Protocol of a drug-drug interaction study between bictegravir/emtricitabine/tenofovir alafenamide and feminizing hormones in trans women living with HIV

Br J Clin Pharmacol. 2024 Oct;90(10):2349-2359. doi: 10.1111/bcp.16162. Epub 2024 Jul 11.

Abstract

Aims: Trans/transfeminine women are disproportionally affected by HIV. Concerns regarding negative drug-drug interactions (DDIs) between ART drugs and gender-affirming hormone therapy (GAHT), specifically feminizing hormone therapy (FHT), may contribute to the lower ART uptake by trans women with HIV compared with their cis counterparts. The aim of this study is to investigate the bidirectional pharmacokinetic effects of components of FHT regimens (oral oestradiol and androgen-suppressing medications) with the ART regimen (bictegravir/emtricitabine/tenofovir alafenamide [B/F/TAF)].

Methods: We present a protocol for a three-armed, parallel-group, longitudinal (6-month), DDI study. Group 1 includes 15 3trans women with HIV taking FHT and ART; group 2 includes 15 premenopausal cis women with HIV taking ART; group 3 includes 15 trans women without HIV taking FHT. 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 oral oestradiol and an anti-androgen (pharmaceutical, and/or surgical, and/or medical) for ≥3 months. Plasma ART drug concentrations will be sampled at Month 2 and compared between groups 1 and 2. Serum oestradiol concentrations will be sampled at baseline and Month 2 visits and compared between groups 1 and 3. The primary outcomes are B/F/TAF pharmacokinetic parameters (Cmin, Cmax and AUC) and oestradiol concentrations (Cmin, C4h, Cmax and AUC) at month 2.

Discussion: This study is of global importance as it provides critical information regarding safe coadministration of B/F/TAF and FHT, both of which are life-saving therapies for trans women with HIV.

Keywords: HIV; anti‐agents; drug interactions; feminizing hormones; transgender women.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adenine* / administration & dosage
  • Adenine* / analogs & derivatives
  • Adenine* / pharmacokinetics
  • Adult
  • Alanine / administration & dosage
  • Alanine / pharmacokinetics
  • Amides / administration & dosage
  • Amides / pharmacokinetics
  • Androgen Antagonists / administration & dosage
  • Androgen Antagonists / pharmacokinetics
  • Anti-HIV Agents* / administration & dosage
  • Anti-HIV Agents* / pharmacokinetics
  • Drug Combinations
  • Drug Interactions*
  • Emtricitabine* / administration & dosage
  • Emtricitabine* / pharmacokinetics
  • Estradiol* / administration & dosage
  • Estradiol* / blood
  • Estradiol* / pharmacokinetics
  • Female
  • HIV Infections* / drug therapy
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / pharmacokinetics
  • Heterocyclic Compounds, 4 or More Rings / administration & dosage
  • Heterocyclic Compounds, 4 or More Rings / pharmacokinetics
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Piperazines* / administration & dosage
  • Piperazines* / pharmacokinetics
  • Pyridones / administration & dosage
  • Pyridones / pharmacokinetics
  • Tenofovir* / administration & dosage
  • Tenofovir* / analogs & derivatives
  • Tenofovir* / pharmacokinetics
  • Transgender Persons*
  • Young Adult

Substances

  • Emtricitabine
  • Tenofovir
  • Anti-HIV Agents
  • Estradiol
  • Piperazines
  • Adenine
  • Heterocyclic Compounds, 4 or More Rings
  • Alanine
  • Pyridones
  • Drug Combinations
  • Androgen Antagonists
  • bictegravir
  • Heterocyclic Compounds, 3-Ring
  • bictegravir, emtricitabine, tenofovir alafenamide, drug combination
  • tenofovir alafenamide
  • Amides