Effects of HIV Infection and Antiretroviral Therapy on the Heart and Vasculature

Both infection with human immunodeficiency virus (HIV) and treatment of HIV infection with antiretroviral drugs may affect the function of the heart and the vasculature. Direct infection of target tissues with HIV, inflammation and immunosuppression secondary to HIV infection, and common comorbidities, such as alcohol and drug abuse, may all contribute to impairment of function. Direct effects of antiretroviral drugs on the vasculature and indirect effects mediated through the metabolic complications of antiretroviral therapy (ART)1 also appear to contribute to this impairment. The landmark Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study found that use of HIV-1 protease inhibitors is associated with an increased risk of myocardial infarction,2 but only part of this increased risk is mediated by the circulating lipid disturbances these drugs induce. Thus, other mechanisms by which protease inhibitors cause endothelial dysfunction, insulin resistance, and enhanced atherosclerosis are likely to be involved. ### Effect of HIV Infection on the Developed Heart HIV infects myocytes but is not abundant (1 in ≥2000 cells) or highly multiplicative in these cells.3 Despite the paucity of evidence of direct myocyte involvement, HIV infection clearly causes structural and functional injury to the heart as a whole. The virus persists in reservoir cells in the cerebral cortex and in macrophages that may be present between myocardial cells, even after effective ART.4 Much of the evidence for HIV effects on the heart was published before the era of highly active ART (HAART), and thus, the beneficial effects on the heart of more thorough suppression of HIV infection with HAART are generally less well understood. Reservoir cells and associated cytokine signaling may be important in the development and progression of cardiomyopathy and encephalopathy. Reservoir cells may hold HIV on their surfaces for extended periods. It is also possible that the reservoir is in cytoplasmic vacuoles, with virus inducible …