Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment

Abstract

BackgroundWe evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment.ResultsTwenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine‐1‐phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected.ConclusionsBlood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

Metabolite changes in blood predict the onset of tuberculosis

“…It is unknown to what extent the presence of opportunistic infections and the perturbed immune responses associated with HIV infection will alter the predictive signatures. However, previous studies show hardly any overlap between the TB and HIV metabolic profiles 23 , 24 , with plasma glutamate being the only biomarker common for both TB and HIV 24 .…”

Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses

“…Elevated triglycerides have also consistently been reported with bacterial [ 11 , 12 , 13 ] and parasitic infections [ 14 , 15 ]. Altered sphingomyelin metabolism has also been reported, with increases in pneumonia patients [ 37 ] and decreases in HIV patients [ 38 ].…”

“…In our study, sphingomyelins were increased only in the serum of vaccinated horses. Sphingomyelin levels have previously been shown to be elevated in patients with pneumonia [ 37 ], and melioidosis [ 53 ] while they are unaltered in several bacteremic conditions [ 53 ] and decreased in AIDS patients [ 38 ]. Our data indicate that the immune response induced by vaccination has a more dramatic effect than leptospiral infection on sphingomyelin synthesis in horses.…”

Persistent metabolic changes in HIV-infected patients during the first year of combination antiretroviral therapy

“…Hypertriglyceridemia was identified as one of the first metabolic consequences of HIV infection 6 . Since then, studies using Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) applied to biofluids of HIV-infected individuals have confirmed the presence of HIV induced metabolic alterations 1 , 7 – 9 . Investigating in vitro models of HIV infection using primary macrophages and CD4 + T-cells had different metabolic outcomes during HIV infection.…”