Outcomes After Prenatal Exposure to Raltegravir-Containing Antiretroviral Therapy: A Multicohort European Study

Background: Raltegravir is an HIV integrase strand transfer inhibitor recommended for use in pregnancy. The aim of this study was to assess risk of birth defects and other suboptimal outcomes after prenatal exposure to raltegravir. Methods: We used pooled, prospectively collected individual patient data from studies in the European Pregnancy and Paediatric Infections Cohort Collaboration. Pregnancies with any prenatal exposure to raltegravir with outcomes in 2008-2020 were included. Birth defects were classified according to World Health Organization's International Classification of Diseases and EUROCAT criteria. Earliest prenatal exposure timing was classified as periconception [exposure at ≤6 completed gestational weeks (GWs)], later first trimester (T1) (exposure in T1 at >6 completed GWs), and second/third trimester (exposure at >12 completed GWs). Results: A total of 1499 pregnancies across 9 cohorts were included. Where timing was available (n = 1449), earliest raltegravir exposure was in the periconception period for 505 (34.8%), later T1 in 65 (4.5%), and T2/T3 in 879 (60.7%). The overall prevalence of birth defects among live-born infants with prenatal raltegravir exposure was 3.9% (95% confidence interval: 2.9, 5.0) (1443/1466) (International Classification of Diseases), with no increased risk observed for those exposed in the periconception period (P = 0.290). Among singleton live-born infants, 11.9% (160/1346) were born preterm, 11.3% (148/1307) low birthweight, and 8.6% (111/1291) small for gestational age, with no difference in outcomes observed by timing of raltegravir exposure. Conclusions: These findings add to the evidence base around safety of raltegravir use in pregnancy, although ongoing safety monitoring is needed to rule out risk of rare outcomes.