Frontiers in Immunology (Apr 2022)

Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control

  • Jenifer Masip,
  • Jenifer Masip,
  • Jenifer Masip,
  • Norma Rallón,
  • Norma Rallón,
  • Elena Yeregui,
  • Elena Yeregui,
  • Montserrat Olona,
  • Montserrat Olona,
  • Montserrat Olona,
  • Salvador Resino,
  • Salvador Resino,
  • José M. Benito,
  • José M. Benito,
  • Consuelo Viladés,
  • Consuelo Viladés,
  • Consuelo Viladés,
  • Consuelo Viladés,
  • Graciano García-Pardo,
  • Graciano García-Pardo,
  • Graciano García-Pardo,
  • José Alcamí,
  • José Alcamí,
  • José Alcamí,
  • Ezequiel Ruiz-Mateos,
  • Frederic Gómez-Bertomeu,
  • Frederic Gómez-Bertomeu,
  • Montserrat Vargas,
  • Montserrat Vargas,
  • Marta Navarro,
  • José A. Oteo,
  • Juan A. Pineda,
  • Anna Martí,
  • Anna Martí,
  • Anna Martí,
  • Verónica Alba,
  • Verónica Alba,
  • Verónica Alba,
  • Francesc Vidal,
  • Francesc Vidal,
  • Francesc Vidal,
  • Francesc Vidal,
  • Joaquin Peraire,
  • Joaquin Peraire,
  • Joaquin Peraire,
  • Joaquin Peraire,
  • Anna Rull,
  • Anna Rull,
  • Anna Rull,
  • Anna Rull

DOI
https://doi.org/10.3389/fimmu.2022.822272
Journal volume & issue
Vol. 13

Abstract

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Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidomics signatures in the LTEC-extreme phenotype, LTECs with more than 10 years of viral and immunological HIV control, could be pivotal to finding the keys for functional HIV remission. Metabolomics and lipidomics analyses were performed using high-resolution mass spectrometry (ultra-high-performance liquid chromatography–electrospray ionization–quadrupole time of flight [UHPLC-(ESI) qTOF] in plasma samples of 13 patients defined as LTEC-extreme, a group of 20 LTECs that lost viral and/or immunological control during the follow-up study (LTEC-losing) and 9 EC patients with short-term viral and immunological control (less than 5 years; no-LTEC patients). Long-term viral and immunological HIV-1 control was found to be strongly associated with elevated tricarboxylic acid (TCA) cycle function. Interestingly, of the nine metabolites identified in the TCA cycle, α-ketoglutaric acid (p = 0.004), a metabolite implicated in the activation of the mTOR complex, a modulator of HIV latency and regulator of several biological processes, was found to be a key metabolite in the persistent control. On the other hand, a lipidomics panel combining 45 lipid species showed an optimal percentage of separation and an ability to differentiate LTEC-extreme from LTEC-losing, revealing that an elevated lipidomics plasma profile could be a predictive factor for the reignition of viral replication in LTEC individuals.

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