Kala S, Dunk C, Acosta S, et al. - Researchers here examined the effect of initiation of HIV protease inhibitor (PI)-based combination antiretroviral therapy (cART) at periconception on key events in early pregnancy, ie, decidualization and spiral artery remodeling. They evaluated two PIs, lopinavir and darunavir, which are currently offered as cART options in HIV-positive pregnancies, using an ex vivo human first-trimester placenta-decidua explant model, an in vitro human primary decidual cell culture system, and an in vivo mouse pregnancy model. Findings in both human ex vivo and mouse in vivo experimental models revealed impairment in uterine decidualization and spiral artery remodeling in correlation with lopinavir-based cART, but not with darunavir-based cART. The uterine endometrium had defective maturation in correlation with periconceptional initiation of lopinavir-cART, but not darunavir-cART, that results in impairments in spiral artery remodeling and placentation, and contributes to the poor birth outcomes.