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 pPP and cPP 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 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 [41-43]. 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 [46, 47]. In animals, knock-out mice lacking superoxide dismutase (antioxidant) exhibited progressively greater PWV over time compared to the wild type mice . In humans, a study showed that acute inflammation caused by typhoid vaccine administration resulted in endothelial dysfunction . Moreover, in the early stages of HIV infection, it has been reported a decrease in glutathione  and total antioxidant capacity and increase in peroxidation potential  and gamma-glutamyl transpeptidase  – 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  and increased aortic PWV  ̶ have been reported to present a 3.1 fold increase in HIV-infected macrophages and stimulated by HIV-derived proteins: envelope 120 and Tat [53, 54].. . 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.  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 . 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.
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 the HIV(-) group. 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 [57, 58] and inflammatory cytokines (i.e., interleukin 1beta) , through NO-independent mechanisms . The vasodilation effect on peripheral reflection sites (e.g., arterial bifurcations) might cause a decreased reflection of the backward wave and a reduced contribution to cSBP . Maloberti et al.  reported similar cPP between controls and individuals living with HIV receiving ART or naïve to it, except for those with chronic kidney disease; however, their cPP subgroup comparison was relatively small Likewise, Vlachopoulos et al.  reported similar cPP and cfPWV; however, they did observe a reduced cSBP in treatment-naïve HIV(+) 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) [62, 63], 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 . 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%). 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 <1.04 mmol/L (78.2% vs. 21.8%) and TC <5.2 mmol/L (60.8% vs. 39.2%) compared to the HIV(-) group, respectively. Arterial stiffness has been associated with dyslipidaemia  , in particular, hypertriglyceridemia and HDL-c play an essential role in the development of CVD. HDL-c provides atherogenic protection, prevents vascular inflammation  and oxidative stress ; thus, preserving endothelial function [68, 69].
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 and traditional risk factors.
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 basal waist measurements. In addition, factors such as unemployment, education, and socioeconomic status have been associated with arterial health, and where not measured in our study participants. Future studies should evaluate the behaviour of biomarkers of inflammation or vascular disease in response to different ART combinations to better understand their effects on the vasculature.