Atherosclerosis is associated with multiple pathogenic mechanisms in HIV-infected antiretroviral-naive or treated individuals.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Infectious Diseases Unit, University of Milano, Milan, Italy.
Stefania
S
Piconi
Serena
S
Parisotto
Giuliano
G
Rizzardini
Simone
S
Passerini
Paola
P
Meraviglia
Monica
M
Schiavini
Fosca
F
Niero
Mara
M
Biasin
Paolo
P
Bonfanti
Elena Delfina
ED
Ricci
Daria
D
Trabattoni
Mario
M
Clerici
D019380:Anti-HIV Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018791:CD4 Lymphocyte Count; D059168:Carotid Intima-Media Thickness; D003430:Cross-Sectional Studies; D018450:Disease Progression; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012307:Risk Factors
D019380:Anti-HIV Agents; D008077:Lipoproteins, LDL