Drug-Drug Interaction Study in Trans Women Living With HIV

NCT ID: NCT05663892

Last Updated: 2024-09-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-23
• Study Completion Date: 2025-01-31

Brief Summary

Introduction: Transgender (trans) women have been found to be at higher risk of and to be disproportionally affected by HIV. Trans women with HIV have also been found to have low usage and adherence rates to antiretroviral therapy (ART). Both healthcare providers and trans women, themselves, have expressed concerns of drug-drug interactions (DDIs) between ART drugs and feminizing hormones, which have in turn been shown to contribute to low rates of ART usage amongst trans women 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 (pharmaceutical and/or surgical and/or medical) on the antiretroviral combination bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and vice versa.

Methods and Analysis: Participants will be assigned to three groups: group 1 will include 15 trans women with HIV who are taking feminizing hormones and ART (investigational group); group 2 will include 15 premenopausal cis women with HIV taking ART (ART control group); group 3 will include 15 trans women without HIV taking feminizing hormones (hormone control group). Women with HIV will have to be virally suppressed for at least three months and they will have to already be taking B/F/TAF or have their current ART regimen switched to B/F/TAF at baseline. Trans women participants will be required to be on 2 mg oral estradiol or higher and an anti-androgen (pharmaceutical, medical or surgical). Plasma ART drug concentrations will be sampled at the 2-month visit and compared among trans women with HIV on feminizing hormones and premenopausal cis women with HIV. Serum estradiol and total testosterone concentrations will be sampled at the baseline and month 2 visits and compared among trans women with and without HIV. If successful, this trial will serve to provide empirical evidence regarding a lack of, or presence of DDIs between B/F/TAF and feminizing hormones.

Dissemination: The findings will be disseminated through publication in peer-reviewed journals as well as presented at national and international conferences and community groups.

Detailed Description

Introduction: Transgender (trans) women have been found to be at higher risk of and to be disproportionally affected by HIV for multiple biologic and social reasons. Trans women living with HIV have also been found to have low usage and adherence rates to antiretroviral therapy (ART). Both healthcare providers and trans women, themselves, have expressed concerns of drug-drug interactions (DDIs) between ART drugs and feminizing hormones, which have in turn been shown to contribute to low rates of ART usage amongst 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 (pharmaceutical and/or surgical and/or medical)) on the antiretroviral combination bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and vice versa.

Methods and analysis: Participants will be assigned to three groups: group 1 will include 15 trans women living with HIV who are taking feminizing hormones and ART (investigational group); group 2 will include 15 premenopausal cis women living with HIV taking ART (ART control group); group 3 will include 15 trans women living without HIV taking feminizing hormones (hormone control group). Women living with HIV will have to be virally suppressed for at least three months and they will have to already be taking B/F/TAF or have their current ART regimen switched to B/F/TAF at baseline. Trans women participants will be required to be on 2 mg oral estradiol or higher and an anti-androgen (pharmaceutical, medical or surgical). Plasma ART drug concentrations will be sampled at the 2-month visit and compared among trans women living with HIV on feminizing hormones and premenopausal cis women living with HIV. Serum estradiol and total testosterone concentrations will be sampled at the baseline and month 2 visits and compared among trans women living with and without HIV. The primary endpoints are B/F/TAF pharmacokinetic parameters (Cmin, Cmax and AUC) between trans and cis women living with HIV at month 2 and the estradiol concentrations (Cmin, C4h, Cmax and AUC) and the proportions of the month 2 C4h that are within target (200 to 735 pmol/L) between trans women living with and without HIV at month 2. Other endpoints will include the mean estradiol and testosterone concentrations at baseline and the difference between baseline and month 2 estradiol pre-dose and C4h, satisfaction with feminizing hormones, HIV viral load, adherence, adverse events, patient-reported outcomes (i.e., symptoms), satisfaction with ART regimen and health status. If successful, this trial will serve to provide empirical evidence regarding a lack of, or presence of DDIs between B/F/TAF and feminizing hormones.

Dissemination: The findings will be disseminated through publication in peer-reviewed journals as well as presented at national and international conferences and community groups.

