Antiretroviral Therapy at Conception Leads to Lower Peripheral CD49a ⁺ NK Cells and Higher SERPINB2

<b>Problem:</b> Antiretroviral therapy (ART) during pregnancy is essential to prevent vertical HIV transmission and preserve the health of the mother and child. However, ART in pregnancy has been associated with adverse birth outcomes linked to poor placental development. Immune dysregulation of placental development is an important factor in the development of preeclampsia (PE), a common hypertension disorder of pregnancy. Some studies found an association between ART use at conception or during the first trimester and PE. However, little is known regarding the impact of timing of ART initiation on the immune environment in pregnancy. <b>Methods:</b> To investigate the immune environment in pregnant persons with HIV (PPWH) on ART at conception (<i>N</i> = 40) compared to PPWH that started ART in the second trimester (<i>N</i> = 40) we analyzed specimens from the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Perinatal Core Protocol, P1025, concluded in 2013. <b>Results:</b> No difference was found in soluble factors in circulation including PlGF and sFLt-1, associated with PE. However, upon analysis of PBMC by high dimension flow cytometry, we detected a lower frequency of circulating CD49a⁺ NK cells, associated with uterine tissue and pregnancy, in PPWH on ART at conception compared with PPWH who started ART in the second trimester. Moreover, PBMC from PPWH on ART at conception expressed higher levels of SERPINB2 in transcriptomics analyses. <b>Conclusions:</b> Our findings shed new insights into the potential impact of ART at conception and suggest the persistence of a dysregulated inflammatory environment compared to PPWH starting ART after the conclusion of placental development.