Rilpivirine Plasma and Cervicovaginal Concentrations in Women During Pregnancy and Postpartum

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.

Conflict of interest statement

Conflicts of Interest and Source of Funding:

1. Angela Kashuba, Professor of Pharmacotherapy and Experimental Therapeutics is funded by The University of North Carolina at Chapel Hill Center for AIDS Research (CFAR), an NIH funded program P30 AI50410.

2. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

3. For the remaining authors none were declared.

Figures

Figure 1. Rilpivirine Curves (2nd trimester, 3rd trimester, postpartum)

Figure 1 shows the rilpivirine curves, including the cervicovaginal fluid AUC, plasma concentration and CVF/plasma ratios across the 2nd trimester, 3rd trimester and postpartum. 2nd trimester vs postpartum, p=0.02; 3rd trimester vs postpartum, p=0.06

Figure 2. CVF and Plasma AUC Correlations

Figure 2 shows the cervicovaginal fluid and plasma AUC correlations