing concerns about interactions with hormone therapy, Truvada remains a key part of HIV prevention efforts.35689
What data supports the idea that PrEP + Hormone Therapy for HIV Prevention in Transgender Women is an effective treatment?The available research shows that PrEP, a drug combination of emtricitabine and tenofovir disoproxil fumarate, can reduce the risk of getting HIV by up to 90% if taken daily. This was demonstrated in a study involving transgender women and men who have sex with men. However, there are challenges like low uptake and adherence to PrEP among transgender women, partly due to concerns about interactions with hormone therapy. Despite these challenges, PrEP remains a promising option for HIV prevention in transgender women.12368
Do I have to stop taking my current medications to join the trial?The trial requires that you are not currently taking any gender affirming hormonal therapy (GAHT) or are willing to stop until your testosterone levels are ≥ 200 ng/dL. You must also not be on any PrEP regimen. Additionally, you cannot use warfarin, heparin, or other anticoagulants, and must refrain from systemic or anorectal immunomodulatory medications within 4 weeks of enrollment.
Eligibility Criteria
This trial is for transgender women over 18, not currently on PrEP or GAHT with testosterone ≥200 ng/dL. Participants must be HIV-negative, English-speaking, and willing to avoid certain medications and activities before/after biopsies. They should agree to use condoms and participate in a directly observed study.Inclusion Criteria
I am 18 years old or older.
I identify as a transgender woman.
I can communicate in English.
Exclusion Criteria
I haven't used any immune system medications in the last 4 weeks and don't plan to during the study.
I am currently taking medication that increases bleeding risk, like warfarin or high-dose aspirin.
I have a lab result that shows a significant abnormality.
I am not taking any PrEP medications.
I have had serious bleeding in my stomach or intestines.
I have had a serious heart or lung problem recently.
I have a serious heart rhythm problem or kidney disease with low creatinine clearance.
Treatment Details
The study tests how Truvada as PrEP interacts with gender-affirming hormones in transgender women. It involves taking Truvada alone or with Leuprolide or low/high-dose Estradiol for about 4 months, including intensive sampling visits with colon biopsies and kidney function tests.
5Treatment groups
Experimental Treatment
Active Control
Group I: PrEP plus Low Dose EstrogenExperimental Treatment1 Intervention
Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks
Group II: PrEP plus High Dose EstrogenExperimental Treatment1 Intervention
Truvada one tablet by mouth daily Estradiol 6 milligrams (mg) by mouth daily x 2 weeks
Group III: PrEP plus Gonadotropin Releasing Hormone (GnRH) AgonistExperimental Treatment1 Intervention
Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once
Group IV: High Dose EstrogenExperimental Treatment1 Intervention
Estradiol 6 mg by mouth daily x 2 weeks
Group V: Pre-Exposure Prophylaxis (PrEP) onlyActive Control1 Intervention
Truvada one tablet by mouth daily
Truvada is already approved in European Union, United States, Canada, Australia for the following indications:
🇪🇺 Approved in European Union as Truvada for:
- HIV pre-exposure prophylaxis
🇺🇸 Approved in United States as Truvada for:
- HIV pre-exposure prophylaxis
🇨🇦 Approved in Canada as Truvada for:
- HIV pre-exposure prophylaxis
🇦🇺 Approved in Australia as Truvada for:
- HIV pre-exposure prophylaxis
Find a clinic near you
Research locations nearbySelect from list below to view details:
Johns Hopkins School of Medicine Drug Development UnitBaltimore, MD
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Who is running the clinical trial?
Johns Hopkins UniversityLead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)Collaborator
References
A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection. [2022]A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States.
No evidence of sexual risk compensation in the iPrEx trial of daily oral HIV preexposure prophylaxis. [2022]Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior.
HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial. [2018]Pre-exposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate is used to prevent the sexual acquisition of HIV in groups at high risk such as transgender women. We used data from the iPrEx study to assess PrEP efficacy, effectiveness, and adherence in transgender women.
Pharmacologic Considerations for Preexposure Prophylaxis in Transgender Women. [2020]Studies of tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC)-based preexposure prophylaxis (PrEP) have not focused on transgendered women who are at disproportionate risk of HIV acquisition. Concerns exist for drug interactions between cross-sex therapy (estradiol, progestins, and spironolactone) with tenofovir disoproxil fumarate-emtricitabine. This review assessed the experimental and theoretical risk for such drug interactions. It was found that none of these medications are implicated as major perpetrators of drug interactions, and the classes use different metabolic pathways for clearance, suggesting a low likelihood for interactions in either direction. Subanalyses of transgender women in Preexposure Prophylaxis Initiative suggested PrEP efficacy if adherence was high. Nevertheless, several research gaps were identified, particularly the need for controlled interaction studies in transgendered women, including effects on renal clearance, intracellular tenofovir diphosphate and emtricitabine triphosphate in target cells, as well as hormone effects on HIV susceptibility and immunity. PrEP should continue to be offered to transgender women while additional research is planned or pending.
