Abstract
Dolutegravir (DTG) is recommended and widely used during pregnancy for maternal viral suppression and preventing perinatal transmission of HIV. Our objective is to assess pregnancy and neonatal outcomes including birth defects following prenatal DTG use using real-world European data.
Dolomite-EPPICC is a multi-cohort European observational study of DTG use in pregnant women living with HIV and their infants. An analysis of prospectively collected data on all pregnancies with any prenatal DTG exposure and with birth outcomes was conducted among participating cohorts from Italy, Romania, the Russian Federation, Spain, Switzerland and UK/Ireland. Periconception exposure was defined as being within the first 6 weeks of gestation.
Overall, 550 pregnancies (540 singleton, 10 twin pregnancies) from 7 cohorts were included in the analysis resulting in 508 liveborn infants (491 singletons and 17 twins). Overall, 72.1% (365/506) pregnancies were in parous women. A total of 27 pregnancies ended in spontaneous abortion, 18 pregnancies were terminated and five ended in still birth. One termination was for neuronal migration disorder and severe microcephaly, with periconception DTG exposure. All stillbirths were exposed to periconception DTG, none with birth defects. Among the 508 liveborn infants, earliest DTG exposure was periconception for 326 (64.9%) infants, later in trimester 1 for 36 (7.2%) and in trimester 2/3 for 140 (27.9%); 6 had unknown timing of exposure. There were 21 infants with birth defects (4.1%, 95% CI 2.6, 6.2); one infant had 2 defects. The 22 defects were in the following systems: genitourinary (7), heart (4), limb (4 [polydactyly, 3]), gastrointestinal (2), chromosomal (1), other (4); no CNS defects were reported.
The prevalence rate for overall birth defects here is the same as recently reported from the Antiretroviral Pregnancy Registry for periconception exposure to DTG. Dolomite-EPPICC will continue to monitor use and safety of DTG-based regimens in pregnancy, noting that our sample size of periconception exposures is currently too small to exclude potential associations with rare birth defects like NTDs.