Conditions

Hiv; Transgenderism

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Investigational Population (Group 1) - Trans women living with HIV

Trans women living with HIV, taking:

• Biktarvy
• Oral 17(Beta)-Estradiol

Group Type: EXPERIMENTAL

Biktarvy 50/200/25 Tab

Intervention Type: DRUG

As the HIV ART, the combination of B/F/TAF, known as Biktarvy®, which is a widely available Single Tablet Regimen (STR) approved by Health Canada is the drug under investigation. Participants in groups 1 and 2 will either have to already be taking B/F/TAF or will be required to switch to it at baseline and they will self-administer B/F/TAF once daily in the morning, with or without food. Participants taking their dosage at night will be required to switch to a morning dose at the screening visit.

Estradiol Tablets

Intervention Type: DRUG

Oral 17(beta)-estradiol as the estrogen and an anti-androgen (pharmaceutical [e.g., spironolactone, cyproterone, finasteride, leuprolide, bicalutamide, dutasteride] and/or surgical [orchiectomy] and/or medical [hypogonadism]).Doses of estradiol range from 1 mg to a maximum of 6 mg per day.

Participants must take 2 mg until the Month 2 Visit. Trans women participants in both groups 1 and 3 must divide their dose to twice a day (BID) if they are taking > 2 mg per day and take 2 mg in the morning and the rest of the dosing in the evening. Participants who are only taking 2mg of estradiol once daily at night must switch their dosing to the morning. Participants who either crush or take the oral estradiol sublingually must switch to swallowing the tablet orally from the day after the screening visit until the Month 2 visit, otherwise the estradiol concentrations will be markedly higher.

Comparator Population (Group 2) - Cis Women Living with HIV

Cis women living with HIV, taking:

-Biktarvy

Group Type: ACTIVE_COMPARATOR

Biktarvy 50/200/25 Tab

Intervention Type: DRUG

As the HIV ART, the combination of B/F/TAF, known as Biktarvy®, which is a widely available Single Tablet Regimen (STR) approved by Health Canada is the drug under investigation. Participants in groups 1 and 2 will either have to already be taking B/F/TAF or will be required to switch to it at baseline and they will self-administer B/F/TAF once daily in the morning, with or without food. Participants taking their dosage at night will be required to switch to a morning dose at the screening visit.

Comparator Population (Group 3) - Trans Women Living without HIV

Trans women living without HIV, taking:

-Oral 17(Beta)-Estradiol

Group Type: ACTIVE_COMPARATOR

Estradiol Tablets

Intervention Type: DRUG

Oral 17(beta)-estradiol as the estrogen and an anti-androgen (pharmaceutical [e.g., spironolactone, cyproterone, finasteride, leuprolide, bicalutamide, dutasteride] and/or surgical [orchiectomy] and/or medical [hypogonadism]).Doses of estradiol range from 1 mg to a maximum of 6 mg per day.

Participants must take 2 mg until the Month 2 Visit. Trans women participants in both groups 1 and 3 must divide their dose to twice a day (BID) if they are taking > 2 mg per day and take 2 mg in the morning and the rest of the dosing in the evening. Participants who are only taking 2mg of estradiol once daily at night must switch their dosing to the morning. Participants who either crush or take the oral estradiol sublingually must switch to swallowing the tablet orally from the day after the screening visit until the Month 2 visit, otherwise the estradiol concentrations will be markedly higher.

Interventions

Biktarvy 50/200/25 Tab

As the HIV ART, the combination of B/F/TAF, known as Biktarvy®, which is a widely available Single Tablet Regimen (STR) approved by Health Canada is the drug under investigation. Participants in groups 1 and 2 will either have to already be taking B/F/TAF or will be required to switch to it at baseline and they will self-administer B/F/TAF once daily in the morning, with or without food. Participants taking their dosage at night will be required to switch to a morning dose at the screening visit.

Intervention Type: DRUG

Estradiol Tablets

Oral 17(beta)-estradiol as the estrogen and an anti-androgen (pharmaceutical [e.g., spironolactone, cyproterone, finasteride, leuprolide, bicalutamide, dutasteride] and/or surgical [orchiectomy] and/or medical [hypogonadism]).Doses of estradiol range from 1 mg to a maximum of 6 mg per day.

