Abstract 4365028: HIV Antiretroviral Therapy and Drinking Water Contaminant Exposures Induce Cardiac Function Changes in Women of Childbearing Age

Abstract

Objective: The majority of individuals living with human immunodeficiency virus (HIV) are female. Although combined antiretroviral therapy (cART) can greatly improve prognosis and prevent vertical transmission, the off-target cardiometabolic effects of these drugs in pregnant women and women of childbearing age remain understudied. Concurrent exposure to ubiquitous environmental pollutants, such as per and polyfluoroalkyl substances (PFAS), may interact with cART to impact maternal health, given their shared potential to affect mitochondria and the cardiovascular system. Our broader project investigates the combined impact of cART and a legacy PFAS compound, perfluorooctanesulfonic acid (PFOS), on cardiometabolic outcomes in a rat model. Here, we analyzed non-pregnant animals, which will later be compared to pregnant counterparts. Methods: Adult female Sprague-Dawley rats were exposed to a common cART regimen (abacavir/dolutegravir/lamivudine; Triumeq) or vehicle (aqueous methylcellulose/Tween 80). Dams were also given PFOS-contaminated water, mimicking concentrations measured in a North Carolina community, or vehicle (reverse osmosis-filtered water). Dams underwent echocardiography, electrocardiography, and subsequent tissue harvest on study day (SD) 27 or SD50. Tissue and plasma samples underwent PFAS quantification, pathological evaluation, RNA sequencing, and mitochondrial function analysis. Results: The nonpregnant cohort demonstrated perturbations in several structural and functional parameters by exposure group. The SD27 timepoint demonstrated shortened ejection times (48.20ms in cART vs 52.19ms for control), suggesting systolic dysfunction. In the combined exposure group, slower isovolumetric relaxation times (28.47mm vs 27.11mm) and higher ejection fractions (70.8% vs 68.9%) were seen compared to the control at SD27. Structurally, cART rats showed increased interventricular septal thickness, posterior wall thickness, and left ventricular (LV) mass across timepoints. At SD50, cART rats showed increased LV mass and heart weight:tibia length ratios, suggesting hypertrophy. Conclusion: Our data suggest cART and co-exposure to PFOS impact cardiac function in adult rats. While more prominent initially, the healthy unstressed heart seems to adapt to the drugs’ effects over time, although signs of hypertrophy remain. Analysis of the pregnant cohort will reveal whether the physiological strain of pregnancy sensitizes the cardiovascular system of the animals.