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    The recent HIV-1 NNRTI doravirine is likely to be used in pregnant women despite the complete lack of data on safety and exposure in the fetus. The objective of this study was to determine its placental transfer. Maternal-to-fetal transfer was investigated using the open-circuit ex vivo dually perfused human cotyledon model. Doravirine was added to a maternal perfusate (theoretical doravirine concentration of 250 ng/mL) containing 2 g/L human albumin and 20 g/L antipyrine, a marker to validate the cotyledon's viability, and cotyledons were dually perfused for up to 90 min. In five experiments, the median (IQR) doravirine concentrations in the maternal and fetal compartments were, respectively, 303 (178-420) and 40 (30-54) ng/mL, the fetal-to-maternal ratio was 16% (12%-18%) and the clearance index (in comparison with antipyrine transfer) was 48% (35%-64%). The median accumulation index in cotyledon tissue was 39% (range 10%-66%). Doravirine both crosses and accumulates in the placenta. This may be useful as pre/post-exposure prophylaxis to reduce the risk of vertical HIV transmission but carries the potential for fetal toxicities. Further investigation is required to determine the safety and efficacy of this new antiretroviral agent in pregnancy. © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

    Citation

    Minh Patrick Lê, Lucile Pencolé, Gilles Peytavin, Florian Bouchet-Crivat, Laurent Mandelbrot. Placental transfer of doravirine, a recent HIV-1 NNRTI in the ex vivo human cotyledon perfusion model. The Journal of antimicrobial chemotherapy. 2021 Aug 12;76(9):2364-2367

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    PMID: 34151361

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