ABC | Volume 114, Nº1, January 2019

Original Article Leite et al. Carotid thickness in HIV-infected patients Arq Bras Cardiol. 2020; 114(1):90-97 accounted for 59.6% of those infected with HIV and 75% of the control group. Comparing the characteristics of the groups, there were differences in inflammatory markers IFN- γ , IL-1, and TNF- α , with higher levels in the control group. Regarding CIMT, there was no significant difference between the groups, and distribution of gender as well as smoking and diabetes status were similar among them. The following two variables had borderline significance: levels of HDL cholesterol were higher among patients with HIV, while mean LDL was lower in this group. In the HIV-positive group, 37% of patients had less than five years of ART, 29.3% between 5 and 10 years, and 33.7% more than 10 years. Regarding CD4 levels and viral load during study admission, 90.5% of the subjects had CD4 levels above 350cells/mm 3 and all had undetectable viral load. Among the therapeutic regimens with NRTIs analogues, 98 (98.98%) of themcontained lamivudine, 65 (65.65%) contained zidovudine, 32 (32.32%) contained tenofovir, and three (3.03%) contained didanosine. For NNRTIs, 93 (93.93%) used efavirenz and six (6.06%) used nevirapine (Table 1). In HIV-infected individuals, higher HDL and LDL levels, CIMT, CD4+ T cell counts, and ART time were observed in older individuals (Table 2). The 75 th percentile calculated for 115 patients was 0.61 mm. Therefore, the CIM was considered thickened if > 0.61 mm. In the HIV-positive group, CIMT ≥ 0.61 mm was detected in 51 individuals (51.51%), of whom 78.4% were aged 40 years old or older. For the non-HIV group, the presence of IMT ≥ 0.61 mm was 56.25% (nine subjects), and 88.9% of these patients were 40 years old or older. Although it was evidenced that HIV‑infected individuals were aged 40 years old or older were associated with increased carotid thickness, a comparison between crude and Mantel–Haenszel odds ratios showed that the association between older age and thickness is independent of the infection status. Higher levels of total and LDL cholesterol were associated with CIMT ≥ 0.61 mm in the non-HIV group (Table 3). In the multivariate analysis, after adjustments for age, smoking status, and cholesterol level were made, a significant association with TNF- α levels was observed. Thus, increased levels of TNF- α were associated with greater chance of atherosclerosis. Individuals with increased IL1- β levels had greater chance of atherosclerosis with p-value close to significance (Table 4). Discussion To our knowledge, this is the first study to evaluate inflammatory biomarkers with the presence of CIMT only in individuals considered at low cardiovascular risk, with exclusive use of NRTIs and NNRTIs, and with undetectable HIV-1 RNA viral load in a population of HIV-infected patients. In the univariate analysis, it was found that inflammatory biomarkers (IFN- γ , IL-1 β , and TNF- α ) were higher in the non‑HIV group. These data are in contrast to the ones by Ross et al., 2 who found that TNF- α , hs-CRP, IL-6, and sVCAM‑1 were significantly higher in the HIV-infected group. Bethan et al. 11 also observed higher elevation of IL-6 and C‑reactive protein in HIV-positives as compared with controls. Our study excluded patients with detectable viral load, which is a contributing factor to the increase of these markers. In contrast, the studies cited did not use detectable viral load as an exclusion criterion, and it may have been an influencing factor in the discordance of the results. Samples obtained from plasma donors before, during, and after HIV acquisition demonstrated elevations in various cytokines during viral expansion, 12 and the initiation of ART in chronic infection is associated with a decline in the circulating levels of some cytokines, including IL-1 β , IL-6, and TNF- α , possibly by reduction of viral load. 13 An important limitation of the present study is the fact that the non- HIV group consisted of older individuals as compared with the infected ones. This factor may have contributed to the determination of higher levels of the abovementioned inflammatory markers and total and LDL cholesterol and consequently may have also skewed the results of the association of total and LDL cholesterol with CIMT ≥ 0.61 mm. However, it is worth noting that there is a great divergence in several studies under lipidogram changes in HIV‑infected individuals 2,14 . For example, in the study by Ross et al., 2 the HIV-infected group had lower mean HDL, but total cholesterol, triglycerides, and LDL were similar between the groups. LDL and triglyceride levels were positively correlated with CIMT. HIV-infected individuals had significantly higher triglyceride values and lower values of total cholesterol, HDL, and LDL as compared with the control group. 14,15 It has been shown that individuals over 40 years of age presented significantly higher total cholesterol, HDL and LDL levels, and higher mean CIMT, reinforcing that older age is a factor associated with its altered thickness measurement. CIMT means showed no statistically significant difference when compared to individuals with and without HIV. Lorenz et al. 16 demonstrated higher CIMT mean in the HIV group when compared with the control one. According to Falcão et al., 17 patients classified as having medium or high cardiovascular risk based on the Framingham score were 3.7 times more likely to present atherosclerosis than patients considered at low risk. In another study, patients with subclinical atherosclerosis had higher risk score compared to those with normal to mid-normal thickness. For every 10% increase in the FRS, the odds of having an abnormal CIMT tripled. 18 However, the low number of individuals in the control group indicates another important limitation for our results, whichmay explain the lack of statistical association of carotid thickness and HIV infection. Thus, in later studies, we would need a larger group of individuals to further investigate this hypothesis. Higher mean age was associated with higher CIMT in HIV‑infected and non-infected individuals. Stratified analysis, when controlling for age and CIMT by the infection status, verified that HIV infection does not interfere in the association, that is, the aforementioned relation is independent of the infection status in the analyzed population. However, a larger sample size would be necessary to give greater statistical power to the analysis, considering the wide confidence interval of the raw odds ratios and Mantel–Haenszel odds. When evaluating the association between inflammatory markers and CIMT, a significant association with TNF- α was observed in the multivariate analysis, as the increase in IL1- β levels presented a greater chance of atherosclerosis with p-value close to significance. Ssinabulya et al. 18 found high levels of us-CRP were not associated with CIMT. However, in other studies, higher CIMT was associated with 92