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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