Maraviroc Reduces Arterial Stiffness in PI-Treated HIV-infected Patients

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. Whereas the aetiology of atherosclerosis in HIV is still unclear, it is well accepted that an excessive production of pro-inflammatory cytokines, likely triggered by microbial translocation, mediates this process2. Microbial translocation and high levels of pro-inflammatory cytokines were indeed 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 atherosclerosis3. Recent results have shown that the Δ32-CCR5 polymorphism, the first described genetic correlate of protection against HIV infection, is associated with an increased plasma concentration of high-density lipoprotein (HDL), a reduction of triglycerides in plasma4, and a reduced risk for coronary artery disease and myocardial infarction in the general population5. The likely role played by this genetic polymorphism in atherogenesis was reinforced by data obtained in the animal model. Thus, targeting CCR5 in dyslipidemic mouse models resulted in a significant reduction of both the atherosclerotic burden6 and the systemic secretion of proinflammatory Th1 cytokines. Further data indicating that RANTES, the natural CCR5 ligand, is detected on atherosclerotic plaques, myofibroblasts, and endothelial cells and is upregulated in late stages of atherosclerosis in both murine and human plaques lend further support to a role played by CCR5 in atherogenesis7. Notably, CCR5 also plays an important critical role in the late phases of atherogenesis, by inducing monocites trapping into the atherosclerotic lesions8. Maraviroc (MVC) is an antiviral drug that acts by targeting the CCR5 receptor, one of the key protein allowing HIV penetration into the target cells. 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. Notably, the use of MVC was also shown to result in a decline of plasma lipopolysaccharide in blood9,10,11. 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.