JLE

Médecine thérapeutique / Pédiatrie

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Tolerance to antiretroviral drugs during pregnancy Volume 19, issue 1, January-February-March 2016

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Author
Maternité Port Royal
Groupe Hospitalier Cochin-Broca-Hôtel Dieu
53, avenue de l’Observatoire
75014 Paris
France
* Tirés à part

Every year, around 900,000 pregnant HIV-infected women are treated with antiretrovirals. Evaluating tolerance for both the mother and the child is thus necessary. All antiretroviral molecules (ARVs) are able to cross the placenta, but with various rates of passage, which is high for nucleoside reverse transcriptase inhibitors (NRTI) but much lower for protease inhibitors. The potential teratogenicity of ARVs has led to efavirenz being classified as ‘category D’ by the FDA, recommending that it should be avoided during pregnancy, due to suspicions relating to neurological defects. Causality has not yet been clearly established. A significant association between zidovudine and congenital heart defects has been reported in three independent studies. As for the risk of preterm birth associated with ARVs, studies report conflicting results, but links to protease inhibitors have been reported on several occasions. Finally, in terms of abnormalities found at birth, transient macrocytic anaemia, mostly moderate but sometimes necessitating transfusion, has been described in infants exposed to zidovudine. Bone and renal toxicity need further evaluation regarding exposure to tenofovir since it is now widely prescribed for pregnant women, and a recent study has found lower bone density in neonates exposed to tenofovir. Finally, the fact that NRTIs may integrate into DNA has led to the discovery of their mitochondrial toxicity, as well as a genotoxic signature on the nuclear DNA of children exposed to zidovudine. All these side effects have progressively led to changes in recommendations for first-line therapy during pregnancy.