evaluating drug interactions between doravirine with estradiol and spironolactone in healthy transgender women

Conditions: Transgender Health; Gender Dysphoria; Transgender Women; Human Immunodeficiency Virus

Summary: transgender women living with human immunodeficiency virus (hiv) may prioritize gender-affirming hormonal therapy over antiretroviral drug therapy. hormonal therapy typically consists of oral estradiol and spironolactone, which induce drug-metabolizing enzymes after prolonged administration. this study evaluates the bi-directional potential drug interaction between the antiretroviral drug, doravirine, when co-administered with estradiol and spironolactone.

this study will consist of healthy transgender women volunteers randomized to a 1:1 sequence ("e" or "f") there are three periods and in each period there are one of three treatments treatment a: single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate alone treatment b: single-dose estradiol and spironolactone co-administered with placebo treatment c: single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone the primary outcome measures are the drug concentrations the primary comparisons are geometric mean ratios of drugs with potential perpetrators of drug interactions using a crossover method

Eligibility criteria:
inclusion criteria: * healthy self-identified transgender women (male-to-female) between 18-45 years old at the time of screening * have not undergone an orchiectomy * receiving oral estradiol and spironolactone for \>/= 3 months prior to study entry with a self-reported adherence to prescribed doses of \>/= 90% * agree to abstain from alcohol consumption throughout the duration of the study * be willing to briefly interrupt hormonal therapy prior to and during the study * if on pre-exposure prophylaxis (prep) therapy containing tenofovir alafenamide or tenofovir disoproxil fumarate, willing to discontinue prep at least 2 weeks before study start and for the duration of the study * agree to use condoms for all sexual activity prior to the start and throughout the duration of the study * evidence of a personal signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study exclusion criteria: * presence of clinically significant acute or chronic disease, that in the investigator's opinion, would compromise the participant's safety during the study * use of injectable or transdermal estradiol * use of any other hormonal replacement therapy, wit h the exception of oral estradiol and spironolactone * current use of any antiretroviral drug. this will not be exclusionary if participants reported discontinuing within 30 days of screening * creatinine clearance \</= 60 ml/min, as estimated by the cockcroft-gault equation * known anaphylactic or severe systemic reactions to any components of doravirine, lamivudine, or tenofovir disoproxil fumarate * positive hiv, hepatitis b or hepatitis c virus at screening. evidence of prior hepatitis b infection and immunity is not exclusionary. positive hepatitis c antibody with negative viral load or documented antiviral hepatitis c treatment with one post treatment non-detectable hepatitis c viral load is not exclusionary * recent significant blood or plasma donation