Emtricitabine/Tenofovir Disoproxil Fumarate + Estradiol plus Medroxyprogesterone plus Spironolactone (Feminizing Hormones) = Precautionary

Effect on Concentration

Emtricitabine/Tenofovir Disoproxil Fumarate
Decrease
Applies within class?
No
Estradiol plus Medroxyprogesterone plus Spironolactone (Feminizing Hormones)
Increase
Applies within class?
No

Pharmacologic Effects

Emtricitabine/Tenofovir Disoproxil Fumarate
Effect
N/A
Applies within class?
No
Estradiol plus Medroxyprogesterone plus Spironolactone (Feminizing Hormones)
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 16-Aug-2018

Summary

Sources

Tenofovir Disoproxil Fumarate / Emtricitabine versus Estradiol/Medroxyprogesterone/Spironolactone ^

Study Design

HIV-infected women on a Truvada® containing regimen with HIV<50 copies/mL and CrCl>60 mL/min enrolled (N = 4 TGW; N = 4 CGW) between 01/2017 and 01/2018. Serum and RT biopsies were collected at a single visit. FHT included oral or injectable E2, medroxyprogesterone, and spironolactone. Serum E2 was measured with validated immunoassay (lower limits of quantification; LLOQ = 20 pg/mL). RT was homogenized and TFVdp/FTCtp and dATP/dCTP were measured by LC-MS/MS (LLOQ = 0.1 and 0.05 ng/ mL, respectively). Values below limits of quantification (BLQ) were imputed at sample specific LLOQ (depending on biopsy size; 4/28 measures). All measures were BLQ for 1 TGW, and excluded from statistical analyses (Student’s t-test and Pearson correlation using SASv9.4). Median (range) summary data are reported.

Study Results

Age, BMI and CrCl were 42 (34, 46) versus 57 (55, 59) years; 30 (24, 42) versus 36 (27, 38) kg/m2; and 114 (100, 192) versus 108 (61, 138) mL/min for TGW versus CGW, respectively. E2 concentrations in TGW (252 (73, 490) pg/mL) were consistent with peak E2 in a typical periovulatory phase. TFVdp:dATP was 7-fold lower in TGW versus CGW (p = 0.006; Table 1). One TGW exhibited TFVdp:dATP below an EC90 target ratio of 0.29. FTCtp:dCTP did not differ between groups and was above an EC90 target ratio of 0.07 in all participants. A significant inverse association was observed for log10E2 and TFVdp:dATP (r = 0.77; p = 0.04).

Study Conclusions

This is the first description of TFVdp/FTCtp rectal concentrations in TGW on FHT. TFVdp relative to dATP was significantly lower in TGW and decreased with increasing E2. A cisgender male comparator will also be studied to confirm these findings. These data confirm in vitro findings and suggest that feminizing E2 may impact PrEP efficacy.

References

Cottrell ML, Prince HM, Maffuid K, Poliseno A, White N, Sykes C, Nelson JA, Kashuba A. Altered tdf/ftc pharmacology in a transgender female cohort: implications for prep. International Aids Society. Amsterdam, Netherlands. 22; July 2018.