Minimal impact of pregnancy on rilpivirine pharmacokinetics in women living with HIV.

OBJECTIVES

Rilpivirine, a non-nucleoside reverse transcriptase inhibitor for preventing mother-to-child HIV transmission, may have reduced plasma exposure in the second and third trimesters due to increased metabolism/elimination in pregnant women, potentially compromising its efficacy. The study aimed to evaluate maternal rilpivirine plasma concentrations during pregnancy and postpartum.

METHODS

A multicenter, cross-sectional, cohort was conducted from 2020 to 2023. Pregnant women living with HIV-1 receiving rilpivirine 25 mg once-daily containing regimen were enrolled. Plasma concentrations of rilpivirine were determined throughout pregnancy and postpartum. A population pharmacokinetic approach was performed to analyze the plasma concentrations. Rilpivirine trough plasma concentrations (C24h) were estimated using individual parameters and interpreted using an efficacy threshold of 48 ng/ml (# four-fold protein adjusted EC50).

RESULTS

Seventy-two (97% sub-Saharan African) pregnant women were enrolled: median age 34 years old (interquartile range 25-75%; 28-38). All were receiving triple-therapy, including emtricitabine/tenofovir (as tenofovir disoproxil fumarate or tenofovir alafenamide fumarate)-associated nucleoside reverse transcriptase inhibitors. Overall, 222 plasma concentrations were determined. There was no effect of gestational age or trimester on pharmacokinetic parameters to improve the between-occasion variabilities. Median rilpivirine estimated C24h were 79 ng/ml (interquartile range 25-75%; 55-105). Among the 72 women, 14% of them presented C24h<48 ng/ml. Only one woman presented >200 copies/ml viral load during her pregnancy.

CONCLUSIONS

In our study, no significant effect of pregnancy on rilpivirine pharmacokinetic parameters was reported. No dose adjustment for orally-administered rilpivirine should be recommended in this setting.