The Role of Immunity and Inflammation in the Progression of Atherosclerosis in Patients With HIV Infection

Abstract

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 ⌬IMT (IMT follow-up ϪIMT baseline ) values were used to segregate patients as minimal progressors or regressors (lowest ⌬IMT tertile), slow progressors (mid ⌬IMT tertile), and rapid progressors (highest ⌬IMT tertile). Mutations CCR-5⌬32, CCR-2 64I, MCP-1-2518G, SDF1-3ЈA, 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 ⌬IMT was 0.045 mm (0.01) per year, which represented a significant progression (PϽ0.001) with respect to baseline values. Patients with minimal progression or regression had a significantly (Pϭ0.01) 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 SDF1-3ЈA, 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.

Lipodystrophy: The Metabolic Link of HIV Infection with Insulin-Resistance Syndrome

“…Some authors suggested that the pathogenetic mechanism responsible for carotid lesions associated with HIV infection may be more similar to an inflammatory process than to the classical atherogenesis [204,205]. Some retrospective and prospective studies have shown that the incidence of myocardial infarction in HIV-positive subjects treated with ART tends to be higher than in the general population, particularly in those receiving a PI-based treatment [206].…”

Fractalkine Receptor/Ligand Genetic Variants and Carotid Intima-Media Thickness

“…One previous study found an inverse association of rs3732379 with carotid IMT progression in 141 HIVpatients. 7 We did not find any association of IMT with rs3732379, although we did not measure IMT progression. Another study observed a decreased CCA-IMT in homozygous rs3732378-variant carriers among 1256 individuals.…”

Gestione del rischio cardiovascolare nel paziente HIV positivo

“…La più rapida progressione della malattia aterosclerotica osservata in questi individui, responsabile della maggiore frequenza e della precoce insorgenza dell'infarto miocardico in questa popolazione rispetto alla popolazione generale, può derivare sia da fattori di rischio tradizionali, sia da fattori specifici HIV-associati. Se infatti è vero che tra le persone HIV-positive molti tradizionali fattori di rischio cardiovascolare (tra cui fumo di sigaretta, abuso di stupefacenti, ipertensione arteriosa, dislipidemia, insulino-resistenza, alcolismo) sono più frequenti, è altrettanto vero che l'infiammazione e l'immunoattivazione indotte dal virus possono causare una disfunzione endoteliale e un progressivo danno vascolare (6)(7)(8). La stessa cART infine può giocare un ruolo nell'eziopatogenesi della malattia cardiovascolare.…”