Abstract
ObjectiveTo determine the transplacental pharmacokinetics of the HIV integrase inhibitor dolutegravir.Study designMaternal-to-fetal transfer across the term human placenta was investigated with the ex-vivo dually perfused cotyledon model, in 5 closed-circuit, recirculating experiments. Dolutegravir was added to a maternal perfusate containing antipyrine, a marker to validate the cotyledon’s viability, and 2 g/liter of human albumin.ResultsAfter 3h of recirculating perfusion, the mean (± SD) DTG concentrations in the maternal and in the fetal compartments were respectively 2450 ± 286 ng/mL and 715 ± 369 ng/mL, with a fetal-to-maternal ratio of 34% ± 18% and a clearance index (in comparison with antipyrine transfer) of 79% ± 23%. The mean cotyledon accumulation index was 153% ± 25%.ConclusionFetal transplacental exposure to dolutegravir was considerable as well as accumulation in placental tissue. Whether this may lead to risks for the exposed fetus requires more investigation.
Highlights
Sustained suppression of plasma viral load is the key to preventing vertical transmission from HIV-infected women to their children
Fetal transplacental exposure to dolutegravir was considerable as well as accumulation in placental tissue. Whether this may lead to risks for the exposed fetus requires more investigation
Antiretroviral therapy is clearly recommended for all HIV infected pregnant women [2], but the choice of which medications to use must take into account the tolerance for the developing fetus, in view of the placental transfer of the drugs used [3]
Summary
Maternal-to-fetal transfer across the term human placenta was investigated with the ex-vivo dually perfused cotyledon model, in 5 closed-circuit, recirculating experiments. Dolutegravir was added to a maternal perfusate containing antipyrine, a marker to validate the cotyledon’s viability, and 2 g/liter of human albumin
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