Participants must take 2 mg until the Month 2 Visit. Trans women participants in both groups 1 and 3 must divide their dose to twice a day (BID) if they are taking > 2 mg per day and take 2 mg in the morning and the rest of the dosing in the evening. Participants who are only taking 2mg of estradiol once daily at night must switch their dosing to the morning. Participants who either crush or take the oral estradiol sublingually must switch to swallowing the tablet orally from the day after the screening visit until the Month 2 visit, otherwise the estradiol concentrations will be markedly higher.

Intervention Type: DRUG

Other Intervention Names

Oral 17(beta)-estradiol

Eligibility Criteria

Inclusion Criteria

1. Is a trans woman or person with transfeminine experience (individual assigned male sex at birth who currently identifies as a woman or person with transfeminine experience and is at any stage of medical, social, or legal transition);

2. Is 18 years of age or older;

3. Is living with HIV;

4. Is currently taking combination ART and has been taking these medications for at least 3 months prior to the screening visit;

5. Is willing to adjust their ART dosing to the morning if they are currently taking it at night for at least 28 days before the baseline visit until the completion of the Month 2 visit;

6. Has had an undetectable viral load for at least 3 months on at least two occasions, where most recent (within 12 months including screening) VL<40 copies/mL and second (within 24 months) VL<200 copies/mL with no suggestion of relevant ART drug resistance prior to screening;

7. Is willing to switch to or stay on B/F/TAF for the duration of the study (i.e., 6 months);

8. Is currently taking oral estradiol (2 mg or higher) and an anti-androgen (pharmaceutical [e.g., spironolactone, cyproterone, finasteride, leuprolide, bicalutamide, dutasteride] and/or surgical [orchiectomy] and/or medical [hypogonadism]) and has been taking these medications together at the current dose for at least 3 months prior to the screening visit; AND:

1. Is willing to adjust their oral estradiol dosing to twice a day if they are taking > 2 mg per day (which is currently recommended as best practice) for at least 28 days before the baseline visit until the completion of the Month 2 visit, with the morning dose set at 2 mg (remaining dose can be taken at night), OR;

2. If their estradiol dosing is 2 mg per day and they are currently taking their estradiol at night, they must be willing to switch their dosing to the morning for at least 28 days before the baseline visit until the completion of the Month 2 visit;

3. Is willing to swallow their oral estradiol if they are currently taking it sublingually or crushing it for at least 28 days before the baseline visit and until the completion of the Month 2 visit;

4. Is willing to keep their anti-androgen (if applicable) medication(s) unchanged until the completion of the Month2 visit;

9. If taking progesterone, is willing to keep the same medication/dose until the completion of the Month 2 visit and must have been taking that dose for at least 3 months prior to the screening visit;

10. Is willing and able to provide full consent for their participation.

1. Is a cis woman (individual assigned female sex at birth who currently identifies as a woman);

2. Is of reproductive age and 18 years of age or older;

3. Is living with HIV;

4. Has a regular period (every 24 - 35 days), or if period is irregular or absent, it is due to the administration of a progesterone only hormone contraceptive (see Appendix B1); or if uterus removed (hysterectomy), ovarie(s) remain functional (FSH level<27.0 IU/L);

5. Is currently taking combination ART and has been taking these medications for at least 3 months prior to screening;

6. Is willing to adjust their ART dosing to the morning if they are currently taking it at night for at least 28 days before the baseline visit until the completion of the Month 2 visit;

7. Has had an undetectable viral load for at least 3 months on at least two occasions, where most recent (within 12 months including screening) VL<40 copies/mL and second (within 24 months) VL<200 copies/mL with no suggestion of relevant ART drug resistance prior to screening;

8. Is willing to switch to or stay on B/F/TAF for the duration of the study (i.e., 6 months);

9. Is willing and able to provide full consent for their participation.

1. Is a trans woman or person with transfeminine experience (defined as individual assigned male sex at birth who currently identifies as a woman or person with transfeminine experience irrespective of medical, social, or legal transition);

