A study from Botswana identified an elevated risk of neural tube defects (NTD) in infants of mothers with HIV treated with dolutegravir (DTG) around the time of conception. Comprehensive data from the United States, a setting with folic acid fortification of food, have not been reported.
We analyzed the IBM MarketScan Commercial Claims and Encounters Database and the Centers for Medicare and Medicaid Services data from 2008-2019. We identified pregnancies with enrollment during their whole duration among women aged 15-49y; for this cohort, we determined presence of HIV diagnosis and antiretroviral (ARV) prescriptions by type of ARV. We developed an algorithm to estimate time of conception, identify pregnancy outcomes, and match infants with NTD diagnoses to their mothers. We estimated incidence of NTD by type of ARV (DTG vs any other ARV) periconceptionally and during first trimester (8 weeks before conception -13 weeks gestation). As severe congenital defects can lead to prenatal death, we also estimated the incidence of stillbirths and spontaneous and induced abortions.
We identified 17,544,269 pregnancies (weighted) in MarketScan and 18,904,008 in Medicaid over the study period (Table); of these, 22,129 (0.1%) and 84,388 (0.4%) had a HIV diagnosis, respectively. Among these, 509 pregnancies in commercially insured women and 2,331 in Medicaid had early exposure to DTG. No NTDs were identified in commercially insured women, and one case (spinal bifida) was identified in Medicaid, with an incidence of 0.66 per 1,000 livebirths. The corresponding rates of NTD in infants of women without HIV were 0.76 per 1,000 in commercially insured women, and 0.91 per 1,000 in Medicaid. Similarly low rates of NTD were observed among women with HIV and early pregnancy exposure to other ARV (Table). Women with HIV had higher rates of stillbirths and pregnancy losses compared with women without HIV.
We studied the largest U.S. cohort of periconceptional/early pregnancy DTG exposures and provide compelling evidence on the safety of DTG during conception and early pregnancy. The results are reassuring, as they do not demonstrate an increased risk of NTD in the U.S., and support the current U.S. federal perinatal guidelines. In the absence of nationwide surveillance, the pregnancy algorithm we developed can be used with administrative databases to study correlates of rare outcomes such as NTD and to monitor adverse pregnancy outcomes of ARV use in U.S. women.