We found a greater cfPWV in treatment-
naïve individuals living with HIV compared to controls, which agrees with previous reports in non-treated HIV infection [
19,
39,
40]; however, others have reported similar cfPWV compared to controls [
31,
41,
42]. As in our study, Schillaci et al. [
43] found, besides increased cfPWV, lower BMI, and HDL-c in individuals living with HIV without ART. A greater aortic stiffness, in our studied population, could be a combination of functional and structural changes in the arterial wall. Arterial stiffness is a complex phenomenon where different factors intervene, such as endothelial dysfunction, smooth muscle vascular tone, and structural changes. One of the mechanisms that regulate endothelial function is nitric oxide (NO). NO produces vasodilation, inhibits inflammation, and prevents thrombosis [
44]. Chronic inflammation and greater oxidative stress impair NO by reducing its bioavailability; both processes present during HIV infection [
45,
46]. In animals, knock-out mice lacking superoxide dismutase (antioxidant) exhibited progressively greater PWV over time compared to the wild type mice [
47]. In humans, a study showed that acute inflammation caused by typhoid vaccine administration resulted in endothelial dysfunction [
8]. Moreover, in the early stages of HIV infection, it has been reported a decrease in glutathione [
48] and total antioxidant capacity and increase in peroxidation potential [
49] and gamma-glutamyl transpeptidase [
18] – the latter associated with oxidative stress.
Another mechanism that may cause arterial structural changes is through matrix metalloproteinase (MMPs) dysregulation, which can which can degrade the collagen, elastin, laminin, and fibrillin within the arterial wall. Specifically, MMP-9 and MMP-2 ̶ associated with vascular remodelling [
50] and increased aortic PWV [
51] ̶ have been reported to present a 3.1 fold increase in HIV-infected macrophages and stimulated by HIV-derived proteins: envelope 120 and Tat [
52,
53]... Although these endopeptidases were not assessed in our study, this mechanism could partially explain our findings.
Some current ART regimes have shown to have negative effects on the vasculature. A prospective study by Squillace et al. [
54] reported that two PI regimens (atazanavir/ritonavir and lopinavir/ritonavir) increased pro-atherosclerotic chemokines, lymphocyte adhesion molecules and no improvement in arterial function after a 6–18 month follow-up.. On the other hand, the degree of immunosuppression has been associated with carotid arterial stiffness [
55]. In our HIV cohort, we observed that 63.6% of individuals had a CD4
+ T-cells count < 500 cells/μL, which may indirectly indicate a long-standing HIV infection before diagnosis; thus, a chronic and more detrimental effect on the vasculature.