BACKGROUND: The Tsepamo study last reported neural tube defect (NTD) data collected through March 2019 (Zash et al, NEJM 2019), with 0.3% prevalence following exposure to dolutegravir at conception compared with 0.1% following exposure to non-DTG antiretrovirals at conception. The study is ongoing and data collected through April 2020 are now reported.
METHODS: The Tsepamo Study conducts birth outcomes surveillance study at government hospitals throughout Botswana, currently covering ~70% of all births. Midwives perform surface examinations of all live births and stillbirths and describe abnormalities. Research assistants photograph major abnormalities after maternal consent, which are reviewed by a birth defects expert blinded to exposures. Prevalence of NTDs was determined by maternal HIV and antiretroviral exposure status (95%CI by Wilson method) and the primary analysis evaluated prevalence differences by exposure status (95%CI by Newcombe method).
RESULTS: Since March 2019, 39,200 additional births were recorded, including 1908 additional DTG conception exposures. Since August 2014, there have been a total of 158,244 deliveries; 153,899 (97.2%) had an evaluable infant surface exam, with 126 (0.08%, 95%CI 0.07%, 0.09%) NTDs identified (83 with photo, 43 by description only). Among women on dolutegravir at conception, 7/3591 NTDs occurred (0.19%; 95%CI 0.09%, 0.40%): 3 myelomeningoceles, 1 anencephaly, 2 encephaloceles, and 1 iniencephaly. In comparison, NTDs occurred in 21/19,361 (0.11%; 95%CI 0.07%, 0.17%) women delivering on any non-dolutegravir antiretrovirals from conception, 8/10,958 (0.07%; 95%CI 0.03%, 0.17%) on efavirenz from conception, 2/4,581 (0.04%; 95%CI 0.1%, 0.16%) on dolutegravir started in pregnancy, and 87/119,630 (0.07%; 95%CI 0.06, 0.09%) HIV-uninfected women. NTD prevalence differed non-significantly between dolutegravir and any non-dolutegravir antiretrovirals from conception (0.09% difference; 95%CI -0.03%, 0.30%).

CONCLUSIONS: After a period of decline since the original safety signal, prevalence of NTDs among infants born to women on dolutegravir at conception may be stabilizing at approximately 2 per 1000.