Background: In May 2018, a potential risk of neural tube defects (NTD) in infants born to HIV-positive women exposed to dolutegravir (DTG) at pregnancy conception was announced. With widespread availability of DTG since 2016, Brazilian public health leaders initiated a national evaluation of birth outcomes of women exposed to DTG at conception.
Methods: Women who became pregnant while on ART containing DTG, efavirenz (EFV), or raltegravir (RAL) within +/- 8 weeks from estimated date of conception (EDC) between January 2015 and May 2018 were identified using the Brazilian ART database. Every woman with DTG exposure and three women receiving EFV-based antiretroviral therapy (ART) from similar locations were investigated. Trained personnel systematically collected demographic, medical, obstetric, radiographic, laboratory, and birth outcome data. The primary outcome was the occurrence of NTD; 95% Wilson confidence intervals (CI) were calculated. Characteristics at EDC and during antenatal care were evaluated.
Results: Overall, 1468 women were included, of which 382 were DTG-exposed and 1086 EFV- and/or RAL-exposed. At conception, DTG-exposed women were slightly younger, more recently diagnosed with HIV, had lower CD4 cell counts, and were less likely to have virological suppression. During pregnancy, 48 and 45% of DTG-exposed and -unexposed women, respectively, received folic acid supplementation. Prenatal syphilis occurred in 11% of DTG-exposed women (vs. 6% in unexposed, p< 0.01) and gestational hypertension occurred in 7% (vs. 3%, p< 0.01). There were a total of 1493 birth outcomes (Table 1). There were no NTD in either exposure group (0 [95%CI 0, 0.0099] in DTG-exposed and 0 [95%CI 0, 0.003] in DTG-unexposed). Twenty-five (6.5%) and 48 (4.3%) stillbirths/abortions occurred among DTG-exposed and -unexposed fetuses, respectively (p=0.09).
Conclusions: DTG-exposure was not associated with NTD in our cohort; the incidence of NTD is likely well under 1% among DTG-exposed HIV-positive women in Brazil. Ongoing pharmacovigilance of pregnancy outcomes from diverse settings is necessary for clarification of NTD risk associated with DTG.

 DTG exposed N=384DTG unexposed N=1109p value
Birth outcome, N (%)  0.01
- live birth359 (93.5)1061 (95.7) 
- stillbirth2 (0.5)16 (1.4) 
- abortion23 (6.0)32 (2.9) 
Neural tube defects0 (0)0 (0)NA
Gestational age in weeks, median (IQR)39 (38-39)39 (38-39)0.91
Birth weight in grams3011 (2745-3310)3050 (2741-3360)0.39
[Table 1: Birth outcomes by DTG exposure at conception]