Rilpivirine Plasma and Cervicovaginal Concentrations in Women During Pregnancy and Postpartum

Overview

Journal J Acquir Immune Defic Syndr

Specialty Infectious Diseases

Date 2018 Mar 13

PMID 29528944

Citations 11

Authors

Ahizechukwu C Eke

Nahida Chakhtoura

Angela Kashuba

Brookie M Best

Craig Sykes

Jiajia Wang

Alice M Stek

Elizabeth Smith

Samantha Calabrese

Edmund V Capparelli

Mark Mirochnick

Affiliations

Soon will be listed here.

Abstract

Background: Concentrations of antiretrovirals in the genital tract play a key role in preexposure prophylaxis. This study aims to describe rilpivirine (Edurant) concentrations in the genital tract in pregnant and postpartum women.

Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials Protocol P1026s is an ongoing, prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women that include a cohort receiving rilpivirine combination regimen. Intensive pharmacokinetics evaluations were performed at steady state during the second and third trimester, and postpartum. Plasma and directly aspirated cervicovaginal fluid (CVF) samples were collected at 4 time points around an observed dose and measured using high-performance liquid chromatography with ultraviolet detection, [plasma; lower limit of quantification (LLQ) = 10 ng/mL] or liquid chromatography-tandem mass spectrometry (CVF; LLQ = 1 ng/mL).

Results: A total of 24 women were included in the analysis. For all time points combined, median (interquartile range) rilpivirine concentrations were 70 ng/mL (23-121) in CVF and 92 ng/mL (49-147) in plasma. The CVF to plasma AUC(0-4) ratios were significantly higher in the second (0.90, 90% CI: 0.61 to 1.46) and third trimesters of pregnancy compared with postpartum (0.40, 90% CI: 0.19 to 0.87). Three of 189 (1.6%) plasma samples in 2 women were below the LLQ and the corresponding CVF concentrations. Seventeen additional CVF concentrations (10.6%) were below LLQ in 13 participants. No major safety concerns were noted.

Conclusions: Rilpivirine concentrations were higher in the CVF during pregnancy compared with postpartum. CVF Rilpivirine is likely to achieve inhibitory concentrations effective for preventing peripartum HIV transmission.

Citing Articles

Population pharmacokinetics of rilpivirine following oral administration and long-acting intramuscular injection in real-world people with HIV.

Thoueille P, Saldanha S, Schaller F, Choong E, Veuve F, Munting A Front Pharmacol. 2024; 15:1437400.

PMID: 39619609 PMC: 11605395. DOI: 10.3389/fphar.2024.1437400.

Physiologic Changes During Pregnancy and Impact on Small-Molecule Drugs, Biologic (Monoclonal Antibody) Disposition, and Response.

Eke A, Gebreyohannes R, Fernandes M, Pillai V J Clin Pharmacol. 2023; 63 Suppl 1:S34-S50.

PMID: 37317492 PMC: 10365893. DOI: 10.1002/jcph.2227.

Long-acting antiretrovirals and HIV treatment adherence.

Nachega J, Scarsi K, Gandhi M, Scott R, Mofenson L, Archary M Lancet HIV. 2023; 10(5):e332-e342.

PMID: 37062293 PMC: 10734401. DOI: 10.1016/S2352-3018(23)00051-6.

Prediction and prevention of preterm birth in pregnant women living with HIV on antiretroviral therapy.

Jones A, Eke U, Eke A Expert Rev Anti Infect Ther. 2022; 20(6):837-848.

PMID: 35196941 PMC: 9133156. DOI: 10.1080/14787210.2022.2046463.

An update on the physiologic changes during pregnancy and their impact on drug pharmacokinetics and pharmacogenomics.

Eke A J Basic Clin Physiol Pharmacol. 2021; 33(5):581-598.

PMID: 34881531 PMC: 9174343. DOI: 10.1515/jbcpp-2021-0312.

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