Background: Antiretroviral therapy has significantly improved prognosis in treatment against HIV infection, however, prolonged exposure is associated to cardiovascular diseases, lipodystrophy, type 2 diabetes, insulin resistance, metabolic alteration, as obesity which includes the accumulation of oxidative stress in adipose tissue. FGF21 is a peptide hormone that is known to regulate glucose and lipid metabolism. FGF21 is expressed and secreted primarily in the liver and adipose tissue, promoting oxidation of glucose/fatty acids and insulin sensitivity. Alterations in FGF21 may be associated with the development of insulin resistance, metabolic syndrome and cardiovascular disease. We hypothesized that FGF21 protein levels are associated with metabolic abnormalities, placing special attention to the alterations in relation to the concurrence of overweight/obesity in people living with HIV (PLWH). Design: Serum FGF21 was analyzed in 241 subjects, 160 PLWH and 81 unrelated HIV-uninfected subjects as a control group. Clinical records were consulted to obtain CD4+ cell counting and number of viral RNA copies. Serum FGF21 levels were tested for correlation with anthropometric and metabolic parameters; glucose, cholesterol, HDL, LDL, VLDL, triglycerides, insulin and indexes of atherogenesis and insulin resistance (HOMA). Results: The participants were classified into four groups: (i) PLWH with normal weight, (ii) PLWH with overweight/obesity, (iii) HIV-uninfected with normal weight, and (iv) HIV-uninfected with overweight/obesity. Insulin levels were higher in normal-weight PLWH than in the HIV-uninfected group but not statistically significant, however, for the overweight/obesity PLWH group, insulin levels were significantly higher in comparison with the other three groups (p<0.0001). For FGF21, serum levels were slightly higher in the overweight/obesity groups in both patients and controls. In HIV-infected subjects, FGF21 levels showed a strong positive correlation with triglycerides, insulin levels and insulin resistance with a p-value <0.0001. In the seronegative group, FGF21 was only correlated with weight and waist circumference, showing an important association of FGF21 levels with the degree of obesity of the individuals. Conclusion: Insulin resistance and FGF21 elevations were observed in overweight-obese PLWH. FGF21 elevation could be viewed as a compensation mechanism as, in the control group, FGF21 correlations appeared to be confined to weight and waist circumference. This can be explained based on the action of FGF21 promoting the uptake of glucose in adipose tissue. In PLWH, FGF21 was low, possibly as a result of a change in adiposity leading to a metabolic disruption.

Combined antiretroviral therapy has improved quality and life expectancy of people living with human immunodeficiency virus (HIV). However, this therapy increases oxidative stress (OS), which in turn causes alterations in lipid and carbon metabolism, kidney disease, liver cirrhosis, and increased risk of cardiovascular disease. The Klotho gene has been implicated in cardiovascular risk increase. Klotho protein expression at X level decreases the risk of heart disease. HIV-positive people usually present low plasma levels of Klotho; thus, contributing to some extent to an increase in cardiovascular risk for these types of patients, mostly by favoring atherosclerosis. Therefore, our aim is to provide an overview of the effect of OS on Klotho protein and its consequent cardiometabolic alterations in HIV-positive patients on antiretroviral therapy.

To examine potential risk factors associated with biochemical alterations in renal function in a population diagnosed with HIV/AIDS undergoing antiretroviral treatment. This is an observational, transversal, and relational design study that included 179 HIV-seropositive subjects. Glucose serum, cholesterol, triglycerides, total proteins, albumin, creatine, urea, blood urea nitrogen (BUN), and electrolytes levels were determined for each individual. Renal function was evaluated through the glomerular filtration rate (GFR), using the CKD-EPI equation. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m². Univariate model significant variables, with a 95% confidence interval (CI), were included in a multivariate logistic regression analysis. CKD prevalence in patients was 7.3%, with comorbidities of 7.8% for type 2 diabetes mellitus, 7.3% for arterial hypertension, and 35.2% for dyslipidemia. Additionally, both hypernatremia and hypophosphatemia were detected in 57% (n = 102) of the patients. Multivariate logistic regression suggested that CD4+ T cell count < 200 (P = .02; OR 0.2; CI 95% 0.08–0.8) was associated to hyponatremia; similarly, detectable viral load was associated to hypokalemia (P = .02; OR 5.1; CI 95% 1.2–21.3), hypocalcemia (P = .01; OR 4.1; CI 95% 1.3–12.3), and hypermagnesemia (OR 3.9; CI 95% 1.1–13.6). Patient age was associated to both hypophosphatemia (P = .01; OR 2.4; CI 95% 1.1–5.0) and hypermagnesemia (P = .01; OR 2.8; IC 95% 1.1–7.0), and high creatinine levels were associated to nucleoside reverse transcriptase inhibitor treatment (P = .001; OR 42.5; CI 95% 2.2–806.9). Lastly, high BUN levels were associated to age (P = .03; OR 3.8; CI 95% 1.0–14.4), while GFR 60 to 89 mL/min/1.73 m² was associated to dyslipidemia (P = .02; OR 2.2; CI 95% 1.1–4.5). CD4+ T cell and viral load were the main factors associated with renal biochemical alterations.

