PrEP + Hormone Therapy for HIV Prevention in Transgender Women

Overseen By Jennifer H Hoffmann

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must be taking: PrEP

Must not be taking: Anticoagulants, Immunomodulators

Disqualifiers: Hepatitis B, Cardiac arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to use Truvada® for HIV prevention in transgender women taking feminizing hormones. It aims to determine the right dose of this medication when combined with hormone treatments like estradiol (a form of estrogen) or Lupron (a hormone therapy). Participants will take Truvada® daily and receive either hormone injections or pills to assess how the combination affects HIV prevention. This trial suits transgender women who are HIV-negative and not currently on hormone therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking research in HIV prevention.

Will I have to stop taking my current medications?

The trial requires participants to stop taking feminizing hormone therapies until certain testosterone levels are reached. Additionally, you must refrain from using aspirin, NSAIDs, and certain anticoagulants before and after study visits. The protocol does not specify other medication restrictions, but it's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Truvada, the main treatment in this trial, is generally safe and well-tolerated for preventing HIV. Approved by the FDA for pre-exposure prophylaxis (PrEP) since 2012, it has proven effective in various groups, including teenagers, pregnant individuals, and breastfeeding people. However, some serious side effects, such as a buildup of lactic acid in the blood and liver problems, have been reported.

The trial also includes treatments like Leuprolide and Estradiol. Leuprolide, a hormone injection, is commonly used and generally safe, though it can cause hot flashes and mood changes. Estradiol, a type of estrogen, is usually safe in prescribed amounts. Monitoring hormone levels is important to avoid high levels, which can be risky.

In summary, while Truvada and the hormones in this trial are known to be safe, they may have side effects. Participants should be aware of these potential issues and discuss any concerns with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine Truvada, a well-known HIV prevention medication, with hormone therapy options specifically for transgender women. This approach is different because it considers the unique needs of transgender women, who are often at higher risk for HIV but may face challenges with traditional prevention methods. By integrating hormone therapy, such as GnRH agonists and varying doses of estrogen, with PrEP, there is potential for improved adherence and efficacy. This combination could offer a more tailored and effective strategy for HIV prevention in this community, addressing both gender-affirming treatment and health protection simultaneously.

What evidence suggests that this trial's treatments could be effective for HIV prevention in transgender women?

Research shows that Truvada, when used as Pre-Exposure Prophylaxis (PrEP), effectively prevents HIV. This trial will evaluate Truvada alone and in combination with hormone therapies. Studies have found that PrEP works well for transgender women, even if they are taking hormones for gender transition. Truvada does not lower hormone levels, so it should remain effective during these treatments. In this trial, some participants will receive PrEP with either low or high doses of estradiol (a type of estrogen). While there might be a slight decrease in the drug's concentration, it typically stays above the level needed to protect against HIV. Overall, Truvada as PrEP is expected to be safe and effective for transgender women taking hormones. ^{6 7 8 9 10}

Who Is on the Research Team?

Mark A Marzinke, PhD

Principal Investigator

Johns Hopkins School of Medicine

Are You a Good Fit for This Trial?

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

Able and willing to provide adequate information for locator purposes

I can stop taking aspirin and NSAIDs one week before and after each biopsy.

Agree not to participate in other research studies involving drugs and/or medical devices for the duration of the study

Exclusion Criteria

I haven't used any immune system medications in the last 4 weeks and don't plan to during the study.

I have had symptoms or been diagnosed with a treatable rectal or urinary infection in the last 2 months.

I am currently taking medication that increases bleeding risk, like warfarin or high-dose aspirin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline Evaluation

Baseline visit with colon biopsies and kidney function testing

1 day

1 visit (in-person)

Treatment Phase 1: PrEP Only

Participants receive Truvada® once daily for 7 days to achieve steady state drug concentrations

1 week

1 intensive sampling visit (9 hours)

Treatment Phase 2: PrEP with GnRH Agonist

Participants receive depot leuprolide acetate (Lupron®) injection while on PrEP, followed by PK and PD sampling

2 weeks

1 intensive sampling visit (9 hours)

Treatment Phase 3: PrEP with Low Dose Estrogen

Participants begin low-dose oral estrogen therapy in conjunction with PrEP for 1 week

1 week

1 intensive sampling visit (9 hours)

Treatment Phase 4: PrEP with High Dose Estrogen

Participants transition to high-dose estrogen therapy while on PrEP for 1 week

1 week

1 intensive sampling visit (9 hours)

Post-Treatment Evaluation

PrEP is discontinued, and samples are collected to assess renal function and hormonal concentrations

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol
• Leuprolide
• Truvada

Trial Overview 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.

