HIV infection, HAART, and endothelial adhesion molecules: current perspectives.
In this review we summarise the data on the effects of HIV infection and its therapy with antiretroviral drugs on adhesion molecules, considered to be potential biomarkers of endothelial cell function. This is a recent area of interest, given the unexpected associations between antiretroviral therapy, metabolic alterations of lipid profile, and the risk of cardiovascular disease in the absence of clear pathogenetic links. Although convincing prospective data are still scarce, it seems timely to elucidate the potential value of non-invasive, inexpensive tests for predicting cardiovascular risk in HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Endothelial function, the most plausible link between infection, inflammation, and atherosclerosis, has been investigated since the beginning of the HIV epidemic. Increased concentrations of soluble adhesion molecules, such as those from the selectin and immunoglobulin families, have consistently been reported in HIV-positive patients. The introduction of HAART has renewed interest in the study of endothelial function in HIV-positive patients, in view of some HAART-related metabolic abnormalities (hyperlipidaemia, hyperglycaemia, fat redistribution) and several large reports of premature coronary artery disease. Whether HAART reduces endothelial injury associated with HIV infection or contributes to further endothelial cell activation is still a matter of controversy. Also unclear is whether HAART acts directly or indirectly, and if protease inhibitors and other classes of antiretroviral drugs differ in their proatherosclerotic effects. This article attempts to define the state of these emerging issues, identifies areas of controversy and of potential clinical relevance, and suggests some directions for future research.
de Gaetano Donati
Katleen
K
Department of Infectious Diseases, Catholic University Medical School, Rome, Italy. kdegaetanodonati@yahoo.com
Rabagliati
Ricardo
R
Iacoviello
Licia
L
Cauda
Roberto
R
D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001161:Arteriosclerosis / Q000139:chemically induced* / Q000209:etiology; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans
D015415:Biomarkers; D015815:Cell Adhesion Molecules