In this study, we found that treatment-naïve individuals living with HIV present greater arterial stiffness compared to age- and sex-matched controls. This difference remained significant after adjusting for HR, MAP, BMI, and current smoking. Despite a greater cfPWV, we paradoxically found a tendency for lower brachial and central pulse pressure in the group living with HIV. We replicated previous findings on the harmful effect of HIV infection itself on the arterial vasculature but in a Mexican population. It is crucial to establish the effect of chronic infectious diseases in different populations such as HIV, given that the immune activation has been reported ̶ in some studies ̶ to vary between ethnicities . For example, compared to Caucasians, Hispanic individuals have been reported to present a greater prevalence of diabetes, insulin resistance , and greater average years of life lost after HIV infection . Currently, it is unknown whether Latin-American individuals living with HIV could develop, to a greater degree, metabolic abnormalities secondary to inflammation and accelerate arteriosclerosis.
4.1 Arterial stiffness
We found a significantly greater cfPWV treatment-naïve individuals living with HIV compared to controls, which agrees with previous reports in non-treated HIV infection [19, 40, 41]; however, others have reported similar cfPWV compared to controls [42-44]. As in our study, Schillaci et al.  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 . Chronic inflammation and greater oxidative stress impair NO by reducing its bioavailability; both processes present during HIV infection [47, 48]. A study with typhoid vaccine administration reported an increase in inflammatory cytokines and a decrease in antioxidant capacity, resulting in endothelial dysfunction . Furthermore, an animal study with superoxide dismutase (antioxidant) knock-out mice found that mice lacking the antioxidant exhibited progressively greater PWV over time compared to the wild type mice . In the early stages of HIV infection, it has been reported a reduction of the antioxidant glutathione , total antioxidant capacity, and increased peroxidation potential . Furthermore, a human study found that gamma-glutamyl transpeptidase, a serum enzyme associated with insulin resistance, liver disease, and oxidative stress, was associated with arterial stiffness.
Another mechanism that may cause arterial structural changes is through matrix metalloproteinase dysregulation (MMPs). MMPs are a group of endopeptidases that degrade components of the extracellular matrix, the collagen, elastin, laminin, and fibrillin in the arterial wall. Specifically, MMP-9 (gelatinase B) and MMP-2 have been associated with vascular remodeling . Both endopeptidases have been positively associated with aortic PWV in individuals with isolated systolic hypertension . One in vitro study reported that HIV-infected macrophages upregulate the secretion of MMP-9 by 3.1-fold compared to non-infected macrophages. More specifically, the HIV-derived proteins, envelope glycoprotein 120 (gp120), and Tat protein have been reported to stimulate MMP-9 expression [54, 55]. Although these endopeptidases were not assessed in our study, this mechanism could partially explain our findings.
A prospective study by Squillace et al.  explored the effect of two PI (atazanavir/ritonavir and lopinavir/ritonavir) regimens on markers of immune activation, adhesion molecules, and cytokine levels, and arterial function (endothelial function, PWV, and IMT). After a 6- and 18-month follow-up, pro-atherosclerotic chemokines and lymphocyte adhesion molecules (associated with plaque infiltration) increased in both treatment groups and no reduction in arterial function was observed. This study replicates the findings on the detrimental effects of PI on the vasculature .
The degree of immunosuppression has been associated with carotid arterial stiffness . In our HIV cohort, we observed that 63.6% of individuals had a lymphocyte T CD4+ count <500 cell/mm3, which may indirectly indicate a long-standing HIV infection before diagnosis; thus, a chronic and more detrimental effect on the vasculature.
4.2 Central hemodynamics
We found similar brachial and central BP between groups but lower cPP and a tendency to decreased pPP in the individuals living with HIV) group compared to controls. The lower central and brachial PP may be caused by a combination of a slightly reduced cSBP and pSBP and higher pDBP. A slight decrease in cSBP, despite greater PWV, could be explained by peripheral vasodilation (small and medium-sized arteries), possibly due to the vasodilating effect of prostaglandins [58, 59] and inflammatory cytokines (i.e., interleukin 1beta) , through NO-independent mechanisms  The vasodilation effect on peripheral reflection sites (e.g., arterial bifurcations) cause a decreased reflection of the backward wave and a reduced contribution to cSBP . However, Maloberti et al.  found no difference in cPP between controls and individuals living with HIV receiving ART or naïve to it. Only individuals living with HIV who received ART and presented chronic kidney disease had significantly greater cPP compared to controls. The lack of difference in their study might be due to an underpowered sample size to detect differences in cPP, as their HIV subgroup comparison was relatively small. Likewise, Vlachopoulos et al.  reported similar cPP and cfPWV; however, they did observe a reduced cSBP compared to uninfected individuals.
4.3 Lipid metabolism
Abnormal lipid metabolism after HIV infection is common and can be caused by the HIV infection itself, chronic inflammation, and ART (i.e., PI) [63, 64], which could lead to the development of metabolic syndrome (MetS). MetS is more prevalent in people living with HIV compared to non-infected, and further aggravated after ART . A study by Maloberti et al.  reported a higher prevalence of MetS in individuals with HIV receiving ART (19.4%) and treatment-naïve HIV individuals (13.8%) compared to controls (4.5%). However, only HIV individuals receiving ART showed hypertriglyceridemia and increased cfPWV. In our study, we found a tendency for lower TC, significantly lower HDL-c, and similar TG levels in treatment naïve HIV compared to uninfected controls. The majority of the individuals living with HIV in our study presented HDL-c below <1.04 mmol/L (78.2% vs. 21.8%) and TC below 5.2 mmol/L (60.8% vs. 39.2%) compared to the HIV(-) group, respectively. Arterial stiffness has been associated with dyslipidemia  and from the traditional risk factor point of view, hypertriglyceridemia and HDL-c play an essential role in the development of CVD in HIV. HDL-c provides atherogenic protection, prevents vascular inflammation  and oxidative stress ; thus, preserving endothelial function [69, 70]. A large cohort study found that HDL-c levels <1.04 mmol/L were associated with greater carotid stiffness compared to patients with normal or increased levels of HDL-c (>1.04 mmol/L) .
Previous findings of the effect of HIV on arterial stiffness have not been consistent. This can be due to several causes, including a pooled comparison of individuals receiving and not receiving ART and different methodologies to assess arterial stiffness such as brachial-ankle PWV  and one-point PWV . By exploring treatment-naïve individuals living with HIV, this study allowed us to exclude the potential negative effect of ART on the arterial system and evaluate the impact of HIV infection itself and traditional risk factors as potential etiologies. Our study has some limitations. Due to its cross-sectional design, we were unable to establish a causal relationship. The smoking history was statistically adjusted, and we were not able to assess the presence of MetS due to the absence of waist measurements. Future studies should evaluate biomarkers of inflammation or vascular disease before ART and assess their behaviour with different ART combinations in order to decrease the risk of CVD.