(231) A Target Trial of Pre-conception Switch from a Legacy Medication to a New Medication – An Application to Antiretroviral Therapy and Birth Outcomes

Background: In-utero exposure to certain medications have differential effects on adverse birth outcomes. The introduction of new medications with more favorable safety profiles offers an opportunity to reduce risk by switching from high- to lower-risk medications prior to pregnancy. For example, in-utero exposure to nevirapine (NVP) has been associated with particularly high risk of adverse birth outcomes compared with newer ART like dolutegravir (DTG) among individuals with HIV. However, it is unknown whether pre-conception switch from NVP to DTG can reduce risk.

Objectives: To emulate a target trial of pre-conception switch from a legacy high-risk medication (NVP) to a new lower-risk medication (DTG) among individuals with HIV on adverse birth outcomes.

Methods: The Tsepamo Study has performed birth outcomes surveillance at delivery sites in Botswana since 2014. Among individuals on legacy HIV medication (NVP) in 2016, when the programmatic switch to DTG as standard of care began, we compared those who switched to DTG and then became pregnant with those who did not switch prior to pregnancy. We estimated adjusted risk ratios (RRs) for stillbirth, neonatal death, preterm delivery, very preterm delivery, small-for-gestational-age (SGA), very SGA, and combined endpoints of any adverse or severe adverse outcome. We also evaluated low ( < 50kg) and high (≥80kg) early pregnancy weight and hypertension in pregnancy.

Results: Of 4,265 eligible individuals, 26% switched from NVP to DTG prior to pregnancy. Comparing switchers with non-switchers, RRs (95% CIs) were 0.82 (0.75, 0.89) for any adverse and 0.84 (0.71, 1.00) for any severe adverse outcome. These differences were driven by SGA (RR [95% CI]: 0.79 [0.69, 0.90]) and very SGA (RR [95% CI]: 0.77 [0.62, 0.96]). Switchers were less likely to have low (RR [95% CI]: 0.74 [0.57, 0.95]) and more likely to have high (RR [95% CI]: 1.34 [1.14, 1.57]) early pregnancy weight. Sensitivity analyses indicated little evidence for time-trends in birth outcomes over the study period.

Conclusions: Switching from legacy to new medications with more favorable safety profiles prior to conception can improve birth outcomes. Among individuals with HIV, switching from NVP to DTG prior to pregnancy may reduce the risk of low maternal weight in early pregnancy and fetal growth restriction.