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| Pàgina inicial > Articles > Articles publicats > Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control |
(Hospital Universitari Joan XXIII de Tarragona) (Hospital Universitario Rey Juan Carlos (Madrid)) (Hospital Universitari Joan XXIII de Tarragona) (Instituto de Salud Carlos III) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Universidad de Sevilla) (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT)) (Unidad de Investigación Hospital Universitario de Valme) (Instituto de Salud Carlos III) (Instituto de Salud Carlos III)| Data: | 2022 |
| Resum: | 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. |
| Ajuts: | Instituto de Salud Carlos III PI19/00004 Instituto de Salud Carlos III PI19/01127 Instituto de Salud Carlos III PI19/01337 Instituto de Salud Carlos III PI19/00973 Instituto de Salud Carlos III PI20/00326 Ministerio de Economía y Competitividad RD16/0025/0006 Ministerio de Economía y Competitividad RD16/0025/0013 Ministerio de Economía y Competitividad RD16/0025/0020 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Elite controllers (ECs) ; HIV infection ; Kreb's cycle ; Lipidomics ; Long-term ; Mass spectrometry ; Metabolomics ; Viral |
| Publicat a: | Frontiers in immunology, Vol. 13 (april 2022) , ISSN 1664-3224 |
