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Title
Drug-drug interactions between the use of feminizing hormone therapy and pre-exposure prophylaxis among transgender women: The iFACT study
Presenter
Akarin Hiransuthikul
Authors
A. Hiransuthikul1, K. Himmad1, S. Kerr2,3, N. Thammajaruk2, T. Pankam1, R. Janamnuaysook1, S. Mills4, R. Vannakit5, P. Phanuphak1, N. Phanuphak1, iFACT study team
Institutions
1The Thai Red Cross AIDS Research Centre, Prevention, Bangkok, Thailand, 2HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 3Kirby Institute, University of New South Wales, Sydney, Australia, 4LINKAGES Thailand FHI 360, Bangkok, Thailand, 5Office of Public Health, United States Agency for International Development, Bangkok, Thailand

Background: 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.
Methods: 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).


iFACT study scheme
[iFACT study scheme]


Results: Median (IQR) age, BMI, and CrCl were 21.5 (21-26) years, 20.6 (19.0-22.4) kg/m2, and 0.86 (0.75-0.94) 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.


E2 pharmacokinetic parameterWeek 3 (FHT only)Week 5 (PrEP+FHT)GMR (95%CI)p-value
AUC0-24 (pg*h/mL)775.13 (26.2)782.84 (39.6)1.01 (0.89 - 1.15)0.88
Cmax (pg/mL)51.47 (26.9)55.76 (32.9)1.08 (0.94 - 1.24)0.25
C24 (pg/mL)15.15 (42.0)14.32 (67.4)0.95 (0.75 - 1.19)0.63
Half-life (h)11.25 (32.6)11.83 (50.9)1.05 (0.87 - 1.27)0.60
TFV pharmacokinetic parameterWeek 5 (PrEP+FHT)Week 8 (PrEP only)GMR (95%CI)p-value
AUC0-24 (mg*h/L)2.28 (26.2)2.63 (26.9)0.87 (0.78 - 0.96)0.009
Cmax (mg/L)0.36 (34.8)0.32 (25.3)1.10 (0.95 - 1.28)0.2
C24 (mg/L)0.04 (28.8)0.05 (28.0)0.83 (0.76 - 0.90)<0.001
Half-life (h)15.19 (15.4)15.69 (23.0)0.97 (0.88 - 1.07)0.53
[Summary of E2 and TFV pharmacokinetic parameters; data are presented in geometric mean (%CV)]


Conclusions: Our study demonstrated lower plasma TFV exposure in the presence of FHT, suggesting that FHT may potentially affect PrEP efficacy among TGW; but E2 exposure was not affected by PrEP. Further studies are warranted to determine whether these reductions in TFV are clinically significant.

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