Abstract
BackgroundPerinatally HIV-infected children on anti-retroviral treatment (ART) are reported to have metabolic abnormalities such as dyslipidemia, lipodystrophy, and insulin resistance which potentially increase the risk of diabetes, kidney, liver and cardiovascular disease.ObjectiveTo elucidate HIV-mediated metabolic complications that sustain even during ART in perinatally HIV-infected children.MethodWe have carried out metabolic profiling of the plasma of treatment-naïve and ART-suppressed perinatally HIV-infected children and uninfected controls using 1H nuclear magnetic resonance (NMR) spectroscopy followed by statistical analysis and annotation.ResultValidated multivariate analysis showed clear distinction among our study groups. Our results showed elevated levels of lactate, glucose, phosphoenolpyruvic acid, propionic acid, 2-ketobutyric acid and tricarboxylic acid (TCA) cycle metabolites in untreated HIV-infected children compared to uninfected controls. ART normalized the levels of several metabolites, however the level of lactate, phosphoenolpyruvic acid, oxoglutaric acid, oxaloacetic acid, myoinositol and glutamine remained upregulated despite ART in HIV-infected children. Pathway analysis revealed perturbed propanoate metabolism, amino acid metabolism, glycolysis and TCA cycle in untreated and ART-suppressed HIV-infected children.ConclusionDeveloping therapeutic strategies targeting metabolic abnormalities may be beneficial for preventing diabetes, cardiovascular disease or other associated complications in perinatally HIV-infected children.
Highlights
According to UNAIDS report 2019, there are approximately 1.7 million children less than 15 years old living with HIV worldwide and 160000 children became newly infected [1]
Our results showed elevated levels of lactate, glucose, phosphoenolpyruvic acid, propionic acid, 2-ketobutyric acid and tricarboxylic acid (TCA) cycle metabolites in untreated HIV-infected children compared to uninfected controls
Developing therapeutic strategies targeting metabolic abnormalities may be beneficial for preventing diabetes, cardiovascular disease or other associated complications in perinatally HIV-infected children
Summary
According to UNAIDS report 2019, there are approximately 1.7 million children less than 15 years old living with HIV worldwide and 160000 children became newly infected [1]. With an expanded life span, HIV-infected children have high prevalence of metabolic abnormalities such as dyslipidemia, lipodystrophy and insulin resistance, which potentially increases the risk of early cardiovascular atherosclerosis, kidney failure, and diabetes in this population [4, 5]. In HIV-infected children, increased use of ART reported to cause dyslipidemia and insulin resistance [12, 13]. Metabolic abnormalities in perinatally HIV-infected children are of great concern since ART is given early in life. A recent study showed increased cardiovascular abnormalities in HIVinfected children without ART(treatment-naïve) [6]. HIV-infected children on anti-retroviral treatment (ART) are reported to have metabolic abnormalities such as dyslipidemia, lipodystrophy, and insulin resistance which potentially increase the risk of diabetes, kidney, liver and cardiovascular disease
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