Estradiol Therapy for HIV in Transgender Women

(GET IT RIgHT Trial)

Recruiting in Palo Alto (17 mi)

+26 other locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Antiretrovirals

Must not be taking: Estrogen therapy

Disqualifiers: Clotting disorders, Liver disease, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Transgender women (TW) are a key population and priority for HIV treatment. More research is needed to develop evidence-based clinical guidance when it comes to choosing antiretroviral treatment (ART) regimens for TW on feminizing hormonal therapy (FHT). Concerns about ART interacting with FHT and decreasing its effectiveness can lead to decreased ART adherence and increased viral loads. The GET IT RiGHT trial aims to address concerns about drug-drug interactions (DDIs) between ART and FHT while providing access to hormonal therapy to TW living with HIV. Data suggest that access to FHT improves adherence to HIV treatment and decreases treatment interruptions. This is an open-label, non-randomized, 3-group trial of adult TW and other individuals identifying as female or transfeminine but with male sex assigned at birth living with HIV. Participants will be on ART at entry and receive study-supplied 17-β estradiol for FHT for 48 weeks. The primary objectives of the study are to 1) assess whether TW continue to achieve therapeutic concentrations of ART while receiving FHT for 48 weeks and 2) assess whether serum estradiol concentrations on FHT (across a range of estradiol doses) vary between boosted and un-boosted ART regimens.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable antiretroviral therapy (ART) regimen for at least 28 days before joining and cannot change it during the study. You also need to avoid using any non-study provided feminizing hormonal therapy (FHT) and anti-androgens for the first 24 weeks.

What data supports the effectiveness of the drug Estradiol for HIV in transgender women?

Estradiol is a key component of feminizing hormone therapy, which is important for transgender women. However, concerns about interactions with HIV medications can affect how these drugs are taken, potentially impacting their effectiveness. ^{1 2 3 4 5}

Is estradiol therapy generally safe for transgender women with HIV?

Estradiol therapy is generally considered safe for transgender women, but there can be interactions with HIV medications that may affect how the body processes the hormone. It's important to work closely with healthcare providers to manage these interactions and ensure both treatments are effective. ^{1 2 3 6 7}

How is the drug Estradiol unique for HIV treatment in transgender women?

Estradiol is unique for HIV treatment in transgender women because it is part of feminizing hormone therapy (FHT) that helps align their physical characteristics with their gender identity, which is crucial for their overall well-being. However, it can interact with antiretroviral therapies (ARTs) like efavirenz, affecting its metabolism and potentially complicating HIV treatment. ^{2 3 4 5 8}

Eligibility Criteria

This trial is for adult transgender women and transfeminine individuals living with HIV who have been on antiretroviral therapy (ART) for at least 24 weeks. They must have a stable viral load, normal organ function tests, no history of certain cancers or clotting disorders, and not be taking other hormone therapies outside the study.

Inclusion Criteria

I was assigned male at birth and identify as a woman or transfeminine.

I have been on HIV medication for at least 24 weeks and on a stable regimen for the last 28 days.

I have been on the same HIV medication for at least 28 days and don't plan to change it.

Exclusion Criteria

I do not have any health conditions that make it unsafe for me to receive hormone therapy.

I have had breast cancer or carry the BRCA gene mutation.

I have or had hepatitis B or currently have active hepatitis C.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive study-supplied 17-β estradiol for feminizing hormonal therapy (FHT) while continuing their antiretroviral therapy (ART) for 48 weeks.

48 weeks

Visits at weeks 0, 4, 12, 24, 36, and 48

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Intensive PK Sampling

Intensive pharmacokinetic (PK) sampling to assess ART and 17-β estradiol exposure at weeks 0, 24, and 48.

48 weeks

3 intensive PK visits

Treatment Details

Interventions

• Estradiol (Hormone Therapy)

Trial Overview The GET IT RiGHT trial studies how well HIV treatment works when taken alongside feminizing hormone therapy (FHT), specifically estradiol. It checks if ART maintains its effectiveness and measures estradiol levels in participants over a period of 48 weeks.

