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SUBSTANTIALLY LOWER RILPIVIRINE PLASMA CONCENTRATIONS DURING PREGNANCY
Angela Colbers1, Stein Schalkwijk1, Deborah Konopnicki2, Andrea Gingelmaier3, John Lambert4, Ineke van der Ende5, José Moltó6, David M. Burger1
1Radboud Univ Med Cntr, Nijmegen, Netherlands,2Saint-Pierre Univ Hosp, Brussels, Belgium,3Klinikum der Univ München, München, Germany,4Mater Misericordiae Univ Hosp Dublin, Dublin, Ireland,5Erasmus Univ Med Cntr, Rotterdam, Netherlands,6Fundació Lluita Contra la Sida, Badalona, Spain
During pregnancy adequate antiretroviral exposure is important to prevent treatment failure, resistance and mother-to-child transmission (MTCT). However, pregnancy-related physiological changes may result in decreased antiretroviral exposure. Limited data is available on the pharmacokinetics (PK) of rilpivirine (RPV) during pregnancy. We aimed to study the PK of RPV during pregnancy, including placental transfer.
An open-label, multi-centre phase IV study in HIV-1-infected pregnant women recruited in HIV treatment centers in Europe (PANNA Network). Patients treated with RPV 25mg once daily during pregnancy had intensive steady-state 24-hour PK profiles in the third trimester and postpartum. RPV was taken with food. When feasible, cord blood and matching maternal blood samples were taken at delivery to asses placental transfer. RPV plasma concentrations were determined with a validated LC-MS method. The proposed minimum effective concentration of RPV was 0.04 mg/L (based on ECHO/THRIVE PK data).
Fifteen patients (10 black, 2 white, 2 Asian and 1 other) with a median (range) age of 30 (19-36) years were included in the analysis. Median (range) gestational age at delivery was 40 weeks (38-42); birth weight was 3480 (2770-4470) gr. Approaching delivery all patients had a VL <50 cps/mL. No children were HIV-infected, no birth defects were reported. 15 PK curves during 3rd trimester and postpartum were available. Geometric Mean Ratios (90% confidence interval) of PK parameters third trimester/postpartum were: 0.53 (0.45-0.63) for AUC0-24; 0.63 (0.54-0.74) for Cmax; and 0.46 (0.37-0.56) for C0h. Two out of 15 patients had a sub-therapeutic C0h in the third trimester, no sub-therapeutic levels were observed postpartum. The median (range, n=5) ratio of cord blood/maternal plasma RPV concentrations was 0.5 (0.35-0.81).
In this study exposure to RPV was about 50% lower in the third trimester of pregnancy, however, in this limited number of patients, maternal VL was suppressed close to delivery and no MTCT took place. It is important that RPV is taken with a meal during pregnancy and we would advice TDM in the third trimester to avoid sub-therapeutic exposure.