Estradiol + Biktarvy for Trans Women Living with HIV

(T-DDI Trial)

Overseen By Roberta Halpenny, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Maple Leaf Research

Must be taking: Antiretrovirals, Estradiol, Anti-androgens

Must not be taking: Hormonal supplements, Interacting medications

Disqualifiers: Kidney, Liver impairment, Hypersensitivity, 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

Compensation: Varies

Number of Visits: 6

Duration: 2 months

45 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial investigates whether common hormone treatments for transgender women interfere with a specific HIV medication. It focuses on transgender women with HIV who are concerned about drug interactions. The study will measure drug and hormone levels in the blood to see if they affect each other.

Will I have to stop taking my current medications?

Participants must switch to or continue taking the specific ART regimen B/F/TAF and maintain their current feminizing hormone regimen. They cannot take medications known to interact with B/F/TAF or feminizing hormones, and must have stopped such medications at least 28 days before the trial starts.

What data supports the effectiveness of the drug combination of Estradiol and Biktarvy for trans women living with HIV?

The research highlights concerns about drug interactions between feminizing hormone therapy (like Estradiol) and antiretroviral therapy (like Biktarvy), which can affect treatment adherence and hormone levels. However, both therapies are considered essential for transgender women living with HIV, suggesting their combined use is important despite potential interaction challenges. ^{1 2 3 4 5}

Is it safe to use Estradiol with Biktarvy for trans women living with HIV?

Studies have looked at the interactions between feminizing hormone therapy (like Estradiol) and antiretroviral therapy (like Biktarvy) in transgender women with HIV. These studies focus on how the drugs affect each other in the body, which is important for safety, but specific safety outcomes are not detailed in the available research. ^{1 3 6 7 8}

How is the drug combination of Estradiol and Biktarvy unique for trans women with HIV?

This treatment is unique because it combines feminizing hormone therapy (estradiol) with antiretroviral therapy (Biktarvy) specifically for transgender women with HIV, addressing potential drug interactions that can affect hormone levels and HIV treatment effectiveness. ^{1 3 4 5 9}

Research Team

Mona Loutfy, MD, MPH

Principal Investigator

Maple Leaf Research

Eligibility Criteria

This trial is for trans women living with HIV who are on feminizing hormone therapy and antiretroviral therapy (ART). They must be virally suppressed, willing to adjust their medication schedules, and take a specific ART regimen (B/F/TAF) for the study duration. Participants need to be adults with no relevant ART drug resistance.

Inclusion Criteria

The study is looking for transgender women who are living with HIV.

You were assigned male at birth but currently identify as a woman or person undergoing a transition to become a woman.

You need to switch the timing of your medication from night to morning for at least 28 days before starting the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Baseline measurements of serum estradiol and total testosterone concentrations are taken, and ART regimen is confirmed or switched to B/F/TAF

0 weeks

1 visit (in-person)

Treatment

Participants receive their assigned treatment regimen, and plasma ART drug concentrations are sampled at the 2-month visit

2 months

2 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and satisfaction with ART and feminizing hormone regimens

4 months

3 visits (in-person)

Treatment Details

Interventions

• Biktarvy 50/200/25 Tab
• Estradiol Tablets

Trial Overview The study investigates how common feminizing hormones used by trans women interact with the HIV treatment B/F/TAF. It compares blood levels of these drugs in trans women taking both treatments against cisgender women on HIV treatment and trans women not infected by HIV.

Participant Groups

Group I: Investigational Population (Group 1) - Trans women living with HIV Experimental Treatment 2 Interventions

Trans women living with HIV, taking: * Biktarvy * Oral 17(Beta)-Estradiol

Group II: Comparator Population (Group 3) - Trans Women Living without HIV Active Control 1 Intervention

Trans women living without HIV, taking: -Oral 17(Beta)-Estradiol

Group III: Comparator Population (Group 2) - Cis Women Living with HIV Active Control 1 Intervention

Cis women living with HIV, taking: -Biktarvy

Who Is Running the Clinical Trial?

Maple Leaf Research

Lead Sponsor

Trials

5

Recruited

280+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Feminizing hormone therapy in a Canadian cohort of transgender women with and without HIV. [2023]

2. 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]

3. 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]

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

The Effect of Efavirenz on Estradiol Metabolism in Transgender Women. [2020]

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]

6. England pubmed.ncbi.nlm.nih.gov

Effects of HIV antiretrovirals on the pharmacokinetics of hormonal contraceptives. [2008]

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

A Randomized Clinical Trial of Transgender Women Switching to B/F/TAF: The (mo)BETTA Trial. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Drug-drug interactions between feminizing hormone therapy and pre-exposure prophylaxis among transgender women: the iFACT study. [2023]

9. 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]