Participant Groups

Group I: Group 3: Boosted DRV-treated Experimental Treatment 1 Intervention

Participants taking any regimen containing darunavir plus cobicistat (DRV/c)

Group II: Group 2: DTG-treated Experimental Treatment 1 Intervention

Participants taking dolutegravir (DTG) once daily + tenofovir disoproxil fumarate (TDF) + (FTC or lamivudine \[3TC\])

Group III: Group 1: BIC-treated Experimental Treatment 1 Intervention

Participants taking bictegravir (BIC) + tenofovir alafenamide (TAF) + emtricitabine (FTC)

Estradiol is already approved in European Union, United States, Canada for the following indications:

🇪🇺 Approved in European Union as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

🇺🇸 Approved in United States as Estradiol for:

• Moderate to severe vasomotor symptoms due to menopause
• Vulvar and vaginal atrophy due to menopause
• Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
• Prevention of postmenopausal osteoporosis
• Palliative treatment of breast cancer
• Palliative treatment of prostate cancer

🇨🇦 Approved in Canada as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Northwestern University CRS (Site #2701) Chicago, IL

The Ponce de Leon Center CRS (5802) Atlanta, GA

University of Colorado Hospital CRS (6101) Aurora, CO

University of California, San Francisco HIV/AIDS CRS (801) San Francisco, CA

More Trial Locations

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID) Lead Sponsor

References

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

Transgender Women Living with HIV Frequently Take Antiretroviral Therapy and/or Feminizing Hormone Therapy Differently Than Prescribed Due to Drug-Drug Interaction Concerns. [2020] Both hormone therapy (HT) and antiretroviral therapy (ART) can be lifesaving for transgender women (TW) living with HIV, but each has side effects and potential drug-drug interactions (DDI). We assessed how concerns about HT-ART interactions affect treatment adherence.

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

The Effect of Efavirenz on Estradiol Metabolism in Transgender Women. [2020] The goal of hormonal therapy in treating gender dysphoria is to maintain cross-sex hormone levels in the normal physiological range for the desired gender. Estrogen is the mainstay of hormonal therapy for male to female transgender patients. Efavirenz, a non-nucleoside reverse-transcriptase inhibitor, has been one of the most commonly prescribed antiretroviral therapies (ARTs). However, this regimen has also given rise to the most clinically significant drug-drug interactions between ARTs and hormone-based contraceptives. We discuss here three transgender HIV-positive women in whom efavirenz effected the metabolism of orally administered estradiol (and probably medroxyprogesterone).

3. Switzerland pubmed.ncbi.nlm.nih.gov

Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices. [2022] Studies have shown that transgender women (TGW) are disproportionately affected by HIV, with an estimated HIV prevalence of 19.1% among TGW worldwide. After receiving a diagnosis, HIV-positive TGW have challenges accessing effective HIV treatment, as demonstrated by lower rates of virologic suppression and higher HIV-related mortality. These adverse HIV outcomes have been attributed to the multiple sociocultural and structural barriers that negatively affect their engagement within the HIV care continuum. Guidelines for feminizing hormonal therapy among TGW recommend combinations of oestrogens and androgen blockers. Pharmacokinetic studies have shown that certain antiretroviral therapy (ART) agents, such as protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and cobicistat, interact with ethinyl estradiol, the key oestrogen component of oral contraceptives (OCPs). The goal of this article is to provide an overview of hormonal regimens used by TGW, to summarize the known drug-drug interactions (DDIs) between feminizing hormonal regimens and ART, and to provide clinical care recommendations.

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

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.

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

Gender affirmative HIV care framework: Decisions on feminizing hormone therapy (FHT) and antiretroviral therapy (ART) among transgender women. [2023] Integration of feminizing hormone therapy (FHT) and antiretroviral therapy (ART) is critical in providing gender-affirming HIV care for transgender (trans) women living with HIV. However, interpersonal communications with HIV providers who are not competent with FHT may complicate this integration.

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

Drug-drug Interactions Among Thai Transgender Women Living with Human Immunodeficiency Undergoing Feminizing Hormone Therapy and Antiretroviral Therapy: The iFACT Study. [2021] Drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are a major concern among transgender women (TGW), which may lead to suboptimal ART adherence and inappropriate FHT dosage. To evaluate potential drug-drug interactions between FHT and ART, we performed intensive measurements of the pharmacokinetic (PK) parameters of blood tenofovir (TFV), efavirenz (EFV), and estradiol (E2).

7. England pubmed.ncbi.nlm.nih.gov

Feminizing hormone therapy in a Canadian cohort of transgender women with and without HIV. [2023] Potential bidirectional drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are of concern for trans women with HIV and their healthcare providers. This study aimed to characterize patterns of FHT and ART among trans women with HIV and to compare serum hormone levels to trans women without HIV.

8. England pubmed.ncbi.nlm.nih.gov

Plasma and intracellular pharmacokinetics of tenofovir disoproxil fumarate and emtricitabine in transgender women receiving feminizing hormone therapy. [2022] Transwomen have an increased risk of HIV acquisition compared with other adults. Drug-drug interactions between pre-exposure prophylaxis (PrEP) and gender-affirming therapy are cited as a reason for poor PrEP uptake among transwomen. We evaluated plasma tenofovir and emtricitabine pharmacokinetics and their active intracellular anabolites, tenofovir-diphosphate and emtricitabine-triphosphate, in transwomen receiving feminizing hormones.