Evaluation of Neural Tube Defects (NTDs) After Exposure to Raltegravir During Pregnancy

OBJECTIVE: To evaluate the risk of neural tube defects (NTDs) after exposure to raltegravir during pregnancy. METHODS: Exposures to raltegravir during pregnancy reported cumulatively through May 31, 2018, to the company safety database were reviewed to identify cases of NTDs. This database includes all reports of pregnancy from Merck-sponsored clinical trials, spontaneous postmarketing reports, and non-interventional data sources, including the Antiretroviral Pregnancy Registry (APR). Reports were classified as prospective (before knowledge of pregnancy outcome) or retrospective (after knowledge of pregnancy outcome). We also reviewed data from 2 ongoing pregnancy cohorts. RESULTS: A total of 2426 pregnancies with reported outcomes were identified among women exposed to raltegravir: 1238 from the Merck database and 1188 from United Kingdom/Ireland and French pregnancy cohorts. Among all 2426 reports, 1991 were prospective. No cases of NTDs were identified among the prospective pregnancy reports, of which 767 were first trimester, including 456 in the periconception period (at or within 28 days after conception). Among the 435 retrospective reports, 3 NTD cases per APR criteria were identified (anencephaly, and 2 meningomyelocele), of which only one (meningomyelocele) was among exposures in the periconception period. Given the inherent limitations and bias of retrospective reports, it is not appropriate to calculate an incidence rate. CONCLUSIONS: Prospectively collected pregnancy outcome data do not suggest an association between raltegravir exposure in the periconception period and NTDs. The current data support the updated DHHS and EACS treatment guidelines for use of raltegravir as a preferred integrase inhibitor in all stages of pregnancy.