Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women

Anna H. Tran, Brookie M. Best*, Alice Stek, Jiajia Wang, Edmund V. Capparelli, Sandra K. Burchett, Regis Kreitchmann, Kittipong Rungruengthanakit, Kathleen George, Tim R. Cressey, Nahida Chakhtoura, Elizabeth Smith, David E. Shapiro, Mark Mirochnick, Shelley Buschur, Chivon Jackson, Mary Paul, Donna McGregor, Ram Yogev, Rohit KalraClaudia Florez, Patricia Bryan, Monica Stone, Andrew D. Hull, Mary Caffery, Stephen A. Spector, Joan Wilson, Julieta Giner, Margaret A. Donnelly, Ellen R. Cooper, Debra A. McLaud, Lisa F. Tucker, Jane Hitti, Amanda Robson-Nuss, Ann J. Melvin, Margaret A. Keller, Michael A. Bolaris, Judy Hayes, Françoise Kamer, La Shonda Spencer, James Homans, Torri Metz, Jenna Wallace, Alisa Katai, Mariam Aziz, Maureen McNichols, Julie Schmidt, Diane Wara, Kristinalisa Maka, Deborah Cohan, for the IMPAACT P1026s Protocol Team

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Background: Rilpivirine pharmacokinetics is defined by its absorption, distribution, metabolism, and excretion. Pregnancy can affect these factors by changes in cardiac output, protein binding, volume of distribution, and cytochrome P450 (CYP) 3A4 activity. Rilpivirine is metabolized by CYP3A4. The impact of pregnancy on rilpivirine pharmacokinetics is largely unknown. Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is a multicenter, nonblinded, prospective study evaluating antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving rilpivirine 25 mg once daily as part of their combination antiretrovirals for clinical care. Thirty-two women were enrolled in this study. Intensive pharmacokinetic sampling was performed at steady state during the second trimester, the third trimester, and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. Plasma rilpivirine concentration was measured using liquid chromatography-mass spectrometry; lower limit of quantitation was 10 ng/mL. Results: Median (range) AUC0-24 were 1969 (867-4987, n 15), 1669 (556-4312, n 28), and 2387 (188-6736, n 28) ng·h/mL in the second trimester, the third trimester, and postpartum, respectively (P < 0.05 for either trimester vs postpartum). Median (range) C24 were 63 (37-225, n 17), 56 (<10-181, n 30), and 81 (<10-299, n 28) ng/mL (P < 0.05 for either trimester vs postpartum). High variability in pharmacokinetic parameters was observed between subjects. Median (range) cord blood/maternal concentration ratio was 0.55 (0.3-0.8, n 21). Delivery HIV-1 RNA was ≤50 copies per milliliter in 70% and ≤400 copies per milliliter in 90% of women. Cmin were significantly lower at 15 visits with detectable HIV-1 RNA compared with 61 visits with undetectable HIV-1 RNA, 29 (<10-93) vs 63 (15-200) ng/mL (P 0.0001). Cmin was below the protein binding-adjusted EC90 concentration (12.2 ng/mL) at 4 visits in 3 of 31 women (10%). Conclusions: Rilpivirine exposure is lower during pregnancy compared with postpartum and highly variable. Ninety percent of women had minimum concentrations above the protein binding-adjusted EC90 for rilpivirine.

Original languageEnglish (US)
Pages (from-to)289-296
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Issue number3
StatePublished - Jul 1 2016


  • HIV
  • pharmacokinetics
  • pregnancy
  • rilpivirine

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)


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