Background: Preliminary data from Tsepamo Botswana birth defects surveillance study identified potential neural tube defect (NTD) teratogenic signal in infants born to HIV-infected women receiving dolutegravir (DTG)-based antiretroviral therapy (ART) during the periconceptional period (before conception and into first trimester), compared with periconceptional non-DTG ART or women without HIV (0.67%, 0.12%, and 0.09%, respectively) (Jul2018 IAS Conference). This analysis aims to 1) describe CNS defect cases reported to APR, a voluntary, international, prospective exposure registry and 2) determine any increased risk by ART drug class.
Methods: Data on prospectively enrolled pregnancies (Jan1989 through Jul2018) with birth outcome are summarized. Birth defects are reviewed by a dysmorphologist, coded by modified Metropolitan Atlanta Congenital Defects Program criteria, classified by organ system and assigned exposure timing for each antiretroviral. CNS defects include NTD (myelomeningocele/spina bifida, anencephaly) and encephalocele which is reported separately from NTD.
Results: 20,064 pregnancies resulted in 20,413 fetal outcomes including 19,005 live births. Reported pregnancies are from North America (75%), Europe (8%), Africa (7%), South America (6%) and Asia (4%). Of the 19,005 live births with any ART exposure, 8,040 had periconceptional exposure, including 222 birth defect cases and 20 CNS defects (2 NTD and no encephalocele). See Table for drug class data.
Conclusions: Twenty CNS defects (2 NTD) were observed among 8,040 birth outcomes with periconceptional ART exposure. Overall and drug class frequencies are consistent with observed low NTD prevalence (0.01%-0.1%) in developed countries where food folic acid fortification and antenatal folic acid supplementation are prevalent, reducing overall NTD occurrence. However, the number of pregnancies enrolled in the APR with exposure to newer drug classes such as integrase inhibitors (InSTIs) are insufficient to rule out or confirm any potential association with NTD. Healthcare providers are encouraged to continue to report pregnancies with prospective antiretroviral exposures to the APR, especially those involving newer antiretrovirals.

[ ]