Drug-Drug Interaction Study in Trans Women Living With HIV

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

Interventions

DRUG

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.

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.

Sponsors & Collaborators

• Maple Leaf Research

  lead OTHER

Principal Investigators

• Mona Loutfy, MD, MPH · Maple Leaf Research

Study Design

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-11-23

Primary Completion

2024-11-30

Completion

2025-01-31

FDA Drug

Yes

Countries

• Canada

Study Locations