Dilated Cardiomyopathy Associated With Simian AIDS in Nonhuman Primates

Abstract

Background —Cardiomyopathy is being recognized with increasing frequency in patients with AIDS, yet the relationship between HIV infection and cardiac contractile dysfunction remains obscure. The purpose of the present study was to determine if infection with simian immunodeficiency virus (SIV) in nonhuman primates is associated with cardiac dysfunction and myocardial injury. Methods and Results —Left ventricular size and function were determined by 2D echocardiography in 16 rhesus macaques before and at weekly intervals following infection with cloned pathogenic SIV mac 239 or the highly attenuated SIV mac 239 nef deletion mutant. A second group of 15 rhesus macaques chronically infected with pathogenic (n=6) or nonpathogenic (n=9) virus were studied at >2 years following infection. Cardiac tissues from 24 rhesus macaques chronically infected (>2 years) with pathogenic SIV were reviewed for evidence of cardiac pathology. Acute infection (<6 weeks) with either pathogenic or nonpathogenic SIV caused neither contractile dysfunction nor cardiac pathology. However, LV ejection fraction was significantly ( P <0.05) depressed (43±7%) in rhesus macaques chronically infected with pathogenic SIV compared with rhesus macaques chronically infected with nonpathogenic SIV (61±3%). Furthermore, two thirds of rhesus macaques that succumbed to simian AIDS had myocardial pathology including lymphocytic myocarditis (n=9) and coronary arteriopathy (n=6), with complete vessel occlusion (n=4) and associated myocardial infarction and necrosis. Conclusions —This unique model is valuable in understanding the pathogenesis of cardiac injury associated with retroviral infection in a relevant nonhuman primate model of AIDS.