Objectives: HIV-infected patients have a greater burden of sub-clinical and clinical atherosclerotic disease compared to the general population. The primary objective of this study was to compare the relative roles of inflammation, endothelial alterations, and metabolic factors in the induction and maintenance of atherosclerosis in antiretroviral therapy (ART)-treated or ART-naive patients.
Design: Cross-sectional study; 79 HIV-infected patients (55 ART-treated and 24 naive individuals) were consecutively enrolled. In both groups, nearly 50% of the individuals had a high cardiovascular risk (Framingham value >20%).
Methods: Echo-Doppler [intima–media thickness (IMT)], inflammatory, thrombophilic, endothelial, metabolic indexes, and cholesterol efflux molecules were evaluated. Multivariate analysis adjusted for age, CD4 nadir, BMI, and Framingham's score were used to analyze the results.
Results: A complex pathogenesis drives atherogenesis in HIV infection. Thus, whereas inflammation could be responsible for this process in ART-naive individuals, metabolic factors [low-density lipoprotein (LDL), apolipoprotein B (ApoB), lipoprotein A] seem to play a more prevalent role in ART-treated patients. Notably, ABCA-1, an ATP-binding transporter cassette protein involved in cholesterol efflux, which is inhibited by Nef, is up-regulated in ART-treated individuals.
Conclusion: Atherosclerosis in HIV infection results from the interaction of multiple factors: an inflammatory and HIV-driven disease could prevail in the absence of therapy; metabolic, non-inflammatory causes may be more important in patients undergoing therapy. Approaches to atherosclerotic disease in HIV infection should consider these differences.
aInfectious Diseases Unit
bEndocrinology Unit, Luigi Sacco Hospital
cUniversity of Milano
dFondazione Don Gnocchi, Milan, Italy.
Correspondence to Professor Mario Clerici, MD, Chair of Immunology, University of Milano, Department of Biomedical Sciences and Technologies, Via F.lli Cervi 93, 20090 Segrate, Milan, Italy. Tel: +39 02 5031 9679; fax: +39 02 5031 9677; e-mail: email@example.com
Received 12 July, 2012
Revised 24 September, 2012
Accepted 25 September, 2012