Background: In cancer, an effective immune response involves the action of several different cell types, among which CD8 T cells play a major role as they can specifically recognize and kill cancer cells via the release of cytotoxic molecules and cytokines, being of major importance for adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs). The inflammation resulting from the tumor growth attracts both activated and bystander T cells. For an effective antitumor response, the T cell must express a specific group of chemokine receptors and integrins which include CD103, CD39, CD69, and CD25. These markers had already been analyzed in various cancers, not including breast cancer and their subsequent subtypes, until now. To analyze, the key receptors on ex vivo expanded tumor-infiltrating lymphocytes in luminal A and luminal B breast cancer (BC) subtypes. Materials and Methods: We were successful in expanding TILs ex vivo using a standard TIL culture condition from a cohort study of 15 primary luminal A and luminal B breast cancer patients. Furthermore, we examined the expression of CD103, CD39, CD69, and CD25 biomarkers after the expansion by flow cytometry. Results: We found that the information about the percentage of TILs obtainable after the ex vivo expansion is not associated to nor it is dependent on the heterogeneity of the TIL population before the expansion and does not differ by the molecular subtype (p>0.05). We also found that there is a major population of memory-resident antitumor CD8+CD103+CD39+ and CD8+CD103+ CD69+ TILs present in the stroma after the expansion when compared to CD4 immunosubtypes (p< 0.0001). Only the CD8+CD103+CD39+ subpopulation was related to BC subtype (0.0009). Conclusion: Evidence from our study suggests that CD8 TILs present in the stroma of luminal A and luminal B breast cancer patients can be quantified and phenotyped by flow cytometry and be further expanded ex vivo. The immuno-phenotyping of these markers may be targeted to improve the success of immunotherapeutic approaches, such as adoptive cellular therapy (ACT) in patients with BC.

Metabolic alterations, resulting from factors such as obesity or infections (HIV), generate inflammation in the body, affecting the immune system and causing oxidative stress. Prolonged exposure to antiretroviral therapy (ART) conditions the appearance of alterations considered risk factors for metabolic syndrome (MetS), affecting the quality of life in people living with HIV/AIDS (PLWHA). β-klotho is a protein that can counteract levels of oxidative stress. The aim was to determine the relation of β-klotho and oxidative stress with metabolic alterations in PLWHA. We hypothesized that levels of β-klotho and malondialdehyde (MDA) are related in PLWHA on ART with overweight/obesity. As a result of comparing cases versus controls, significant differences were obtained in levels of β-klotho (p = 0.011), MDA (p < 0.0001), body mass index (p = 0.001), and weight (p < 0.0001). The presence of MetS in PLWHA was 21.2% and 10.6% according to the World Health Organization and ATP III (National Cholesterol Education Program Adult Treatment Panel III) criteria, respectively. The founded correlations were of β-klotho (r = 0.019) and MDA (r = 0.0001), both with CD4+ cells in PLWHA. In controls, β-klotho was correlated with very low-density lipoprotein (r = 0.035) and atherogenic index (AI; r = 0.037), MDA with AI (r = 0.039), cholesterol, and low-density lipoprotein (r = 0.002). The increase of inflammation in the organism, owing to HIV infection and/or the presence of obesity, conditions metabolic disruption or depletion of elements needed for homeostasis in the human body.

Objective: The aim of this study was to determine risk factors that increase cardiovascular risk and to estimate the cardiovascular risk at 5 and 10 years in overweight/obese in seropositive subjects undergoing cART from the of Northern Mexico Methods: This study included 186 PLWH under cART. The variables analyzed were were CD4+ count, viral load, lipid profile, glucose, insulin resistance, anthropometric measures, family history of hypertension and cardiovascular disease, years of treatment and cART scheme. In this study we analyzed the probable estimate of cardiovascular risk using the algorithmic models D: A: D (5-year period) and Framingham (10-year period). Results: In our study, 51.3% of the PLWH had arterial hypertension; most of the subjects were diagnosed with overweight, hypertriglyceridemia and metabolic syndrome, which are factors that increase the risk of cardiovascular disease. The evaluation of cardiovascular risk with the Framingham model, it is low and with the D model: A: D is moderate Conclusions: PLWH receiving cART present factors that potentiate the risk of early heart disease which are hypercholesterolemia, hypertriglyceridemia, smoking and age. The cardiovascular risk with the algorithmic models D: A:D and Framingham are low to moderate; however these latter results should be taken with caution since the study population is a young population, which will not allow us to establish an accurate cardiovascular risk. It is important to take into account other factors such as overweight or obesity, smoking or coinfections, in addition to years of exposure to cART, which could increase the rate of heart disease.