How Is the Trial Designed?

Group I: PrEP plus Low Dose Estrogen Experimental Treatment 1 Intervention

Truvada one tablet by mouth daily Estradiol 1 milligram by mouth daily x 2 weeks

Group II: PrEP plus High Dose Estrogen Experimental Treatment 1 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) Agonist Experimental Treatment 1 Intervention

Truvada one tablet by mouth daily Leuprolide 11.25 milligrams (mg) intramuscular (im) injection once

Group IV: High Dose Estrogen Experimental Treatment 1 Intervention

Estradiol 6 mg by mouth daily x 2 weeks

Group V: Pre-Exposure Prophylaxis (PrEP) only Active Control 1 Intervention

Truvada one tablet by mouth daily

Truvada is already approved in European Union, United States, Canada 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

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

PrEP (pre-exposure prophylaxis) has shown promise as an HIV prevention method, but clinical trials have often excluded or inadequately represented transgender women, limiting our understanding of their specific needs.

To effectively implement PrEP for transgender women, it is crucial to create gender-affirming healthcare environments and engage with trans communities to address barriers and enhance uptake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of PrEP among transgender women: the critical role of gender affirmation in research and clinical practices. Sevelius, JM., Deutsch, MB., Grant, R.[2023]

In the iPrEx study involving 2499 participants, PrEP with emtricitabine and tenofovir was found to be effective in preventing HIV acquisition among transgender women, but adherence to the medication was low, with only 18% of those in the PrEP group having detectable drug levels at the time of HIV testing.

Transgender women reported higher risk behaviors compared to men who have sex with men (MSM), yet the study indicated that PrEP use did not correlate with these risk behaviors, highlighting the need for tailored interventions to improve adherence in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial. Deutsch, MB., Glidden, DV., Sevelius, J., et al.[2018]

Transgender individuals, especially trans women of color, are at a significantly higher risk for HIV, highlighting the urgent need for effective prevention strategies like PrEP.

Barriers to PrEP uptake in the transgender community include limited access to healthcare and concerns about potential interactions with hormone therapy, which need to be addressed to improve prevention efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-Exposure Prophylaxis in Trans Populations: Providing Gender-Affirming Prevention for Trans People at High Risk of Acquiring HIV. Deutsch, MB.[2019]

Pre-exposure prophylaxis (PrEP) medications, specifically emtricitabine/tenofovir alafenamide (F/TAF) and emtricitabine/tenofovir disoproxil fumarate (F/TDF), are both effective in preventing HIV, with F/TAF showing non-inferior efficacy to F/TDF in a Phase 3 study involving at-risk populations.

F/TAF may be a safer alternative for individuals, particularly cisgender men and transgender women with existing bone or renal conditions, allowing for a more personalized approach to HIV prevention based on individual health profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Focused Selection of PrEP Medication for Individuals at Risk of HIV: A Narrative Review. Fields, SD., Tung, E.[2023]

Transgender populations in the USA have a high HIV prevalence of 13.7%, highlighting the urgent need for effective HIV prevention and treatment strategies tailored to their unique needs.

Current HIV prevention methods, like topical microbicides and PrEP, have not been adequately tested in transgender individuals, and concerns about drug-hormone interactions may affect their adherence to treatment, indicating a critical gap in research and healthcare provision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV Antiretroviral Treatment and Pre-exposure Prophylaxis in Transgender Individuals. Poteat, TC., Radix, A.[2021]

Tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) used for preexposure prophylaxis (PrEP) shows a low likelihood of drug interactions with cross-sex hormone therapies in transgender women, indicating it is safe for use in this population.

High adherence to PrEP has been associated with efficacy in preventing HIV among transgender women, but further research is needed to explore potential interactions and effects on HIV susceptibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic Considerations for Preexposure Prophylaxis in Transgender Women. Anderson, PL., Reirden, D., Castillo-Mancilla, J.[2020]

In a study involving eight transgender women and eight cisgender men, it was found that transgender women on gender-affirming hormone treatment had 32% lower plasma concentrations of the HIV PrEP medications tenofovir (TFV) and emtricitabine (FTC) compared to cisgender men, suggesting a potential interaction that could affect drug efficacy.