The future of PrEP among transgender women: the critical role of gender affirmation in research and clinical practices. [2023]Globally, transgender ("trans") women are one of the key populations most disproportionately impacted by HIV. Pre-exposure prophylaxis (PrEP) is the newest and most promising biomedical HIV prevention intervention to date. This paper reviews relevant literature to describe the current state of the science and describes the potential role of PrEP among trans women, including a discussion of unique considerations for maximizing the impact of PrEP for this vulnerable population.
Pre-Exposure Prophylaxis in Trans Populations: Providing Gender-Affirming Prevention for Trans People at High Risk of Acquiring HIV. [2019]Transgender (trans) people, particularly trans women of color, face alarmingly high rates of HIV. HIV pre-exposure prophylaxis (PrEP) with daily coformulated emtricitabine and tenofovir disoproxil fumarate is a promising biomedical HIV prevention modality; however, it has not yet been shown to be efficacious in the transgender population due to data limitations. Initial data suggest that barriers exist to PrEP uptake in the trans community, including lack of access to healthcare and concerns about interactions with hormone therapy. This article discusses these factors and reviews considerations for enhancing PrEP uptake and adherence in trans people at risk for HIV.
Transgender women on oral HIV pre-exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men. [2023]Oral HIV Pre-Exposure Prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective. Transgender women (TGW) have increased HIV risk, but have been underrepresented in trials. For TGW on oestrogens for gender-affirming hormone treatment (GAHT), TDF/FTC-oestrogen interactions may negatively affect HIV prevention or gender-affirming goals. Our aim was to evaluate any pharmacokinetic drug-drug interaction between GAHT and TDF/FTC.
HIV Antiretroviral Treatment and Pre-exposure Prophylaxis in Transgender Individuals. [2021]HIV prevalence is elevated among transgender populations with an estimated 13.7% of transgender adults living with HIV in the USA. In addition, transgender people experience significant disparities in biomedical HIV prevention and treatment. The efficacy of topical microbicides for prevention of HIV acquisition have not been tested among transgender people and may be impacted by hormonal therapies and/or surgeries undertaken by some transgender people to align their anatomy with their gender identity. Low pre-exposure prophylaxis (PrEP) uptake and adherence as well as potential drug-hormone interactions impact the efficacy of PrEP among transgender women. Few transgender men have been engaged in the PrEP continuum, and they have been largely excluded from PrEP research until very recently. Prioritisation of hormone therapy over HIV treatment as well as concerns about drug-hormone interactions may impact transgender women's adherence to antiretroviral therapy. More research is needed to clarify the clinical significance of identified drug-hormone interactions and better inform interventions to improve HIV prevention and care for transgender people.
Patient-Focused Selection of PrEP Medication for Individuals at Risk of HIV: A Narrative Review. [2023]Pre-exposure prophylaxis (PrEP) medication is a key component of the HIV prevention strategy in the US, which has been demonstrated to be highly effective in preventing HIV acquisition among individuals at risk. Two PrEP medications are currently approved: emtricitabine/tenofovir disoproxil fumarate (Truvada®; F/TDF) was approved by the US Food and Drug Administration in 2012, followed by emtricitabine/tenofovir alafenamide (Descovy®; F/TAF) in 2019. An ongoing randomized, double-blind, Phase 3 study (DISCOVER) demonstrated that F/TAF had non-inferior efficacy to F/TDF. While both medications have been found to be efficacious and well tolerated, several studies have identified that important differences exist with regards to pharmacokinetics, bone and renal safety profiles, and other factors. In this narrative review, we conducted a comprehensive evaluation of the populations at risk of HIV who may also be affected by, or at risk of, bone or renal conditions. We reviewed the safety profiles of F/TDF and F/TAF to develop an evidence-based algorithm for selecting the appropriate PrEP medication, based on biological, behavioral, and health characteristics of an individual at risk of HIV, and considered how the choice of PrEP medication may or may not compound safety concerns for these individuals. We identified that the introduction of F/TAF provides a valuable alternative to F/TDF, allowing the personalization of PrEP. F/TAF may be the preferred medication for cisgender men and transgender women at risk of HIV infection who are predisposed to, or already have, bone or renal conditions. While the approval of F/TAF is the first step in personalization of PrEP, additional options are still warranted to help accommodate the wide spectrum of individuals at risk of HIV with different lifestyles, medical histories, preferences, and requirements.
Results from a Pre-exposure Prophylaxis Demonstration Project for At-risk Cisgender Women in the United States. [2022]Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is effective for reducing human immunodeficiency virus (HIV) acquisition among cisgender women. We report results from the first US observational open-label demonstration project of pre-exposure prophylaxis (PrEP) among at-risk cisgender women.