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AIDS. 2018 Mar 27;32(6):729-737. doi: 10.1097/QAD.0000000000001755.

Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV.

Author information

1
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California.
2
Harvard T.H. Chan School of Public Health, Center for Biostatistics in AIDS Research, Boston, Massachusetts.
3
University of Southern California School of Medicine, Los Angeles, California.
4
University of Colorado, Children's Hospital Colorado, Aurora, Colorado.
5
Baylor College of Medicine-Texas Children's Hospital.
6
University of Alabama at Birmingham, Birmingham, Alabama.
7
Maternal, Adolescent, and Pediatric Research Branch, National Institute of Allergy and Infectious Diseases.
8
Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, Maryland.
9
Children's Hospital Boston.
10
Boston University School of Medicine, Boston, Massachusetts, USA.

Abstract

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 AUC0-24,Cmax and C24 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 AUC0-24 during pregnancy was similar to, whereas trough concentrations were lower than, those seen in nonpregnant adults. Trough concentrations in pregnancy were well above dolutegravir EC90 (0.064 μg/ml). Dolutegravir readily crosses the placenta. Infant elimination is prolonged, with half-life over twice that of historical adult controls.

PMID:
29369162
PMCID:
PMC5854536
[Available on 2019-03-27]
DOI:
10.1097/QAD.0000000000001755
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