The reduction in TFV and FTC levels raises concerns about the effectiveness of daily PrEP in transgender women on hormone therapy, indicating that alternative dosing strategies may be necessary to ensure reliable HIV prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transgender women on oral HIV pre-exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men. Shieh, E., Marzinke, MA., Fuchs, EJ., et al.[2023]

In the iPrEx trial, preexposure prophylaxis (PrEP) with FTC/TDF effectively reduced HIV infections and syphilis rates among participants, indicating its efficacy as a preventive measure against HIV.

Despite some participants believing they were receiving FTC/TDF reporting more sexual partners, there was no evidence of increased risky sexual behavior (like unprotected anal intercourse) associated with PrEP use, suggesting that PrEP did not lead to risk compensation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No evidence of sexual risk compensation in the iPrEx trial of daily oral HIV preexposure prophylaxis. Marcus, JL., Glidden, DV., Mayer, KH., et al.[2022]

A clinical trial showed that the combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) can reduce HIV acquisition by 44% among men who have sex with men (MSM) and transgender women, with up to 90% effectiveness when taken daily.

Healthcare providers expressed optimism about prescribing PrEP but highlighted significant implementation challenges, such as the need for community education, monitoring adherence, and addressing patient demand, which was low at the time of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection. Arnold, EA., Hazelton, P., Lane, T., et al.[2022]

In a 48-week study involving 136 at-risk cisgender women, daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) was found to be effective in preventing HIV, with no new infections reported among participants.

Despite the effectiveness of TDF/FTC, adherence was a significant issue, as only 46% of participants remained on PrEP by the end of the study, highlighting the need for further investigation into the reasons for nonadherence and low retention rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a Pre-exposure Prophylaxis Demonstration Project for At-risk Cisgender Women in the United States. Blumenthal, J., Jain, S., He, F., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5111857/

HIV pre-exposure prophylaxis in transgender women TGW receiving PrEP had low drug concentrations, especially at times of potential HIV exposure, leading to no PrEP effectiveness among this subgroup.

2. eatg.org eatg.org/hiv-news/feminizing-hormones-dont-affect-prep-drug-levels/

Feminizing hormones don't affect PrEP drug levels “Our study suggests that oral PrEP is clinically effective among trans women with HIV risk on hormones,” said Vitoria Berg Cattani, MSc, a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05663892?term=AREA%5BInterventionSearch%5D(%22Estradiol%22)&rank=9

Drug-Drug Interaction Study in Trans Women Living With HIV The objective of this DDI study is to investigate the pharmacokinetic effects of the common feminizing hormone regimens (oral estradiol with an anti-androgen ( ...

4. aidsmap.com aidsmap.com/news/jul-2018/prep-does-not-lower-feminising-hormone-level-transgender-women

PrEP does not lower feminising hormone level in ... Tenofovir levels in the blood were reduced by 13% in trans women who used estradiol, but remained above the level shown to confer protection, ...

5. cdr.lib.unc.edu cdr.lib.unc.edu/downloads/xp68kt415

Impact of Feminizing Hormone Therapy in Transgender ... Transgender women are unique due to their combination of rectal HIV infection site and high estradiol concentrations.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5459979/

Pre-exposure prophylaxis for HIV prevention in women This narrative review summarizes the efficacy and safety data of PrEP in women, discusses considerations related to medication adherence for women who use PrEP,

7. bhiva.org bhiva.org/file/5bbc8c4e5ed86/AlisonRodger.pdf

Guidelines on the use of pre- exposure prophylaxis (PrEP) 87% women and 96% men had detectable drug levels at visits. • PREVENIR: Ongoing cohort, n=1435, 99% MSM at risk of HIV. Daily PrEP (44%, 302 PYFU): On-demand. ( ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10338392/

Estradiol and Spironolactone Plasma Pharmacokinetics ... Physiological female levels (100–200 pg/mL) served as a safety parameter for estradiol levels [10] to avoid levels above 200 pg/mL. Fifteen ...

9. prepwatch.org prepwatch.org/wp-content/uploads/2022/04/DPP-FAQs-April-2022.pdf

Frequently Asked Questions about the Dual Prevention Pill The Dual Prevention Pill (DPP) is a single, co-formulated, daily oral pill containing oral pre-exposure prophylaxis. (PrEP) and combined oral contraception ...

10. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.16097

Drug–drug interactions between gender‐affirming hormone ... PrEP is expected to be effective and safe in transpersons and should be provided to high-risk individuals regardless of gender affirming hormone ...