Drug-Drug Interaction Study in Trans Women Living With HIV

NCT05663892 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: CTN 331
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Hiv; Transgenderism

Keywords

HIV; Feminizing Hormone Therapy; Transgender Women; Antiretroviral Therapy; Drug-Drug Interaction

Outcome Measures

Primary Outcomes (8)

• BIC, FTC, and TAF minimum plasma concentrations.

  Minimum plasma concentrations (Cmin) of BIC, FTC, and TAF concentrations will be compared between trans women living with HIV (group 1) and premenopausal cis women living with HIV (group 2).

  Month 2

• BIC, FTC, and TAF maximum plasma concentrations.

  Maximum plasma concentrations (Cmax) of BIC, FTC, and TAF concentrations will be compared between trans women living with HIV (group 1) and premenopausal cis women living with HIV (group 2).

  Month 2

• BIC, FTC, and TAF area under the curve (AUC) plasma concentrations.

  AUC plasma concentrations of BIC, FTC, and TAF will be compared between trans women living with HIV (group 1) and premenopausal cis women living with HIV (group 2).

  Month 2

• 2h PBMC and DBS TFV-DP and FTC-TP concentrations.

  PBMC and DBS TFV-DP and FTC-TP concentrations done at 2h after ingestion of medications will be compared between trans women living with HIV (group 1) and premenopausal cis women living with HIV (group 2).

  Month 2

• Minimum serum concentrations (Cmin) of estradiol.

  Estradiol Cmin at month 2 will be compared between groups 1 and 3.

  Month 2

• 4 hour serum concentration (C4h) of estradiol

  Estradiol C4h at month 2 and the proportions of the month 2 C4h that are within target (200 to 735 pmol/L) and will be compared between groups 1 and 3.

  Month 2

• Maximum serum concentrations (Cmax) of estradiol

  Estradiol Cmax at month 2 will be compared between groups 1 and 3.

  Month 2

• Estradiol serum concentration area under the curve (AUC)

  Estradiol AUC at month 2 will be compared between groups 1 and 3.

  Month 2

Secondary Outcomes (10)

• Baseline estradiol pre-dose serum concentration (Cmin) and comparison to month 2

  Months 0 & 2

• Baseline estradiol C4h serum concentration and comparison to month 2

  Months 0 & 2

• Baseline total testosterone serum concentration and comparison to month 2

  Months 0 & 2

• FEM-SQ questionnaire score

  Months 0, 2 & 6

• Proportion of patient with an undetectable HIV-RNA.

  Months 0, 2 & 6

Other Outcomes (5)

• Basic sociodemographic variables

  Month 0

• Clinical variables

  Months 0 & 2

• FHT regimens

  Month 0

Study Arms (3)

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

EXPERIMENTAL

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

Drug: Biktarvy 50/200/25 Tab; Drug: Estradiol Tablets

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

ACTIVE COMPARATOR

Cis women living with HIV, taking: -Biktarvy

Drug: Biktarvy 50/200/25 Tab

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

ACTIVE COMPARATOR

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

Drug: Estradiol Tablets

Interventions

Biktarvy 50/200/25 Tab 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 2) - Cis Women Living with HIV; Investigational Population (Group 1) - Trans women living with HIV

Estradiol Tablets 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.

Also known as: Oral 17(beta)-estradiol

Comparator Population (Group 3) - Trans Women Living without HIV; Investigational Population (Group 1) - Trans women living with HIV

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: This study is open to: * Transgender women or persons with transfeminine experience, taking feminizing hormone therapy (oral estradiol) * Cisgender women.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• Is 18 years of age or older;
• Is living with HIV;
• Is currently taking combination ART and has been taking these medications for at least 3 months prior to the screening visit;
• 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;
• 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;
• Is willing to switch to or stay on B/F/TAF for the duration of the study (i.e., 6 months);
• 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:
• 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;
• 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;
• 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;
• Is willing to keep their anti-androgen (if applicable) medication(s) unchanged until the completion of the Month2 visit;
• 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;
• Is willing and able to provide full consent for their participation.

You may not qualify if:

• Is clinically unable to switch ART to B/F/TAF based on their physician's opinion;
• Is taking hormonal non-prescription or natural health products in addition to feminizing hormone therapy;
• Has significant underlying diseases which could worsen due to their participation, or affect their ability to follow the study procedures;
• Has kidney or liver impairment (ALT \> 5X normal; serum creatinine \[eGFR\] \< 30 mL per minute);
• 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).
• Has a known hypersensitivity to bictegravir (BIC), emtricitabine (FTC), tenofovir alafenamide (TAF) or to any ingredient in the formulation.
• Is a cis woman (individual assigned female sex at birth who currently identifies as a woman);
• Is of reproductive age and 18 years of age or older;
• Is living with HIV;
• 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);
• Is currently taking combination ART and has been taking these medications for at least 3 months prior to screening;
• 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;
• 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;
• Is willing to switch to or stay on B/F/TAF for the duration of the study (i.e., 6 months);
• Is willing and able to provide full consent for their participation.

Sponsors & Collaborators

• Maple Leaf Research: lead

Study Sites (1)

Maple Leaf Research

Toronto, Ontario, M5G1K2, Canada

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Transsexualism

Interventions

Estradiol

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Sexuality; Sexual Behavior; Behavior

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Mona Loutfy, MD, MPH

  Maple Leaf Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: November 27, 2022
• First Posted: December 23, 2022
• Study Start: November 23, 2022
• Primary Completion: November 1, 2024
• Study Completion: January 1, 2025
• Last Updated: September 26, 2024

Record last verified: 2024-09

Locations

CA (1)