PrEP: wie lange hält die Wirkung einer Tablette an?

Das ist wohl die grosse Frage. Denn selbst wenn wir herausfinden, dass eine tägliche Gabe einer PrEP vor HIV schützt, so wird sich die Frage stellen, ob denn vielleicht eine Tablette nicht auch für 3 Tage wirkt. Eine Tablette pro vergnügtes Wochenende, sozusagen. Natürlich haben wir keine Antwort auf diese Frage, aber Kathy Patterson hat mindestens eine sehr schöne PK-Analyse von Tenofovir im Gewebe präsentiert. Sowohl Tenofovir als auch FTC bleiben relativ lange im Gewebe, doch nicht gleich lange und nicht gleich in jedem Gewebe (Vaginal- Rektal-Mukosa).

Exposure of extracellular and intracellular tenofovir and emtricitabine in mucosal tissues after a single of fixed-dose TDF/FTC: implications for pre-exposure HIV prophylaxis (PrEP)

K. Patterson¹, H. Prince¹, E. Kraft¹, A. Jones¹, S. Paul¹, N. Shaheen¹, M. Spacek¹, P. Heidt¹, S. Reddy², J. Rooney², M. Cohen¹, A. Kashuba^1
1University of North Carolina at Chapel Hill, Chapel Hill, United States, ²Gilead Sciences, Foster City, United States

Background: Current oral PrEP trials use tenofovir DF (TDF) + emtricitabine (FTC) both of which require intracellular phosphorylation (TFV-DP, FTC-TP). As intermittent PrEP dosing strategies are being considered, single dose pharmacokinetics (PK) in vulnerable mucosa were evaluated.
Methods: Eight HIV negative men and 7 women received one dose of TDF/FTC. Blood plasma (BP), cells (PBMC), cervical (CT), vaginal (VT) and rectal (RT) biopsies were collected 1, 2, 5, 7, 10, and 14 days post-dose. LC/MS/MS sample analysis had an LLOQ of 0.1ng/mL (TFV, FTC) and 2-10 fmol (TFV-DP, FTC-TP). PK data were generated non-compartmentally, and penetration ratios (PR) calculated as tissue AUC_0-14d ÷ blood AUC_0-14d. Median (range) data are reported.
Results: Subjects were 23 (19-37) yrs and 23.7 (18.8-28.6) kg/m² : 11 were white. After one dose, TFV could be detected for 14d in BP, VT, & RT; 7d in CT. TFV-DP was detected in all matrices for 14d. FTC could be detected for 14d in BP & RT; 10d in VT and CT. FTC-TP could be detected for 10d in PBMCs, 2d in VT & RT, and 1d in CT.

[Table 1]
Conclusions: Following one TDF/FTC dose, TFV and FTC AUC were highest in RT and CT, respectively. Over 7d, all analytes were detected in all matrices. Measurable 14d BP TFV+FTC imply that plasma adherence monitoring is feasible in PrEP trials. Although tissue TFV-DP exposures were similar to PBMCs, FTC-TP exposures were low. Wide variability of drug exposures in tissues highlights the need for accurate PK information to inform clinical studies.

Links:

• Patterson et.al. – THBS0305
• Slides mit Audio
• Präsentation (.ppt)