Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV

Nikki Mulligan, Brookie M. Best, Jiajia Wang, Edmund V. Capparelli, Alice Stek, Emily Barr, Shelley L. Buschur, Edward P. Acosta, Elizabeth Smith, Nahida Chakhtoura, Sandra Burchett, Mark Mirochnick

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Objective: To evaluate dolutegravir pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. Design: Ongoing, nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and infants. Methods: Intensive steady-state 24 h pharmacokinetic profiles after dolutegravir 50 mg once-daily were performed during the second trimester (2T), third trimester (3T) and postpartum. Maternal delivery and postnatal infant samples were collected after birth. Dolutegravir was measured by validated LC-MS/MS; quantitation limit was 0.005 μg/ml. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-subject comparisons. Results: Twenty-nine enrolled participants had a median age of 32 years (range 21-42). Pharmacokinetic data were available for 15 (2T), 28 (3T) and 23 (postpartum) women. Median dolutegravir AUC 0-24, C max and C 24 were 25-51% lower in the 2T and 3T compared with postpartum. The median cord blood/maternal plasma concentration ratio was 1.25 (n = 18). In 21 infants, median elimination half-life was 32.8 h after in utero exposure. Viral load at delivery was less than 50 copies/ml for 27/29 women (93%). Twenty-nine infants were HIV-negative. Renal abnormalities noted on ultrasound in two infants were deemed possibly related to dolutegravir. Conclusion: Dolutegravir exposure is lower in pregnancy compared with postpartum in the same women on once-daily dosing. Median AUC 0-24 during pregnancy was similar to, whereas trough concentrations were lower than, those seen in nonpregnant adults. Trough concentrations in pregnancy were well above dolutegravir EC 90 (0.064 μg/ml). Dolutegravir readily crosses the placenta. Infant elimination is prolonged, with half-life over twice that of historical adult controls.

Original languageEnglish (US)
Pages (from-to)729-737
Number of pages9
Issue number6
StatePublished - Mar 27 2018


  • HIV infection
  • Tivicay
  • dolutegravir
  • integrase inhibitor
  • perinatal transmission
  • pharmacokinetics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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