Tenofovir Disoproxil Fumarate / Emtricitabine versus Estradiol Valerate plus Cyproterone Acetate
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Study Design
Concerns about potential drug-drug interactions (DDI)
between feminizing hormone therapy (FHT) and pre-exposure prophylaxis
(PrEP) have hampered uptake and adherence of PrEP among
transgender women (TGW). To determine DDI between FHT and
PrEP, we measured pharmacokinetic parameters of blood plasma tenofovir
(TFV), estradiol (E2), and testosterone.
Study Results
Twenty TGW who never underwent orchiectomy and had
not received injectable FHT within 6 months were enrolled between
January and March 2018. FHT (estradiol valerate 2 mg and cyproterone
acetate 25 mg) were prescribed to participants at baseline
until week 5, and week 8 until the end of study. PrEP (tenofovir disoproxil
fumarate 300 mg/emtricitabine 200 mg) was initiated at week 3
and continued without interruption. Intensive E2 pharmacokinetic
parameters and trough serum testosterone concentration (Ctrough)
were measured at weeks 3 and 5 (assessing DDI between PrEP and
FHT), and intensive TFV pharmacokinetic parameters were measured
at weeks 5 and 8 (assessing DDI between FHT and PrEP).
Study Conclusions
Median (IQR) age, BMI, and CrCl were 21.5 (21 to 26)
years, 20.6 (19.0 to 22.4) kg/m2, and 0.86 (0.75 to 0.94) mL/min,
respectively. The geometric mean (%CV) of area under curve from
time zero to 24 hr (AUC0-24), maximum concentration (Cmax), and concentration
at 24 hr (C24) of E2 at weeks 3 and 5 were 775.13 (26.2)
pg*h/mL, 51.47 (26.9) pg/mL, and 15.15 (42.0) pg/mL; and 782.84
(39.6), 55.76 (32.9), and 14.32 (67.4), respectively. The geometric
mean (%CV) of TFV AUC0-24, Cmax, and C24 at weeks 5 and 8 were
2.28 (26.2) mg*h/L, 0.36 (34.8) mg/L, and 0.04 (28.8) mg/L; and 2.63
(26.9), 0.32 (25.3), and 0.05 (28.0), respectively. The geometric mean
of AUC0-24 and C24 of TFV at week 5 were significantly less than that
at week 8 by 13% (p = 0.009) and 17% (p < 0.001), respectively.
There were no significant changes in E2 pharmacokinetic parameters
and median (IQR) Ctrough of bioavailable testosterone between week 3
and 5.
References
Hiransuthikul A, Himmad K, Kerr S, Thammajaruk N, Pankam T, Janamnuaysook R, Phanuphak N. Drug-drug interactions between the use of feminizing hormone therapy and pre-exposure prophylaxis among transgender women: the ifact study. International Aids Conference. Amsterdam, Netherlands. 22; July 2018.
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