Antiretroviral treatment (ART) guidelines depend upon safety data in pregnancy. Although developed countries have moved to dolutegravir (DTG)-based first-line ART for non-pregnant adults, the World Health Organization (WHO) still recommends efavirenz (EFV)/emtricitabine (FTC)/tenofovir (TDF) while awaiting safety data for DTG that may harmonize guidelines for pregnant and non-pregnant adults. In June 2016, Botswana became the first country in Africa to switch to DTG/TDF/FTC as first-line ART for adults, including pregnant women. This change occurred in the setting of ongoing NIH-supported birth outcomes surveillance at 8 sites throughout Botswana (R01HD080471), which was designed to evaluate adverse birth outcomes by ART regimen and neural tube defects by EFV exposure status. This surveillance system has already provided initial safety data for the DTG roll-out, and has raised concerns about the safety of specific nevirapine- and lopinavir/ritonavir- based ?legacy? ART regimens in pregnancy. Botswana's change to DTG/TDF/FTC, combined with the government's plan to switch women off ?legacy? ART starting in 2018, opens new scientific opportunities for this surveillance system. We are therefore applying for a new R01 to continue (and enhance) birth outcomes surveillance in Botswana. Our proposal has the following primary aims: 1) to perform the first large analysis of adverse birth outcomes and congenital abnormalities following DTG exposure from the time of conception, and 2) to evaluate birth outcomes among women who either continue ?legacy? ART or switch to DTG/TDF/FTC prior to (or during) pregnancy. These novel aims take advantage of the unique ART landscape in Botswana (including an upcoming plan to switch women off legacy ART regimens), and build on the emerging scientific findings from our highly productive surveillance system. Data generated from this study will be critical for updating WHO (and US) guidelines for the use of ART among pregnant women, and for women who may become pregnant.
Study Narrative The World Health Organization has prioritized research on the safety of dolutegravir (DTG) exposure in pregnancy, and Botswana is the only country currently using DTG-based antiretroviral treatment (ART) in pregnancy. In our ongoing surveillance in Botswana, we have identified concerning rates of adverse birth outcomes among women receiving older ART regimens, and we have reported on the safety of the initial DTG roll-out among pregnant women. We propose continuation of nationwide birth outcomes surveillance in Botswana, adding new scientific aims to take advantage of its unique antiretroviral treatment landscape.
