Estradiol Therapy for HIV in Transgender Women

(GET IT RIgHT Trial)

No longer recruiting at 28 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of HIV treatments alongside estradiol therapy for transgender women living with HIV. Researchers aim to determine if hormone therapy impacts the effectiveness of HIV medications. Participants will receive estradiol (a type of estrogen) for 48 weeks while continuing their HIV treatment. This trial targets transgender women who have been on HIV medication for at least 24 weeks and wish to start or resume hormone therapy. As a Phase 2 trial, it measures how well the treatment works in an initial, smaller group of people.

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.

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

Research has shown that estradiol, a hormone used in feminizing therapy, is generally safe for transgender women, including those with HIV. Studies have found that estradiol in hormone therapy can improve adherence to HIV medication.

While taking estradiol, some individuals might experience mild side effects like mood changes or headaches. The HIV medications studied—bictegravir, dolutegravir, and darunavir—are also known to be safe and are commonly prescribed to people with HIV.

Overall, evidence suggests that both estradiol and the HIV medications in this trial are safe. However, individuals should consult a doctor if they have any concerns or questions about treatments. Doctors can provide more information based on specific health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using estradiol therapy for HIV in transgender women because it explores how hormone therapy might interact with HIV treatments. Unlike standard HIV treatments that focus solely on suppressing the virus, estradiol therapy could offer additional benefits by aligning with the gender-affirming needs of transgender women. This approach is unique because it investigates whether hormone therapy could have positive effects on health outcomes and quality of life for transgender women living with HIV. By integrating gender-affirming care into HIV treatment, researchers are hopeful for more holistic health improvements in this population.

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

This trial will evaluate the effects of estradiol therapy in transgender women with HIV. Studies have shown that transgender women taking estrogen achieve better results in their HIV care compared to those not taking estrogen. Research indicates that estradiol, a form of estrogen, does not significantly alter HIV medication levels in the body, so it should not interfere with HIV treatment. However, some HIV medications can reduce feminizing hormone levels by about 36%, potentially affecting the effectiveness of hormone therapy. Despite this, access to hormone therapy has been linked to better adherence to HIV treatment, meaning individuals are more likely to consistently take their medication. Participants in this trial will be divided into groups based on their HIV treatment regimen, including BIC-treated, DTG-treated, and boosted DRV-treated groups. ^{1 2 3 5 6}

Who Is on the Research Team?

Jordan E. Lake, MD, MSc

Principal Investigator

Houston AIDS Research Team CRS

Kimberly K. Scarsi, PharmD, MS, FCCP

Principal Investigator

University of Nebraska

Jorge A. Gallardo-Cartagena, MD

Principal Investigator

Barranco CRS

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a study of 1495 trans women, only 71.8% of those with HIV were prescribed feminizing hormone therapy (FHT), compared to 88.4% of those without HIV, indicating a potential gap in treatment for trans women living with HIV.

Despite concerns about drug-drug interactions, serum estradiol and testosterone levels were similar among trans women on FHT regardless of their HIV status, suggesting that FHT can be safely administered alongside antiretroviral therapy (ART).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feminizing hormone therapy in a Canadian cohort of transgender women with and without HIV. Armstrong, I., Lacombe-Duncan, A., Shokoohi, M., et al.[2023]

In a survey of 87 transgender women in Los Angeles, 54% were living with HIV and 64% were using hormone therapy, highlighting the significant overlap between these two treatments.

Concerns about drug-drug interactions between hormone therapy and antiretroviral therapy led to 40% of participants not adhering to their prescribed treatments, indicating a critical need for better communication and integration of care between providers.

NCBI (Pubmed)

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. Braun, HM., Candelario, J., Hanlon, CL., et al.[2020]

Interviews with 9 HIV-positive trans women and 15 HIV providers in Manila revealed that provider communication styles significantly impact the integration of feminizing hormone therapy (FHT) and antiretroviral therapy (ART), with non-affirmative rhetoric potentially hindering treatment decisions.

