PrEP + Hormone Therapy for HIV Prevention in Transgender Women

Recruiting in Palo Alto (17 mi)

Overseen by Mark A Marzinke, PhD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Johns Hopkins University

Must be taking: PrEP

Must not be taking: Anticoagulants, Immunomodulators

Disqualifiers: Hepatitis B, Cardiac arrhythmia, others

No Placebo Group

Approved in 4 Jurisdictions

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.

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.

What data supports the effectiveness of the drug PrEP with hormone therapy for HIV prevention in transgender women?

Research shows that PrEP, which includes the drugs emtricitabine and tenofovir disoproxil fumarate, can reduce the risk of HIV by up to 90% when taken daily, especially in high-risk groups like transgender women. However, there are concerns about how hormone therapy might interact with PrEP, and more research is needed to fully understand these interactions and improve HIV prevention in transgender women. ^{1 2 3 4 5}

Is PrEP with hormone therapy safe for transgender women?

Research suggests that PrEP (tenofovir disoproxil fumarate/emtricitabine) is generally safe for transgender women, with no major drug interactions found between PrEP and hormone therapy. However, more studies are needed to fully understand the interactions and effects on HIV prevention and hormone treatment goals. ^{1 2 6 7 8}

How is the drug Truvada unique for HIV prevention in transgender women?

Truvada is unique for HIV prevention in transgender women because it combines two medications, emtricitabine and tenofovir disoproxil fumarate, to prevent HIV, and it is being studied specifically for its effectiveness and safety when used alongside hormone therapy, which is important for transgender women. ^{1 3 5 9 10}

Research Team

Mark A Marzinke, PhD

Principal Investigator

Johns Hopkins School of Medicine

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

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Estradiol (Estrogen)
• Leuprolide (Gonadotropin-Releasing Hormone (GnRH) Agonist)
• Truvada (Antiretroviral Agent)

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.

Participant Groups

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 Canada for the following indications:

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+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Dr. Jeanne Marrazzo

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Executive Officer since 2023

MD, MPH

Dr. H. Clifford Lane

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Medical Officer

MD

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

HIV Antiretroviral Treatment and Pre-exposure Prophylaxis in Transgender Individuals. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

No evidence of sexual risk compensation in the iPrEx trial of daily oral HIV preexposure prophylaxis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. Switzerland 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Results from a Pre-exposure Prophylaxis Demonstration Project for At-risk Cisgender Women in the United States. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Pharmacologic Considerations for Preexposure Prophylaxis in Transgender Women. [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

The future of PrEP among transgender women: the critical role of gender affirmation in research and clinical practices. [2023]