Comparative safety of dolutegravir-based or efavirenz-based antiretroviral treatment started during pregnancy in Botswana: an observational study

Summary Background Global rollout of dolutegravir-based antiretroviral therapy (ART) has been hampered in part by insufficient safety data in pregnancy. We compared birth outcomes among women initiating dolutegravir-based ART with those among women initiating efavirenz-based ART in pregnancy in Botswana. Methods In this observational study, we captured birth outcome data at eight government hospitals throughout Botswana (~45% of all deliveries in the country) in an ongoing study that started on Aug 15, 2014. In 2016, Botswana changed first-line ART from efavirenz-tenofovir-emtricitabine to dolutegravir-tenofovir-emtricitabine, including for pregnant women. This analysis includes women starting either efavirenz-based ART or dolutegravir-based ART during singleton pregnancy (regimen started and delivery occurring between Aug 15, 2014, and Aug 15, 2016, for efavirenz-based ART and between Nov 1, 2016, and Sept 30, 2017, for dolutegravir-based ART). We excluded births to mothers who had switched regimen or stopped ART. The primary outcomes were the combined endpoints of any adverse outcome (stillbirth, preterm birth [ Findings Our analysis included 1729 pregnant women who initiated dolutegravir-based ART and 4593 who initiated efavirenz-based ART. The risk for any adverse birth outcome among women on dolutegravir versus efavirenz was similar (33·2% vs 35·0%; aRR 0·95, 95% CI 0·88–1·03), as was the risk of any severe birth outcome (10·7% vs 11·3%; 0·94, 0·81–1·11). We found no significant differences by regimen in the individual outcomes of stillbirth, neonatal death, preterm birth, very preterm birth, SGA, or very SGA. Interpretation Adverse birth outcomes were similar among pregnant women who initiated dolutegravir-based and efavirenz-based ART. Dolutegravir-based ART can be safely initiated in pregnancy. Funding National Institutes of Health.