Background: Dolutegravir holds major advantages for antiretroviral therapy (ART), in resistance profile, tolerability and cost. However, safety concerns of its use in pregnancy pose significant ethical and equity issues, especially in low-and-middle income countries, where the majority of people living with HIV are women of child-bearing age.
Methods: We describe pregnancy outcomes in the ongoing South African ADVANCE trial (NCT03122262), a 96-week, phase 3 clinical trial assessing the safety and efficacy of 1053 patients randomised to dolutegravir-tenofovir alafenamide fumarate-emtricitabine (DTG-TAF-FTC); dolutegravir-tenofovir-emtricitabine (DTG-TDF-FTC), or efavirenz-tenofovir-emtricitabine (EFV-TDF-FTC). All women were on ART before conception, had gestational age assessment and congenital anomaly screen during pregnancy and at birth. Women on dolutegravir were switched to alternative regimens if < 8 weeks gestation. Adverse events included spontaneous abortion, elective termination, preterm birth (< 37 weeks), small for gestational age (SGA; < 10th percentile of weight for gestational age), stillbirth or neonatal death (< 28 days from delivery), and birth defects. Infant HIV status was also assessed
Results: Two thirds (43/65) of pregnancies occurred in women on a dolutegravir-based regimen. Of the 65 pregnancies, there were 28 (43.1%) live births, 8 (12.3%) spontaneous abortions, 16 (24.6%) elective terminations, and 11 (16.9%) pregnancies are ongoing. One neonatal death and 1 stillbirth occurred in the DTG-TAF-FTC and EFV-TDF-FTC treatment arms respectively. Median birth weights were similar across treatment arms. Overall 7.1% of infants were born prematurely and 17.2% of births were SGA. Two infants had minor birth defects (naevus flammeus and umbilical hernia) in the dolutegravir-containing arms. No HIV transmissions occurred.
Conclusions: Women who initiated dolutegravir-based ART before conception did not have higher rates of adverse pregnancy outcomes. These data add to limited evidence on the safety of dolutegravir in pregnancy. As there are other similar trials underway, it is important to pool data and to provide regular updates as data accrue.



[Table 1. Pregnancy and infant outcomes of women who became pregnant in the ADVANCE trial ]