Antiretroviral therapy in the peripartum period impairs post pregnancy cardiac reverse remodeling with early signs of heart failure with preserved ejection fraction

Abstract

Cardiovascular (CV) disease in pregnancy is the leading cause of maternal mortality worldwide, often associated with the cardiometabolic remodeling needed for fetal growth. In healthy pregnancies these changes reverse postpartum with no consequence, but improper reverse remodeling increases long-term CV risk. Pregnant patients with HIV are at further risk, but it remains unclear whether this is due to chronic low viremia or administration of antiretrovirals (ART). ART used in pregnancy includes nucleoside reverse transcriptase inhibitors (NRTIs), which have known mitochondrial toxicity, and may impact cardiac function. Here, we tested the hypothesis that NRTI-containing ART negatively impacts the maternal heart. Using rats, we show that pregnancy-associated reverse remodeling was impaired by ART. Molecularly, we found mitochondrial changes in the heart and in the liver, leading to dyslipidemia that collectively affected the heart. Our data suggest caution in the choice of ART prescribed for women with HIV during pregnancy and highlight the importance of studies focusing on maternal health.