A new study published in The Journal of Antimicrobial Chemotherapy assessed the safety and activity profile of the drugs – atazanavir and darunavir, in pregnant women with human immunodeficiency virus (HIV) using data from a national observational study. This study evaluated 409 pregnant women with atazanavir exposure and 19 with darunavir exposure for laboratory measures and main pregnancy outcomes, for example: preterm delivery, low birthweight, non-elective cesarean section, and neonatal gestational age-adjusted birthweight Z-score. It was found that there were no differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, hemoglobin, alanine aminotransferase (ALT), total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol between the two groups. On the contrary, in the third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides and a higher total cholesterol/HDL cholesterol ratio, while exposure to atazanavir was associated with higher levels of plasma bilirubin. From the results, it was inferred that the two main HIV protease inhibitors (PIs) currently recommended by perinatal guidelines exhibit similar safety and activity in pregnancy, with no evidence of differences between the two drugs in terms of main pregnancy outcomes. It was suggested that, based on the minor discrepancies observed in laboratory measures, prescribing physicians may prefer either drug in specific scenarios where the varying impacts of treatment on lipid profile and bilirubin may have clinical relevance.