Elodie Valade(1)(2), Saïk Urien(1)(2), Silvia Martinez Illamola(1)(3), Maïlys De Sousa Mendes(1)(2), Naïm Bouazza(1)(2), Frantz Foissac(1)(2), Déborah Hirt(1)(2)(3), Jean-Marc Tréluyer(1)(2)(3)
(1)Université Paris Descartes, Sorbonne Paris Cité, EA 08, (2)Unité de Recherche Clinique Paris Centre, AP-HP, Paris, France, (3)Service de Pharmacologie Clinique, AP-HP, Groupe Hospitalier Paris Centre, Paris, France
Objectives: The aims of this study were to describe the plasma and seminal plasma (SP) pharmacokinetics (PK) of emtricitabine (FTC) and tenofovir (TFV) in HIV-1-infected men, to assess the penetration of these drugs in the male genital tract and to evaluate their impact on the detectability of seminal plasma HIV load.
Methods: HIV-positive men from the EVARIST study (ANRS EP49) with undetectable plasma viral load for at least 6 months and receiving antiretroviral therapy with FTC and/or TFV were included. FTC and TFV plasma and SP concentrations were measured by LC-MS/MS. Data were analyzed using MONOLIX software version 4.1.4. Link between drugs seminal exposures and seminal plasma HIV load detectability was explored by ROC curves and multivariate logistic regressions.
Results: For FTC, 236 plasma concentrations (122 patients) and 209 SP concentrations (117 patients) were available. For TFV, 247 plasma concentrations (129 patients) and 217 SP concentrations (123 patients) were available. FTC and TFV plasma PK were best described by two-compartment models with linear elimination. Seminal plasma was modeled as an effect compartment with different input and output constants. FTC and TFV elimination clearances increased with creatinine clearance, and TFV elimination clearance decreased with lopinavir/ritonavir co-administration. No covariates were found to explain the PK variability in seminal plasma. Emtricitabine and tenofovir AUC0-24 in SP were higher than in plasma (median 38.14 vs 12.95 mg.h/L for FTC; 7.00 vs 2.99 mg.h/L for TFV). Median AUC0-24 ratios were 2.88 for FTC and 2.27 for TFV. Only 1 % of FTC AUC0-24 ratio were lower than 1 (CV = 54 %) for 12 % of TFV AUC0-24 ratio (CV = 125 %).
Conclusions: These are the first population-models describing FTC and TFV pharmacokinetics in plasma and SP. FTC and TFV concentrations in SP were higher than in plasma. TFV penetration in the male genital tract seems to be more variable than FTC penetration.
Reference: PAGE 24 () Abstr 3455 [www.page-meeting.org/?abstract=3455]
Poster: Drug/Disease modeling - Infection