title: Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.
abstract: We 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.
  
  
  
  Twenty-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.
  
  
  
  Blood-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.
authors.affiliation: Federal University of Sao Paulo, Department of Medicine, Sao Paulo-SP, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Scarpellini
authors.affiliation: Federal University of Sao Paulo, Department of Medicine, Sao Paulo-SP, Brazil.
authors.forename: Michelle
authors.initials: M
authors.lastname: Zanoni
authors.affiliation: Federal University of Sao Paulo, Department of Medicine, Sao Paulo-SP, Brazil.
authors.forename: Maria Cecilia Araripe
authors.initials: MC
authors.lastname: Sucupira
authors.affiliation: University of California at San Francisco, Department of Medicine, San Francisco, CA, United States of America.
authors.forename: Hong-Ha M
authors.initials: HM
authors.lastname: Truong
authors.affiliation: Federal University of Sao Paulo, Department of Medicine, Sao Paulo-SP, Brazil.|Federal University of Sao Paulo, Department of Microbiology, Sao Paulo-SP, Brazil.
authors.forename: Luiz Mario Ramos
authors.initials: LM
authors.lastname: Janini
authors.affiliation: Federal University of Sao Paulo, Department of Medicine, Sao Paulo-SP, Brazil.
authors.forename: Ismael Dale Cotrin
authors.initials: ID
authors.lastname: Segurado
authors.affiliation: Federal University of Sao Paulo, Department of Medicine, Sao Paulo-SP, Brazil.
authors.forename: Ricardo Sobhie
authors.initials: RS
authors.lastname: Diaz