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oai:repisalud.isciii.es:20.500.12105/148702025-05-23T14:54:11Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16958col_20.500.12105_16961col_20.500.12105_16977

00925njm 22002777a 4500 dc Masip, Jenifer author Rallón, Norma author Yeregui, Elena author Olona, Montserrat author Resino, Salvador author Benito, José Miguel author Viladés, Consuelo author García-Pardo, Graciano author Alcamí, José author Ruiz-Mateos, Ezequiel author Gómez-Bertomeu, Frederic author Vargas, Montserrat author Navarro, Marta author Oteo, José A author Pineda, Juan A author Martí, Anna author Alba, Verónica author Vidal, Francesc author Peraire, Joaquin author Rull, Anna author ECRIS integrated in the Spanish AIDS Research Network author 2022-04-20 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. Front Immunol. 2022 Apr 20;13:822272. 10.3389/fimmu.2022.822272 1664-3224 Frontiers in Immunology 35514981 http://hdl.handle.net/20.500.12105/14870 HIV infection Kreb's cycle Elite controllers (ECs) Lipidomics Long-term Mass spectrometry Metabolomics Viral Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control