Pharmacokinetics of Rilpivirine in HIV-Infected Women During Pregnancy and Postpartum

Background: Rilpivirine (RPV), a 2^nd generation non-nucleoside reverse transcriptase inhibitor, has increased absorption when taken with food and is primarily metabolized by cytochrome P450 3A4. During pregnancy, physiological changes including alterations in intestinal transit time and increased CYP 3A4 activity may impact systemic drug exposure. The impact of pregnancy on RPV pharmacokinetics (PK) is unknown.

Methods: IMPAACT Protocol P1026s is an ongoing, multicenter, non-blinded prospective study evaluating the PK of antiretrovirals (ARV) in pregnant HIV-infected women that included a cohort of US pregnant women receiving as part of clinical care combination ARV regimens including RPV 25 mg once daily with food. Intensive steady-state 24 hour PK profiles were performed during the 2^nd trimester, 3^rd trimester and 6-12 weeks postpartum. Maternal and umbilical cord blood samples were obtained at delivery. Plasma RPV concentrations were measured using liquid chromatography-mass spectrometry, with a lower limit of quantitation of 0.010 mcg/mL. The minimum target for RPV AUC₂₄ was 0.88 mcg*hr/mL, the 10^th percentile AUC for non-pregnant adults. Pairwise comparisons within each subject between time points were performed using a two-sided Wilcoxon signed rank test.

Results: RPV PK data were available for 26 women. PK parameters are presented in the table below as median (range). There were no significant differences in any PK parameters for the 2^nd or 3^rd trimester compared to postpartum. Mean (90% CI) for the ratio of 2^nd or 3^rd trimester to postpartum log-transformed pk parameters were 1.05 (0.78-1.32) and 1.01 (0.77-1.24) for AUC and 0.94 (0.69-1.18) and 0.91 (0.70-1.12) for C(24)h, respectively. Median (range) RPV concentrations (mcg/mL) in cord blood and maternal delivery samples, and their ratio were 0.054 (BQL (below quantitation limit) – 0.102), 0.103 (BQL – 0.234) and 0.53 (0.38 – 0.83). RPV was well tolerated by all study mothers. Viral load at delivery was below 400 copies/mL for 22 of 24 women and below 50 copies/mL for 17 of 24. No infants were HIV infected, but infection data through the final 24 week visit are only available for 7 infants.

Conclusions: No significant differences in RPV exposure during pregnancy and postpartum were observed. The standard RPV dose provides adequate RPV exposure during pregnancy.

RPV PK Parameters