2. Is 18 years of age or older;

3. Is HIV negative at screening;

4. Is currently taking oral estradiol (2mg or higher) and an anti-androgen (pharmaceutical [i.e., spironolactone, cyproterone, finasteride, leuprolide, bicalutamide, dutasteride] and/or surgical [orchiectomy] and/or medical [hypogonadism]) and has been taking these medications at the current dose for at least 3 months prior to the screening visit, AND:

1. Is willing to adjust their oral estradiol dosing to twice a day if they are taking > 2 mg per day (which is currently recommended as best practice) for at least 28 days before the baseline visit until the completion of the Month 2 visit, with the morning dose set at 2 mg (remaining dose can be taken at night) OR;

2. If their estradiol dosing is 2 mg per day and they are currently taking their estradiol at night, they must be willing to switch their dosing to the morning for at least 28 days before the baseline visit until the completion of the Month 2 visit;

3. Is willing to swallow their oral estradiol if they are currently taking it sublingually or crushing it for at least 28 days before the baseline visit until the completion of the Month 2 visit;

4. Is willing to keep their anti-androgen (if applicable) medication(s) unchanged until the completion of the Month2 visit;

5. If taking progesterone, is willing to keep their dose the same until the Month 2 visit and must have been taking that dose for at least 3 months prior to the screening visit;

6. Is willing and able to provide full consent for their participation.

Exclusion Criteria

1. Is clinically unable to switch ART to B/F/TAF based on their physician's opinion;

2. Is taking hormonal non-prescription or natural health products in addition to feminizing hormone therapy;

3. Has significant underlying diseases which could worsen due to their participation, or affect their ability to follow the study procedures;

4. Has kidney or liver impairment (ALT > 5X normal; serum creatinine [eGFR] < 30 mL per minute);

5. Is taking medications known to interact with feminizing hormones, B/F/TAF, or its individual components or has taken such medications within the past 28 days prior to baseline (List of prohibited medications in Appendix B1).

6. Has a known hypersensitivity to bictegravir (BIC), emtricitabine (FTC), tenofovir alafenamide (TAF) or to any ingredient in the formulation.

1. Is clinically unable to switch B/F/TAF based on their physician's opinion;

2. Is pregnant or is planning on getting pregnant for the duration of the study;

3. Has undergone surgery to remove their ovaries (i.e. oophorectomy) or has a condition in which their ovaries produce little or no estrogen (i.e. primary ovarian insufficiency, hypogonadism) or does not have ovaries naturally (i.e. unilateral ovarian absence); total hysterectomy is allowed as long as ovaries are intact and functional;

4. Is taking an estrogen containing or conjugated estrogens hormonal therapies; IUD and progesterone only contraception are allowed (See Appendix B1/2 for list for both prohibited and allowed contraceptives);

5. Has significant underlying diseases which could worsen due to their participation, or affect their ability to follow the study procedures;

6. Has kidney or liver impairment (ALT > 5X normal; serum creatinine [eGFR] < 30 mL per minute);

7. Has a known hypersensitivity to bictegravir (BIC), emtricitabine (FTC), tenofovir alafenamide (TAF) or to any ingredient in the formulation.

8. Is taking medications known to interact with B/F/TAF, or its individual components or has taken such medications within the past 28 days prior to baseline (List of prohibited medications in Appendix B1/2).

1. Is taking hormonal non-prescription or natural health products in addition to feminizing hormone therapy;

2. Has taken HIV pre-exposure prophylaxis (PrEP) (i.e, TDF/FTC or TAF/FTC) or HIV post-exposure prophylaxis (PEP) in the prior 28 days from baseline and plans to continue during the study;

3. Has significant underlying diseases which could worsen due to their participation, or affect their ability to follow the study procedures;

4. Has kidney or liver impairment (ALT > 5X normal; serum creatinine [eGFR] < 30 mL per minute);

5. Is taking medications known to interact with feminizing hormones or has taken such medications within the past 28 days prior to baseline (List of prohibited medications in Appendix B1).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maple Leaf Research

OTHER

Sponsor Role: lead

Responsible Party

Mona Loutfy

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mona Loutfy, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Maple Leaf Research

Locations

Maple Leaf Research

Toronto, Ontario, Canada

Countries

Canada

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

CTN 331

Identifier Type: -

Identifier Source: org_study_id