Pregnancy and neonatal outcomes following prenatal exposure to dolutegravir. Journal of Acquired Immune Deficiency Syndrome
Vannappagari et al. on behalf of the Antiretroviral Pregnancy Registry (APR) and the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) aimed to retrospectively assess fetal and neonatal outcomes following maternal dolutegravir use during pregnancy.
Of 265 pregnancies reported to the APR, initial exposure to dolutegravir occurred at conception or first trimester in 173 pregnancies and during the second or third trimester in 92 pregnancies. There were 246 (92.8%) live births resulting in 255 neonates (9 twins), 6 (2.3%) induced abortions, 11 (4.2%) spontaneous abortions, and 2 (0.8%) stillbirths. Birth defects occurred in 7 (2.7%) of 255 live-born neonates, 5 (3.1%) of 162 (includes 6 twins) with conception/first-trimester exposure.
Of 101 pregnancies reported to the EPPIC, outcomes were available for 84 pregnancies (16 continuing to term and 1 lost to follow-up). There were 81 live births (80 with known initial dolutegravir exposure at conception or first, second, and third trimesters in 42, 21, and 17 live births respectively), 1 stillbirth (second-trimester exposure), 1 induced abortion (first-trimester exposure), and 1 spontaneous abortion (first trimester exposure), respectively. Birth defects occurred in 4 live births (4.9%; 95% confidence interval: 1.4 to 12.2), 3 of 42 (7.1%) with exposure at conception or first trimester.
In conclusion, the assessment of these collective 198 birth outcomes after first-trimester dolutegravir exposure from 2 prospective registries (APR, 156 outcomes; EPPICC, 42 outcomes) and data cited from 3 other studies with 104 pregnancy outcomes identified no birth defect signal, either in defect prevalence or in defect-type clustering. In addition, among birth defects reported after dolutegravir exposure during pregnancy or at the time of conception, none involved the neural tube. These findings may provide some reassurance to women whose pregnancies have already been exposed to dolutegravir or who have limited therapeutic options but remain inconclusive because of small study sample sizes.