Reverse Transcriptase

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Presentation transcript:

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

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

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# 02983110) participants. Funding Sources: UNC CFAR (P30 AI50410) and NC TraCS (UL1TR002489).