1. Reverse Transcriptase
Feminizing hormone therapy may reduce effectiveness of tenofovir based ARV
TDF Mechanism
With FHT
Background: E2  nucleotidases
 cell surface expression may  dATP
 intracellular expression may  TFVdp
Design: HIV infected patients on TDF/FTC with HIV viral load <50copies/ml
Samples: Blood and rectal tissue biopsies collected at a single visit
Measurement:
HPLC-MS/MS: TFV,FTC in plasma and TFVdp, FTCtp, dATP, dCTP in PBMCs and rectal tissue homogenate
EIA: steroid hormones in serum
ddPCR: HIV RNA/DNA in rectal tissue homogenate
TFV
TFV
TFVdp
TFVdp
Reverse Transcriptase
dATP
dATP
AMP
Demographics; Median (Min, Max)
CGW (N=4)
TGW (N=4)
CGM (N=2)*
Age, years
57 (55, 59)
42 (34, 46)
58, 59
p<0.05
BMI, kg/m2
36 (27, 38)
30 (24, 42)
23, 23
Creatinine clearance, mL/min
108 (61, 138)
114 (99, 191)
79, 75
Estradiol, pg/mL
13 (8, 17)
193 (30, 619)
22, 22
Progesterone, ng/mL
0.21 (0.17, 0.30)
0.50 (0.27, 0.72)
0.34, 0.14
Testosterone, ng/dL
33 (25, 53)
33 (12, 125)
257, 303

2. Pharmacology Differed in Rectal Tissue of TGW vs CGW and CGM
All Analytes1 Median (Min, Max)
TFVdp:dATP Median (Min, Max)
1BLQ values imputed at ½ the sample specific lower limit of quantification based on sample mass

3. Female sex hormones correlate with TFVdp:dATP but not HIV DNA and RNA
CGW
TGW
CGM
ρ= -0.83, p<0.001
Acknowledgements: Special thanks to our clinical trial (NCT# ) participants. Funding Sources: UNC CFAR (P30 AI50410) and NC TraCS (UL1TR002489).