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Safety and pharmacokinetics of dolutegravir in pregnant mothers with HIV infection and their neonates: A randomized trial (DolPHIN-1 study)

PLoS Medicine Oct 04, 2019

Waitt C, Orrell C, Walimbwa S, et al. - HIV-infected treatment-naïve 30 pregnant women in Uganda and South Africa were randomly assigned 1:1 to dolutegravir (DTG) or efavirenz (EFV)-containing ART until 2 weeks postpartum (2wPP), between March 9, 2017, and January 16, 2018, with follow-up until six months postpartum in order to evaluate the association between drug concentrations (pharmacokinetics, PK), including in breastmilk, and impact on viral suppression when begun in the third trimester (T3). Those who were on dolutegravir, intensive pharmacokinetic sampling was initiated at steady-state and postpartum, followed by a paired cord and maternal blood samples at delivery, and paired maternal plasma and breast milk, and infant plasma sampling. The high in-utero transfer was noted, and modest breastmilk transfer of dolutegravir to the infant. In infants in-utero and in the first two weeks of life, this, joined with the delayed elimination of dolutegravir in newborn infants, led to high dolutegravir exposure. In conclusion, irrespective of low plasma DTG exposures in the third trimester, transfer across the placenta and through breastfeeding was noted in this study, with constancy in infants expected because of delaying metabolic clearance. Furthermore, HIV RNA suppression < 50 copies/mL was twice as quick with DTG vs EFV, implying that in mothers who have begun treatment late in pregnancy, DTG has the ability to decrease the risk of vertical transmission.
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