4.7 Article

The role of immunity and inflammation in the progression of atherosclerosis in patients with HIV infection

Journal

STROKE
Volume 38, Issue 9, Pages 2477-2484

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.106.479030

Keywords

atherosclerosis; chemokine polymorphisms; HIV; intima media thickness; nonconventional cardiovascular disease risk factors

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Background and Purpose - The initial steps of atherosclerosis and the entry of HIV into the cell share similar biological mechanisms. Therefore, our hypothesis is that the progression of atherosclerosis in patients with HIV infection can be influenced by variations in genes implicated in both processes. Methods and Results - The progression of atherosclerosis over a 2-year follow-up period was measured as the combined carotid and femoral intima media thickness (IMT) in 141 patients with HIV infection. The Delta IMT ( IMTfollow-up - IMTbaseline) values were used to segregate patients as minimal progressors or regressors ( lowest Delta IMT tertile), slow progressors ( mid Delta IMT tertile), and rapid progressors ( highest Delta IMT tertile). Mutations CCR-5 Delta 32, CCR-2 64I, MCP-1-2518G, SDF1-3'A, and CX3CR-1 ( T280 mol/L and V249I) in the host DNA were determined. Mean age of the patients was 38.96 ( SEM: 0.61) and 68.8% were male. The mean Delta IMT was 0.045 mm ( 0.01) per year, which represented a significant progression ( P < 0.001) with respect to baseline values. Patients with minimal progression or regression had a significantly ( P = 0.01) higher CD4 cell count than slow progressors and rapid progressors. Multivariate analyses indicated that age and total cholesterol were positively associated with IMT progression. In contrast, the CD4 cell count, the SDF1-3'A, and the CX3CR-1 249 I mutated alleles were associated with lesser IMT progression. Conclusion - The course of atherosclerosis in patients with HIV infection is influenced by polymorphisms in the SDF1 and CX3CR1 genes by metabolic variables and by the CD4 cell count. These data would be of help in assessing therapeutic needs of these patients.

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