Jeanne Sibiude1,2, Jérôme Le Chenadec3, Laurent Mandelbrot1,2, Catherine Dollfus4, Sophie Matheron2,5, Nathalie Lelong6, Véronique Avettand-Fenoel7,8,9, Maud Brossard3, Pierre Frange9,10, Véronique Reliquet11, Josiane Warszawski3,12,13, Roland Tubiana14,15. 1. Service de gynécologie-obstétrique, AP-HP Hôpital Louis Mourier, Colombes. 2. Université de Paris, INSERM UMR1137, IAME, Paris. 3. Département d'Epidémiologie, Centre de Recherche en Épidémiologie et Santé des Populations, INSERM U1018, Université Paris-Saclay, APHP Public Health Department, Le Kremlin-Bicêtre. 4. Unité d'Hémato-oncologie, Hôpital Armand Trousseau, Groupe hospitalier Sorbonne Université. 5. Service des maladies infectieuses et tropicales, Hôpital Bichat, AP-HP. 6. INSERM U1153 (Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Biostatistics and Epidemiology), Maternité Port Royal. 7. Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine. 8. INSERM, U1016, CNRS, UMR8104, Institut Cochin. 9. AP-HP, Laboratoire de Microbiologie Clinique, Hôpital Necker-Enfants Malades. 10. EA7328 PACT, Institut Imagine, Université de Paris, Paris. 11. Service de Maladies Infectieuses et Tropicales, CHU Nantes. 12. Université Paris Saclay, Le Kremlin-Bicêtre. 13. Service de Santé publique, APHP, Le Kremlin Bicêtre. 14. Service de Maladies infectieuses et tropicales, APHP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix. 15. INSERM, Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France.
Abstract
OBJECTIVES: Following an alert on neural tube defects and dolutegravir, we sought to evaluate if the exposure integrase strand transfer inhibitors (INSTIs) at conception was associated with birth defects or other adverse pregnancy outcomes. METHODS: In the prospective national French Perinatal Cohort (EPF), we studied birth defects and other perinatal outcomes by matching each pregnant woman exposed to INSTIs with a pregnant woman exposed to darunavir/ritonavir receiving the same backbone of nucleoside reverse transcriptase inhibitors and matched for other characteristics such as age, geographic origin, centre and year of delivery. RESULTS: Among 808 women exposed to INSTIs during pregnancy (raltegravir = 703, dolutegravir = 57 and elvitegravir = 48), we reported a slightly higher rate of birth defects in infants exposed at conception to raltegravir (6.7%) vs. infants exposed to raltegravir later in pregnancy: 2.9% if initiated during pregnancy as first-line, and 2.5% as second-line treatment, P =0.04. When compared with matched controls, raltegravir exposure at conception was not significantly associated with birth defects: 6.4 vs. 2.3%, P = 0.08. There was no cluster of birth defect type and no neural tube defects were observed. Other perinatal outcomes, such as preterm birth and stillbirths, did not differ significantly between raltegravir-exposed women and matched counterparts. No difference in any outcome was observed for elvitegravir/cobicistat or dolutegravir. CONCLUSION: We found a nonsignificant trend for an association between exposure to raltegravir at conception and birth defects, which needs to be evaluated by larger prospective surveillance data, as these drugs are increasingly prescribed in women living with HIV.
OBJECTIVES: Following an alert on neural tube defects and dolutegravir, we sought to evaluate if the exposure integrase strand transfer inhibitors (INSTIs) at conception was associated with birth defects or other adverse pregnancy outcomes. METHODS: In the prospective national French Perinatal Cohort (EPF), we studied birth defects and other perinatal outcomes by matching each pregnant woman exposed to INSTIs with a pregnant woman exposed to darunavir/ritonavir receiving the same backbone of nucleoside reverse transcriptase inhibitors and matched for other characteristics such as age, geographic origin, centre and year of delivery. RESULTS: Among 808 women exposed to INSTIs during pregnancy (raltegravir = 703, dolutegravir = 57 and elvitegravir = 48), we reported a slightly higher rate of birth defects in infants exposed at conception to raltegravir (6.7%) vs. infants exposed to raltegravir later in pregnancy: 2.9% if initiated during pregnancy as first-line, and 2.5% as second-line treatment, P =0.04. When compared with matched controls, raltegravir exposure at conception was not significantly associated with birth defects: 6.4 vs. 2.3%, P = 0.08. There was no cluster of birth defect type and no neural tube defects were observed. Other perinatal outcomes, such as preterm birth and stillbirths, did not differ significantly between raltegravir-exposed women and matched counterparts. No difference in any outcome was observed for elvitegravir/cobicistat or dolutegravir. CONCLUSION: We found a nonsignificant trend for an association between exposure to raltegravir at conception and birth defects, which needs to be evaluated by larger prospective surveillance data, as these drugs are increasingly prescribed in women living with HIV.