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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how transgender women with HIV respond to both feminizing hormones and the HIV medication Biktarvy. Researchers seek to determine if these medicines interact when taken together, potentially affecting the efficacy of the HIV treatment. The trial includes three groups: transgender women with HIV using both treatments, cisgender women with HIV using only Biktarvy, and transgender women without HIV using only feminizing hormones. This trial suits transgender women living with HIV who are already on both Biktarvy and feminizing hormones, with stable HIV control for at least three months. As a Phase 4 trial, this research focuses on understanding how the already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for Biktarvy and Estradiol Tablets?

Research has shown that both Biktarvy (a combination of three HIV medications) and estradiol (a hormone used for feminization) are generally safe when used separately. Biktarvy is approved for treating HIV and is widely used, with studies indicating a good safety record and few serious side effects.

Estradiol is commonly used as part of hormone therapy and is generally safe when monitored by healthcare providers. However, concerns exist about potential interactions between these two treatments, especially for trans women with HIV.

This trial aims to study these interactions. It is in Phase 4, indicating that the treatments are already considered safe individually, but it remains important to assess how they work together. This research is crucial to ensure that using Biktarvy and estradiol together remains safe and effective for trans women living with HIV. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining Estradiol with Biktarvy for trans women living with HIV because it offers a tailored approach that acknowledges both gender-affirming care and HIV treatment. Most HIV treatments focus solely on managing the virus, but this combination addresses hormone therapy needs alongside viral suppression. Biktarvy is already a well-regarded antiretroviral for its convenience as a single-tablet regimen, and adding Estradiol could enhance the quality of life by supporting gender-affirming hormone therapy without compromising HIV control. This integrated approach may improve adherence to treatment and overall health outcomes for trans women.

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

Research has shown that Biktarvy (B/F/TAF) is highly effective for people living with HIV. One study found that Biktarvy was effective for 84.8% of participants after a year, indicating sustained efficacy for most individuals. In this trial, trans women living with HIV will receive both Biktarvy and Estradiol as part of their treatment. Estradiol, a hormone used in gender-affirming therapy, does not appear to interact significantly with Biktarvy. A study found that estradiol levels in trans women with HIV were similar to those without HIV, suggesting minimal interaction. This indicates that taking estradiol and Biktarvy together is likely safe and effective for managing HIV while supporting hormone therapy. ^{1 3 6 7 8}

Who Is on the Research Team?

Mona Loutfy, MD, MPH

Principal Investigator

Maple Leaf Research

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11798408/

Protocol of a drug–drug interaction study between ... Women with HIV must be on or switch to B/F/TAF at baseline and be virally suppressed for ≥3 months. Trans women must be taking a stable regimen ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772707625000578

Effectiveness and safety of tenofovir alafenamide ... TAF/FTC/BIC showed low virological failure in newly diagnosed people with HIV. Estimated TAF/FTC/BIC durability was 84.8% at 12 months, 75.5% at 24 months.

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. askgileadmedical.com askgileadmedical.com/docs/biktarvy/biktarvy-bicstar-study

For HCP's | Biktarvy® (BIC/FTC/TAF) BICSTaR Study Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for the treatment of people living with HIV (PLWH): 12-month effectiveness, persistence, and safety in ...

5. gilead.com gilead.com/news/news-details/2018/gilead-presents-data-from-phase-3-study-evaluating-women-who-switched-to-biktarvy-bictegravir-emtricitabine-and-tenofovir-alafenamide-from-a-boosted-protease-inhibitor-based-regimen-or-boost

Gilead Presents Data From Phase 3 Study Evaluating ... “This study demonstrates that Biktarvy offers a safety and efficacy profile that may help to care for women living with HIV.” Additional clinical trials of ...

6. withpower.com withpower.com/trial/phase-4-hiv-10-2022-e4a35

Estradiol + Biktarvy for Trans Women Living with HIV This trial investigates whether common hormone treatments for transgender women interfere with a specific HIV medication. It focuses on transgender women ...

7. clinicaltrial.be clinicaltrial.be/en/details/178129?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

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

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38992893/

Protocol of a drug-drug interaction study between bictegravir ... Women with HIV must be on or switch to B/F/TAF at baseline and be virally suppressed for ≥3 months. Trans women must be taking a stable regimen of ≥2 mg daily ...