Amino Acid Concentrations in HIV-Infected Youth Compared to Healthy Controls and Associations with CD4 Counts and Inflammation

Abstract

Amino acids play critical roles in metabolism, cell function, body composition and immunity, but little data on plasma amino acid concentrations in HIV are available. We evaluated plasma amino acid concentrations and associations with CD4 counts and inflammatory biomarkers in HIV-infected youth. HIV-infected subjects with a high (≥500 cells/mm) and low (<500 cells/mm) current CD4 T cell counts were compared to one another and to a matched healthy control group. Plasma concentrations of 19 amino acids were determined with an amino acid analyzer. Plasma levels of interleukin-6, tumor necrosis factor receptor-I, and soluble vascular cellular adhesion molecule-I were also measured. Seventy-nine HIV-infected subjects (40 and 39 with high and low CD4 T cell counts, respectively) and 40 controls were included. There were no differences in amino acid concentrations between HIV-infected subjects with high or low CD4 T cell counts. When combined, the HIV-infected group exhibited significantly lower median plasma concentrations compared to controls for total, essential, branched-chain and sulfur amino acids, as well as for 12 individual amino acids. Glutamate was the only amino acid that was higher in the HIV-infected group. There were no significant correlations between amino acid endpoints and inflammatory biomarkers for either HIV-infected group or controls. Plasma amino acid concentrations were lower in HIV-infected youth compared to healthy controls, regardless of immune status, while glutamate concentrations were elevated. These findings can inform future interventional studies designed to improve metabolic and clinical parameters influenced by amino acid nutriture.

Plasma metabolomic study in perinatally HIV-infected children using 1H NMR spectroscopy reveals perturbed metabolites that sustain during therapy

“…A study by Ziegler et al reported decreased levels of plasma amino acids except glutamate in HIV-infected youth [60]. Our study also observed decreased valine, aspartatic acid, glycine, https://doi.org/10.1371/journal.pone.0238316.g003…”

“…A study by Ziegler et al reported decreased levels of plasma amino acids except glutamate in HIV-infected youth [ 60 ]. Our study also observed decreased valine, aspartatic acid, glycine, tyrosine, serine and sarcosine levels in the HIV infected treatment-naïve group.…”

Modulation of Phenylalanine and Tyrosine Metabolism in HIV-1 Infected Patients with Neurocognitive Impairment: Results from a Clinical Trial

“…At baseline, we observed higher fecal Phe/Tyr and similar fecal Phe and Tyr concentrations in HIV positive participants than in healthy controls and this was not surprising, given the fact that in the setting of HIV infection Phe/Tyr is correlated to markers of systemic immune activation [14]. In this context, amino acid status of HIV-1 infected patients significantly differs from that of healthy controls and this could be explained by differences in intestinal absorption, amino acid utilization and requirement and inflammatory biomarkers [25]. Moreover, in HIV positive subjects as well as in negative individuals, phenylalanine and tyrosine represent precursors involved in the synthesis of catecholamines, such as dopamine; Phe/Tyr is usually considered a marker of the activity of tetrahydrobiopterin, the enzyme that catalyzes the first step of the pathway of catecholamines synthesis (the transformation of phenylalanine into tyrosine), therefore an elevated Phe/Tyr has been associated with a reduced level of dopamine [14] and subsequently with imbalanced cognitive abilities.…”

HIV infection and latency induce a unique metabolic signature in human macrophages

“…Currently, only a few reports support a role of glutamine/glutamate as a major source of energy in HIV 71–73 . For instance, two recent independent reports indicated that in the periphery, CD4 + T cell counts were inversely correlated with high serum levels of glutamine and glucose, suggesting a role of these metabolites early on in infection and viral spread 71,74 . Therefore, glutamine becomes an essential metabolite in early stages of HIV infection, but also is essential during the generation and survival of viral reservoirs.…”