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NO INCREASE IN BIRTH DEFECTS IN INFANTS EXPOSED TO INTEGRASE INHIBITORS AT CONCEPTION
Jeanne Sibiude1, Jérôme Le Chenadec2, Laurent Mandelbrot1, Stephane Blanche3, Catherine Dollfus4, Nathalie Lelong5, Elisa Arezes6, Lamya Ait Si Selmi2, Sophie Matheron7, Christine Rouzioux8, Josiane Warszawski6, Roland Tubiana9
1Hôpital Louis-Mourier, Colombes, France,2INSERM, Le Kremlin-Bicetre, France,3AP–HP, Paris, France,4Hôpital Armand-Trousseau, Paris, France,5INSERM, Paris, France,6University of Paris-Sud, Orsay, France,7AP–HP, Hôpital Bichat-Claude Bernard, Paris, France,8Necker Hospital, Paris, France,9AP–HP, Hôpitaux Universitaires Pitié Salpêtrière, Paris, France
Integrase inhibitors (InSTI) are increasingly used by HIV-infected women during pregnancy. Following an alert on the association of dolutegravir with neural tube defects, we evaluated the risk of birth defects in case of exposure to this antiretroviral class.
The French Perinatal Cohort is a multicenter national cohort including all HIV-infected women in 90 maternities. We studied all mother-infant pairs exposed to InSTI, categorized into 3 groups: (G1) ongoing at conception, (G2) initiated during pregnancy, as first-line regimen, and (G3) initiated during pregnancy, as 2nd-line regimen. Within each group, we matched 1:1 to an InSTI-unexposed infant according to other drugs, ethnicity, center, year of delivery, and gestational age at ART-initiation. InSTI exposed women who did not receive PI or NNRTI were matched to women receiving darunavir, with the same other drugs. We compared birth defect rates between the 3 InSTI-exposed groups and, for each group, with the respective matched group, using chi2 and McNemar tests.
Overall, 309 infants were exposed to InSTI at conception (G1): 224 to raltegravir, 41 to dolutegravir, and 44 to elvitegravir. Birth defects rates for InSTI-exposed infants at conception (G1: 5.5% 17/309) did not significantly differ from those of InSTI-exposed infants of the two other groups: 2.7% (5/184) in G2 and 3.0% (10/329) in G3, p=0.18. There was no neural tube defect among infants exposed to InSTI at conception, and only two birth defects among the 41 infants exposed to dolutegravir (a case of Down syndrome, and a persistant ductus arteriosus). When restricting to matched infants, birth defect rates in G1 were not significantly different from the matched InSTI-unexposed group (6,3%, 12/189 vs 3,7%, 7/189, respectively, p=0.26). The EUROCAT types of birth defects were similar for InSTI-exposed at conception and matched infants. There was no difference in stillbirth rates (1.8% vs 0.4%, p=0.37), nor in preterm birth rates (14.3% vs 10.8%, p=0.29) between pregnancies exposed at conception and the matched pregnancies. Among women exposed at conception, 65% were still receiving InSTI at delivery. Similarly, there was no difference in birth defect rates between InSTI-exposed infants in G2 and G3 and the matched unexposed infants.
We found no evidence of a higher birth defect rate among 309 infants exposed to InSTI at conception, mostly exposed to raltegravir, however in the current context, surveillance must be pursued for this class of ART.