Surveillance of congenital anomalies following exposure to Raltegravir or Elvitegravir during pregnancy in the UK and Ireland, 2008-2018.

Background: The indisputable benefits of antiretroviral therapy (ART) in the reduction of mother-to-child-transmission of HIV have to be carefully balanced with the risks of embryo-fetal toxicities due to fetal exposure to maternal ART. The recent report of a potential safety signal with dolutegravir use in pregnancy and potential increased rate of neural tube defects has raised the question of a potential class effect for integrase strand inhibitors. To contribute real-world evidence, we evaluated data on pregnant women receiving raltegravir (RAL) or elvitegravir (EVG) in the United Kingdom and Ireland. Methods: The National Study of HIV in Pregnancy and Childhood is a comprehensive population-based surveillance study collecting data on all HIV-positive pregnant women and their children. We collected data on all pregnancies exposed to an ART regimen containing RAL or EVG resulting in live birth, stillbirth, and induced abortion with an expected date of delivery between September 2008 and April 2018. Pregnancies were stratified into 3 groups of earliest exposure. Results: A total of 908 pregnancies were exposed to a RAL- or EVG-based regimen (875 to RAL and 33 to EVG). There were 886 live-born infants exposed to RAL, 8 pregnancies ended in stillbirth, and 9 in induced abortions. Among the 886 live-born infants, there were 23 (2.59%, 95% confidence interval: 1.65 to 3.86) reported congenital anomalies, 2 nervous system defects but no reported neural tube defects. Of the 33 pregnancies exposed to EVG, 31 resulted in live-born infants with no congenital anomaly and the remaining 2 pregnancies ended in induced abortion. Conclusions: The prevalence of congenital anomalies is consistent with national population estimates for 2008-2016 in the United Kingdom. More data are needed on safety of RAL and EVG in pregnancy.