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J Acquir Immune Defic Syndr. 2016 Jul 1;72(3):289-96. doi: 10.1097/QAI.0000000000000968.

Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women.

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*Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA; †Skaggs School of Pharmacy and Pharmaceutical Sciences, Pediatrics Department-Rady Children's Hospital, University of California, San Diego, CA; ‡Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA; §Department of Biostatistics, Harvard School of Public Health, Boston, MA; ‖Department of Medicine, Children's Hospital Boston, Boston, MA; ¶Irmandade da Santa Casa de Misericordia de Porto Alegre, HIV/AIDS Research Department, Porto Alegre, Brazil; #Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; **FHI 360, IMPAACT Operations Office, Durham, NC; ††Program for HIV Prevention and Treatment, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; ‡‡Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, DHHS, Bethesda, MD; §§National Institute of Allergy and Infectious Diseases, Bethesda, MD; and ‖‖Department of Pediatrics, Boston University School of Medicine, Boston, MA.



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.


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.


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%).


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.

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