Pregnancy and Neonatal Outcomes Following Prenatal Exposure to Dolutegravir

Vani Vannappagari, MBBS, MPH, PhD; Claire Thorne, MSc, PhD; for APR and EPPICC


J Acquir Immune Defic Syndr. 2019;81(4):371-378. 

In This Article

Abstract and Introduction


Background: Birth outcome data with dolutegravir exposure during pregnancy, particularly in the first trimester, are needed.

Setting: Data were prospectively collected from the Antiretroviral Pregnancy Registry and European Pregnancy and Paediatric HIV Cohort Collaboration.

Methods: We reviewed 2 large, independent antiretroviral pregnancy registries to assess birth outcomes associated with maternal dolutegravir treatment during pregnancy.

Results: Of 265 pregnancies reported to the Antiretroviral Pregnancy Registry, initial exposure to dolutegravir occurred at conception or first trimester in 173 pregnancies and during the second or third trimester in 92 pregnancies. There were 246 (92.8%) live births resulting in 255 neonates (9 twins), 6 (2.3%) induced abortions, 11 (4.2%) spontaneous abortions, and 2 (0.8%) stillbirths. Birth defects occurred in 7 (2.7%) of 255 live-born neonates, 5 (3.1%) of 162 (includes 6 twins) with conception/first-trimester exposure. Of 101 pregnancies reported to the European Pregnancy and Paediatric HIV Cohort Collaboration, outcomes were available for 84 pregnancies (16 continuing to term and 1 lost to follow-up). There were 81 live births (80 with known initial dolutegravir exposure at conception or first, second, and third trimesters in 42, 21, and 17 live births, respectively), 1 stillbirth (second-trimester exposure), 1 induced abortion (first-trimester exposure), and 1 spontaneous abortion (first-trimester exposure), respectively. Birth defects occurred in 4 live births (4.9%; 95% confidence interval: 1.4 to 12.2), 3 of 42 (7.1%) with exposure at conception or first trimester.

Conclusions: Our findings are reassuring regarding dolutegravir treatment of HIV infection during pregnancy but remain inconclusive because of small sample sizes.


Dolutegravir is an integrase strand transfer inhibitor approved for the treatment of HIV-1 infection in adults and children aged older than 6 years or weighing >30 kg as part of combination antiretroviral (ARV) therapy.[1,2] Safety and efficacy of dolutegravir exposure during pregnancy have not been studied in randomized controlled trials because pregnancy was an exclusion criterion in all phase III dolutegravir trials.[3–7]

The Tsepamo birth study in Botswana compared birth outcomes of 4593 pregnant women starting efavirenz/tenofovir disoproxil fumarate/emtricitabine during pregnancy between August 2014 and August 2016 with those of 1729 pregnant women starting dolutegravir/tenofovir disoproxil fumarate/emtricitabine during pregnancy between November 2016 and September 2017.[8] In adjusted analyses, the dolutegravir-based regimen had a similar safety-risk profile for adverse birth outcomes when compared with efavirenz-based regimens. In addition, among 280 women starting dolutegravir-based ART and 395 starting efavirenz-based ART during pregnancy, only 1 major congenital abnormality occurred: skeletal dysplasia in an efavirenz-exposed infant. However, the study only reported data on exposure to dolutegravir after conception. In May 2018, after an interim analysis of Tsepamo study data conducted to inform the World Health Organization guidelines development group, a potential safety signal was identified with 4 cases of neural tube defects reported among infants born to 426 women who conceived while on dolutegravir-based regimens.[9]

This study assessed fetal and neonatal outcomes following maternal dolutegravir use during pregnancy by using prospective data from the Antiretroviral Pregnancy Registry (APR) and pregnancy cohorts participating in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC).