About The Study

CTN 331 will use community-based research principles to investigate the pharmacokinetic effects of common feminizing hormone regimens (oral estradiol and an anti-androgen) on the antiretroviral therapy (ART) combination bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and vice versa. The ultimate goal is to determine if there are any drug–drug interactions between these therapeutic regimens. The CTN 331 researchers chose to investigate B/F/TAF specifically, as they believe it represents a safe, convenient, and highly effective strategy for trans women with HIV. Participants will be recruited from sites in Toronto and Montreal.

Background

Transgender (trans) women are disproportionately affected by HIV. A study of trans people living in Ontario estimated that HIV was ten times more prevalent among this population (2.9 per cent) than the overall provincial prevalence (0.23 per cent). Despite this, ART uptake and adherence are lower among trans people compared with cisgender people. A main reason for this is concern about drug–drug interactions between ART and feminizing hormones; a concern not only among trans women, but also some health care providers, who are hesitant to prescribe feminizing hormones to trans women on ART. As such, more research is needed on the concomitant use of ART and feminizing hormones to support an evidence-based approach for the management of trans women living with HIV.

Study Approach

Participants will be assigned to three groups: group one will include 15 trans women living with HIV who are taking feminizing hormones and ART (investigational group); group two will include 15 premenopausal cis women living with HIV taking ART (ART control group); and group three will include 15 trans women without HIV who are taking hormones (hormone control group). Each participant will attend a baseline visit and a follow-up visit at two months, where they will complete questionnaires and provide bloodwork.

Serum estradiol and total testosterone concentrations will be sampled at the baseline and month two visits and compared among trans women living with and without HIV, as well as to cis women. In addition, at the month two visit, plasma ART drug concentrations will be sampled and compared among trans women on feminizing hormones and premenopausal cis women who are not taking hormone therapy. The data gathered will indicate whether there are any drug–drug interactions between the estradiol-based feminizing hormone therapy and B/F/TAF ART regimen.

Eligibility Requirements

Required

Group one (investigational group)
  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 on combination ART for at least three months with an undetectable viral load on at least two occasions (one within 6 months and other within two years) with no suggestion of relevant ART drug resistance prior to screening;
    1. If they are currently taking their ART at night, they must be willing to switch their dosing to the morning (a physician will provide instructions on how to do this);
  5. Is willing to switch to B/F/TAF if not already on this combination ART regimen;
  6. Is on the feminizing hormone regimen of oral estradiol and an anti-androgen (e.g., spironolactone, cyproterone, finasteride, leuprolide, bicalutamide, dutasteride, and/or orchiectomy) for at least three months prior to initiation without dose adjustment, and:
    1. If their estradiol dosing is more than 2 mg per day, they must be willing to divide their dose to twice a day, or;
    2. If their estradiol dosing is less than 2 mg per day and they are currently taking their estradiol at night, they must be willing to switch their dosing to the morning (variable dosing of estradiol is acceptable in this study as it is the standard of care to titrate to reach the desired target concentration of estradiol);
  7. Is willing to keep their oral estradiol, anti-androgen, and ART medications at their study-required doses for the duration of the pilot study (i.e., for at least 28 days before next study visit);
  8. Is willing and able to provide full consent for their participation.
Group two (ART control group)
  1. Is a cis woman (individual assigned female sex at birth who currently identifies as a woman);
  2. Is 18 years of age or older;
  3. Is living with HIV;
  4. Is premenopausal by history (i.e. has no evidence of perimenopause with duration between menses of > three months in the past year);
  5. Is on combination ART for at least three months with an undetectable viral load on at least two occasions (one within 6 months and other within two years) with no suggestion of relevant ART drug resistance prior to screening;
    1. If they are currently taking their ART at night, they must be willing to switch their dosing to the morning (a physician will provide instructions on how to do this);
  6. Is willing to switch to B/F/TAF if not already on this combination ART regimen;
  7. Is willing to keep their ART medications at the study-required doses for the duration of the study;
  8. Is willing and able to provide full consent for their participation.
Group three (hormone control group)
  1. Is a trans woman (individual assigned male sex at birth who currently identifies as a woman and is at any stage of medical, social, or legal transition);
  2. Is 18 years of age or older;
  3. Says they are HIV negative prior to screening and are willing to have an HIV test at their screening/consent visit (and the result returns as negative);
  4. Is currently taking oral estradiol and an anti-androgen (i.e., spironolactone, cyproterone, finasteride, leuprolide, bicalutamide, dutasteride, and/or orchiectomy), and have been taking these medications at the current dose for at least 3 months prior to starting this study, AND:
    1. If their estradiol dosing is more than 2 mg per day, they must be willing to divide their dose to twice a day, or;
    2. If their estradiol dosing is less than 2 mg per day and they are taking their estradiol at night, they must be willing to switch their dosing to the morning (variable dosing of estradiol is acceptable in this study as it is the standard of care to titrate to reach the desired target concentration of estradiol);
  5. Is willing to keep their oral estradiol and anti-androgen medications at their study-required doses for the duration of the pilot study;
  6. Is willing and able to provide full consent for their participation.

Not Allowed

Group one (investigational group)
  1. Is clinically unable to switch ART based on their physician opinion;
  2. Is taking hormonal non-prescription or natural health products in addition to feminizing hormone therapy (i.e., oral estradiol and anti-androgen medications);
  3. Is taking their estradiol sublingually or crushing it and not willing to take it orally for the duration of the study;
  4. Has significant underlying diseases which could contribute to worsening of disease state or difficulty complying to therapy;
  5. Has hepatic or renal impairment (liver enzymes more than five times normal; estimated creatinine clearance less than 30 mL per minute);
  6. Is taking medications known to interact with feminizing hormones, B/F/TAF, or its individual components or has taken such medications within the past 30 days, including Tamoxifen.
Group two (ART control group)
  1. Is clinically unable to switch ART based on their physician opinion;
  2. Is planning on getting pregnant in the next year;
  3. Is taking hormonal therapy, such as hormonal contraception (intrauterine devices are allowed);
  4. Has significant underlying diseases which could contribute to worsening of disease state or difficulty complying to therapy;
  5. Has hepatic or renal impairment (liver enzymes more than five times normal; estimated creatinine clearance < 30 mL per minute);
  6. Is taking medications known to interact with B/F/TAF, or its individual components or has taken such medications within the past 30 days.
Group three (hormone control group)
  1. Is taking hormonal non-prescription or natural health products in addition to feminizing hormone therapy;
  2. Is taking their estradiol sublingually or crushing it and is not willing to take it orally for the duration of the study;
  3. Is taking HIV PrEP (i.e, TDF/FTC or TAF/FTC) or post-exposure prophylaxis (PEP) for the prevention of HIV;
  4. Has significant underlying diseases which could contribute to worsening of disease state or difficulty complying with study procedures;
  5. Is taking medications known to interact with feminizing hormones, including Tamoxifen.

Additional Information

In addition to the CTN Investigators listed below, other principal investigators of CTN 331 are Dr. Kim Scarsi, Dr. Alice Tseng, and Ms. Yasmeen Persad.

If you would like to take part in this study or want more information, please contact Roberta:
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416-454-9148

Principal Investigators

Here’s who is leading this study.

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Dr. Mona Loutfy

CTN Investigator

Women's College Research Institute; University of Toronto; Maple Leaf Medical Clinic

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Participating Sites

Here’s where this study is being conducted.

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