Target trials of preconception switch from nevirapine or efavirenz-based antiretroviral therapy to dolutegravir-based antiretroviral therapy on adverse birth and maternal outcomes.

OBJECTIVE

To compare the effect of preconception switching from nevirapine (NVP) and efavirenz (EFV) to dolutegravir (DTG) based antiretroviral therapy (ART) on adverse birth and maternal outcomes.

DESIGN

Two target trial emulations using the Tsepamo Birth Outcomes Surveillance Study in Botswana.

METHODS

Among individuals who initiated NVP or EFV, we compared those who switched to DTG with those who did not switch prior to pregnancy. We estimated adjusted risk ratios and 95% confidence intervals (95% CIs) for any adverse birth outcome (stillbirth, neonatal death, preterm delivery, or small-for-gestational-age), any severe adverse birth outcome (stillbirth, neonatal death, very preterm delivery, or very small-for-gestational-age), low (<50 kg) and high (≥80 kg) early pregnancy weight, and maternal hypertension (SBP ≥140 or DBP ≥90 mmHg).

RESULTS

Comparing NVP to DTG switchers ( n  = 1054) with nonswitchers ( n  = 3163), risk ratios (95% CIs) were 0.81 (0.74-0.89) for any adverse birth outcome, 0.81 (0.68-0.96) for any severe adverse birth outcome, 0.74 (0.57-0.96) for early pregnancy weight less than 50 kg, 1.35 (1.15-1.59) for early pregnancy weight at least 80 kg, and 0.93 (0.82-1.06) for maternal hypertension. Comparing EFV to DTG switchers (n = 1,538) with nonswitchers ( n  = 7227), risk ratios (95% CIs) were 0.99 (0.91-1.07) for any adverse birth outcome, 1.05 (0.91-1.22) for any severe adverse birth outcome, 0.93 (0.78-1.12) for early pregnancy weight less than 50 kg, 1.22 (1.06-1.39) for early pregnancy weight at least 80 kg, and 1.29 (1.14-1.45) for maternal hypertension.

CONCLUSION

Preconception switch from NVP to DTG may reduce the risk of adverse maternal and infant outcomes. Switch from EFV to DTG had no clear associations with adverse infant outcomes but may increase the risk of maternal hypertension.