Abdominal Adipose Tissue Is Associated With Alterations in Tryptophan-Kynurenine Metabolism and Markers of Systemic Inflammation in People With Human Immunodeficiency Virus

Background: While both adipose tissue accumulation and tryptophan metabolism alterations are features of HIV infection, their interplay is unclear. We investigated associations between abdominal adipose tissue, alterations in kynurenine pathway of tryptophan metabolism, and systemic inflammation in people with HIV (PWH). / Methods: 864 PWH and 75 uninfected controls were included. Plasma samples were collected and analyzed for kynurenine metabolites, neopterin, high-sensitivity CRP (hs-CRP), lipids. Regression models were used to test associations in PWH. / Results: PWH had higher kynurenine-to-tryptophan ratio than uninfected individuals (p-value < 0.001). In PWH, increase in waist-to-hip ratio was associated with higher kynurenine-to-tryptophan ratio (p-value 0.009) and quinolinic-to-kynurenic acid ratio (p-value 0.006) and lower kynurenic acid concentration (p-value 0.019). Quinolinic-to-kynurenic acid ratio was associated with higher hs-CRP (p-value < 0.001) and neopterin concentrations (p-value <0.001), while kynurenic acid was associated with lower hs-CRP (p-value 0.025) and neopterin concentrations (p-value 0.034). / Conclusion: In PWH increase in abdominal adipose tissue was associated with increased quinolinic-to-kynurenic acid ratio, suggesting activation of pro-inflammatory pathway of kynurenine metabolism, with reduction of anti-inflammatory molecules, and increase in systemic inflammation. Our results suggest dysregulation of kynurenine metabolism associated with abdominal fat accumulation to be a potential source of inflammation in HIV infection

Long-lasting alterations in adipose tissue density and adiponectin production in people living with HIV after thymidine analogues exposure

BACKGROUND: Thymidine analogues (TA) and didanosine (ddI) are associated with long-lasting adipose tissue redistribution. Adiponectin is a widely used marker of adipocyte activity, and adipose tissue density assessed by CT-scan is associated with adipocyte size and function. We hypothesized that prior exposure to TA and ddI was associated with long-lasting adipose tissue dysfunction in people living with HIV (PLWH). Thus, we tested possible associations between markers of adipose tissue dysfunction (adipose tissue density and adiponectin) and prior exposure to TA and/or ddI, years after treatment discontinuation. METHODS: Eight hundred forty-eight PLWH from the COCOMO study were included and stratified according to prior exposure to TA and/or ddI (with, n = 451; without n = 397). Visceral (VAT) and subcutaneous (SAT) adipose tissue area and density were determined by single slice abdominal CT-scan at lumbar 4th level. Venous blood was collected and analyzed for adiponectin. Multivariable linear and logistic regression analyses were used to test our hypotheses. Multivariable models were adjusted for age, sex, smoking, origin, physical activity, BMI, and adipose tissue area (VAT or SAT area, accordingly to the outcome). RESULTS: prior exposure to TA and/or ddI was associated with excess risk of low VAT (adjusted OR (aOR) 1.74 [1.14; 2.67]) and SAT density (aOR 1.74 [1.18; 2.58]), for a given VAT and SAT area, respectively. No association between VAT and SAT density with time since TA and/or ddI discontinuation was found. 10 HU increase in VAT density was associated with higher adiponectin plasma level and this association was not modified by prior exposure to TA and/or ddI. Prior exposure to TA and/or ddI was associated with 9% lower [- 17;-2] plasma adiponectin levels and with excess risk of low adiponectin (aOR 1.74 [1.10; 2.76]). CONCLUSIONS: We described low adipose tissue density and impaired adiponectin production to be associated with prior exposure to TA and/or ddI even years after treatment discontinuation and independently of adipose tissue area. These findings suggest that prior TA and ddI exposure may have long-lasting detrimental effects on adipose tissue function and, consequently, on cardiometabolic health in PLWH

Prevalence and risk factors of prolonged QT interval and electrocardiographic abnormalities in persons living with HIV

OBJECTIVE: Abnormal electrocardiograms (ECG) are associated with increased risk of arrhythmias and sudden cardiac death. We aimed to investigate the prevalence and associated risk factors of prolonged QTc and major ECG abnormalities, in persons living with HIV (PLWH) and uninfected controls. DESIGN: PLWH aged ≥40 were recruited from the Copenhagen comorbidity in HIV infection (COCOMO) study and matched on sex and age to uninfected controls from the Copenhagen General Population Study. METHODS: ECGs were categorized according to Minnesota Code Manual of ECG Findings definition of major abnormalities. A QT interval corrected for heart rate (QTc) >440ms in males and >460ms in females was considered prolonged. Pathologic Q-waves were defined as presence of major Q-wave abnormalities. RESULTS: ECGs were available for 745 PLWH and 2,977 controls. Prolonged QTc was prevalent in 9% of PLWH and 6% of controls, p = .052. Pathologic Q-waves were more common in PLWH (6%) than in controls (4%), p = .028. There was no difference in prevalence of major ECG abnormalities between PLWH and controls, p = .987.In adjusted analyses, HIV was associated with a 3.6ms[1.8-5.4] longer QTc interval, p < .001, and HIV was independently associated with prolonged QTc (adjusted odds ratio: 1.59 [1.14-2.19]), p = .005. HIV was borderline associated to pathologic Q-waves after adjusting, p = .051. CONCLUSION: HIV was associated with higher odds ratio of prolonged QTc after adjustment for cardiovascular risk factors, but analyses were not adjusted for QT-prolonging medication. Although evidence indicated more pathologic Q-waves in PLWH, the risk seemed to be associated mainly with an adverse risk profile