Abstract
The Δ32-CCR5 deletion of the CCR5 receptor is protective toward coronary artery pathology and myocardial infarction. Maraviroc (MVC), a CCR5 antagonist, was recently introduced in the therapy of HIV infection; we evaluated whether this drug could modulate the atherosclerotic burden in aviremic PI-treated HIV-positive individuals who underwent MVC intensification. Thus, the effect of MVC on intima media thickness, arterial stiffness, metabolic parameters, pro-inflammatory cytokines, endothelial dysfunction, and microbial traslocation markers was analyzed in 6 aviremic PI-treated HIV-positive individuals and were compared to those obtained in 9 additional aviremic PI-treated subjects that were enrolled retrospectively from our outpatients cohort. MVC intensification resulted in a significant reduction in intima media thickness, pulse wave velocity and triglycerides compared to baseline. Notably, MVC was also associated with a significant reduction of IL-6, microbial translocation indexes, sICAM and sVCAM; these changes were maintained throughout the 6 months of MVC intensification. No significant modifications were observed in CD4 counts, HIV viral load, and cholesterolemia. Results herein support a role of CCR5 antagonists in reducing the cardiovascular risk in HIV-infection. The hampering of inflammation, microbial translocation and the improvement of endothelial function could justify the protective role of CCR5 antagonists on atherosclerotic burden.
Highlights
HIV infection is associated with a high burden of cardiovascular disease that results both from a direct consequence of HIV itself and from the use of highly active antiretroviral treatment and, in particular, of ritonavir-boosted protease inhibitors (PI)[1]
The PI group was characterized at baseline by a significantly better IMT (p = 0.004 right carotid; p = 0.011 left carotid) and a significantly better Pulse wave velocity (PWV) compared to the MVC intensification group (p = 0.003) (Fig. 1)
Results of this study show that six months of MVC intensification in PI-treated individuals results in a positive effect on the atherosclerotic burden, possibly reverting the progression of atherosclerosis
Summary
HIV infection is associated with a high burden of cardiovascular disease that results both from a direct consequence of HIV itself and from the use of highly active antiretroviral treatment and, in particular, of ritonavir-boosted protease inhibitors (PI)[1]. Microbial translocation and high levels of pro-inflammatory cytokines were shown to be closely associated with several cardiovascular risk factors in HIV-infected individuals, including dyslipidemia, insulin resistance, hypertension, coagulation abnormalities, endothelial dysfunction, and carotid atherosclerosis[3]. Recent results have shown that the use of this drug reduces the progression of atherosclerosis in a dyslipidemic ritonavir-treated mouse model by interfering with inflammatory cell recruitment into the plaques. To evaluate whether MVC could have a beneficial effect on the atherosclerotic burden of HIV-infected individuals, we analysed the results of its implementation on intima media thickness, arterial stiffness, metabolic parameters, inflammatory cytokines, endothelial dysfunction and microbial translocation markers in PI-treated HIV-positive individuals
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