Antiretroviral therapy in the peripartum period impairs post pregnancy cardiac reverse remodeling in a rodent model.

Cardiovascular (CV) disease is the leading cause of maternal mortality worldwide and has been partially linked to the cardiometabolic remodeling required to support fetal growth. In healthy pregnancies, these adaptations reverse postpartum without long-term consequences; however, impaired reverse remodeling (RR) increases future CV risk. Pregnant women living with HIV face additional risk, though it remains unclear whether this is driven by chronic low-level viremia or continuous antiretroviral therapy (ART). ART used during pregnancy often includes nucleoside reverse transcriptase inhibitors (NRTIs), which can affect mitochondria - organelles essential for maintaining cardiac function. Here, we tested the hypothesis that NRTI-containing ART negatively impacts the maternal heart. Using a rat model, we show that ART impairs pregnancy-associated cardiac RR. Mechanistically, ART induced mitochondrial alterations in both the heart and the liver, leading to dyslipidemia that collectively compromised cardiac function. These findings emphasize the importance of maternal cardiovascular health research and the need for further studies on the long-term effects of ART.