Vannappagari V et al. Pregnancy and Neonatal Outcomes Following Prenatal Exposure to Dolutegravir. J Acquir Immune Defic Syndr 2019; 81(4):371-378.

There have been concerns regarding the safety of dolutegravir (DTG) in pregnancy after data from the Tsepamo birth study in Botswana identified four cases of neural tube defects (NTDs) among 426 women who conceived while on DTG-based regimens. Consequently, the WHO and the DHHS guidelines recommend that DTG not be initiated during the first trimester – < 14 weeks and in non-pregnant women trying to conceive. This study included pregnancy data from the Antiretroviral Pregnancy Registry (APR) and the European Pregnancy and Pediatric HIV Cohort Collaboration (EPPICC). The APR included data from 70 countries including the U.S., which accounts for the majority of patients. There were 265 reports of DTG exposure from the APR of which 246 resulted in live births. From the EPPICC there were 101 pregnancies with outcomes data available on 84 births. Dolutegravir was initiated before or during the first trimester in 65% of women in APR and 58% in EPPICC. Birth defects were noted in 2.7% of infants from APR and 4.9% of those from EPPIC. However, there were no NTDs or other CNS abnormalities in any of the infants from either cohort. The authors believe these findings are reassuring regarding the use of DTG in pregnancy and are consistent with data from several other cohorts. They cite the need for more pregnancy data and larger sample sizes of women taking DTG.

Author’s Commentary: These data continue to show a lack of significant teratogenicity including CNS birth defects in infants exposed to DTG. An updated analysis of Tsepamo found that as of July 2018, there were no more cases of neural tube defects after 170 additional births with dolutegravir exposure at conception, providing an updated interim neural tube defect prevalence rate of 0.67%. The Dolphin-2 study presented this year at CROI also did not find any cases of NTDs in infants exposed to DTG. The DHHS perinatal guidelines may be updated again later this year when additional data becomes available on this issue. In the interim they do note that because of its very good resistance profile DTG is recommended by DHHS for women with acute HIV infection in pregnancy (after the first trimester) and for women who present to care late in pregnancy.