The study highlights the need for a gender-affirmative HIV care framework, as misalignment between provider concerns and patient goals can lead to mixed regimens and beliefs about FHT and ART among trans women, emphasizing the importance of training providers in gender-affirmative practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gender affirmative HIV care framework: Decisions on feminizing hormone therapy (FHT) and antiretroviral therapy (ART) among transgender women. Restar, AJ., Santamaria, EK., Adia, A., et al.[2023]

Transgender women (TGW) face significant barriers to effective HIV treatment, leading to lower rates of virologic suppression and higher mortality, with an HIV prevalence of 19.1% among TGW worldwide.

There is a lack of comprehensive studies on drug-drug interactions (DDIs) between feminizing hormone regimens and antiretroviral therapy (ART), particularly concerning the effects of different types and doses of estrogens, highlighting the need for further research to ensure safe and effective treatment for HIV-positive TGW.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices. Radix, A., Sevelius, J., Deutsch, MB.[2022]

Hormonal therapy for male to female transgender patients aims to maintain estrogen levels within a normal physiological range, which is crucial for managing gender dysphoria.

In three cases of transgender HIV-positive women, the antiretroviral drug efavirenz was found to significantly affect the metabolism of estradiol, potentially impacting the effectiveness of hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Efavirenz on Estradiol Metabolism in Transgender Women. Leinung, MC., Miller, CH., Tehrani, B., et al.[2020]

In a study of 15 HIV-negative transwomen taking PrEP, plasma levels of tenofovir and emtricitabine were found to be lower compared to historical data from cisgender adults, which may affect the effectiveness of PrEP in this population.

Despite lower plasma concentrations, the active forms of the drugs, tenofovir-diphosphate and emtricitabine-triphosphate, were found to be higher in transwomen's cells than previously reported, suggesting that intracellular drug levels may still provide protective effects against HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma and intracellular pharmacokinetics of tenofovir disoproxil fumarate and emtricitabine in transgender women receiving feminizing hormone therapy. Cirrincione, LR., Podany, AT., Havens, JP., 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 a study of 20 transgender women with newly diagnosed HIV, the pharmacokinetics of estradiol (E2) were significantly reduced when combined with antiretroviral therapy (ART), indicating potential drug-drug interactions that could affect hormone therapy effectiveness.

Some pharmacokinetic parameters of tenofovir (TFV) and efavirenz (EFV) were also lower when feminizing hormone therapy (FHT) was present, suggesting that both therapies may influence each other's effectiveness, warranting further investigation into their clinical significance.

NCBI (Pubmed)

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. Hiransuthikul, A., Himmad, L., Kerr, SJ., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4949308/

Transgender women, hormonal therapy and HIV treatment Studies have shown that transgender women (TGW) are disproportionately affected by HIV, with an estimated HIV prevalence of 19.1% among TGW ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9577885/

The role of gender-affirming hormonal care in HIV ... Compared with cis-SMM, trans-women who were prescribed estrogen had better HIV care continuum outcomes; trans-women not prescribed estrogen had worse outcomes.

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

Feminizing hormones don't affect PrEP drug levels According to the study abstract, estradiol levels did not change significantly. Spironolactone levels decreased slightly but probably not enough ...

5. aidsmap.com aidsmap.com/news/feb-2020/hiv-drugs-reduce-feminising-hormone-levels-36-hiv-positive-trans-women-thai-study

HIV drugs reduce feminising hormone levels by 36% in ... Transgender people. HIV drugs reduce feminising hormone levels by 36% in HIV-positive trans women, Thai study finds. Primary tabs. View(active ...

6. cdc.gov cdc.gov/mmwr/volumes/73/su/su7301a4.htm

Nonprescription Hormone Use Among Transgender Women Findings suggest that transgender women were more likely to use GAHT without a prescription in situations of economic and social marginalization.