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Title
Neural tube defects and major external structural abnormalities by antiretroviral treatment regimen in Botswana: 2014-2022
Presenter
Rebecca Zash
Authors
R. Zash1,2,3, M. Diseko2, L.B. Holmes4, D. Jacobson3, E. Caniglia5, S. Brummel6, G. Mayondi2, J. Mabuta2, C. Fennell3, T. Makoni1, T. Gaolathe7,2, S. Lockman8,3,2, J. Makhema2,6, R. Shapiro3,2,1
Institutions
1Beth Israel Deaconess Medical Center, Boston, United States, 2Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana, 3Harvard TH Chan School of Public Health, Center for Biostatistics in AIDS Research, Boston, United States, 4MassGeneral Hospital for Children, Boston, United States, 5University of Pennsylvania Perelman School of Medicine, Philadelphia, United States, 6Harvard TH Chan School of Public Health, Boston, United States, 7University of Botswana, Gaborone, Botswana, 8Brigham and Women's Hospital, Division of Infectious Diseases, Boston, United States

BACKGROUND: The Tsepamo Study reported a preliminary safety signal associating neural tube defects (NTDs) with dolutegravir (DTG) exposure from conception in 2018. We now report complete data through August 2022.
METHODS: Tsepamo conducts birth outcomes surveillance at public hospitals in Botswana (>2/3 of births in the country). During routine care, all live infants and stillbirths have a surface examination. Study staff record descriptions of abnormal exams, and exposures to maternal HIV and antiretrovirals; photograph abnormalities (with maternal consent); and review findings with a medical geneticist. NTDs include meningocele, myelomeningocele, anencephaly, encephalocele and iniencephaly. Abnormalities are ‘major’ if there is medical, surgical or cosmetic significance. Primary analyses evaluated age-adjusted prevalence differences (aPD) with 95% confidence intervals using a binomial model with identity link.
RESULTS: From 15 August 2014 to 15 August 2022, there were 235,727 deliveries; 235,286 (99.8%) had an evaluable infant surface exam, 162 (0.07%, 95% CI 0.06%, 0.08%) had an NTD and 1455 (0.62%, 95% CI 0.59%, 0.65%) had major external structural abnormalities. Among 11,110 exposures to conception-DTG there were 12 NTDs overall (0.11%, 95% CI 0.06%, 0.19%), similar to all non-DTG ART conception exposures (N=24,368, aPD -0.02%, 95% CI -0.09%, 0.05%)(Figure). The prevalence of NTDs with conception-DTG exposure (0.40%) among conceptions in the year after the DTG rollout (2017) was higher than subsequent years (range 0.06%-0.10%), (p<0.01). Among DTG-conception exposures, the prevalence of factors known to be associated with NTDs (maternal age, diabetes, weight >90kg, antiepileptic medication, folic acid supplementation at conception) was similar in 2017 and other years. The prevalence of major external structural abnormalities was similar between DTG-conception and non-DTG conception exposures (0.77% vs. 0.76%, aPD -0.04%, 95% CI -0.24%, 0.15%).


CONCLUSIONS: There was no detectable increase in NTDs or major external structural abnormalities among more than 11,000 exposures to DTG at conception captured in the Tsepamo Study from 2014-2022.

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