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Title
Periconceptional antiretroviral exposure and central nervous system (CNS) and neural tube birth defects - data from Antiretroviral Pregnancy Registry (APR)
Presenter
Lynne M. Mofenson, MD
Authors
L.M. Mofenson, MD1, V. Vannappagari2, A.E. Scheuerle3, B. Baugh4, K.P. Beckerman5, H. Betman6, N. Chakhtoura7, K. Dominguez8, A. Pikis9, N.S. Santanello10, W.R. Short11, C.T. Thorne12, H. Tilson13, V. Vinas14, H. Watts15, J.D. Albano16
Institutions
1Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, United States, 2ViiV Healthcare, Research Triangle Park, United States, 3University of Texas Southwestern Medical Center, Dallas, United States, 4Janssen Scientific Affairs, LLC, NYC, United States, 5Mt Sinai Bronx Lebanon Hospital, Bronx, United States, 6AbbVie, Chicago, United States, 7National Institutes of Health, Washington, DC, United States, 8US Centers for Disease Control and Prevention, Atlanta, United States, 9Food and Drug Administration, Washington, DC, United States, 10Independent Pharmacoepidemiologist, Philadelphia, United States, 11University of Pennsylvania, Philadelphia, United States, 12University College of London, London, United Kingdom, 13UNC School of Public Health, Chapel Hill, United States, 14Mylan Laboratories, Morgantown, United States, 15Office of the Global AIDS Coordinator and Health Diplomacy, Washington, DC, United States, 16Syneos Health, Raleigh, United States

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.



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