RT Journal Article
T1 Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control.
A1 Masip, Jenifer
A1 Rallón, Norma
A1 Yeregui, Elena
A1 Olona, Montserrat
A1 Resino, Salvador
A1 Benito, José M
A1 Viladés, Consuelo
A1 García-Pardo, Graciano
A1 Alcamí, José
A1 Ruiz-Mateos, Ezequiel
A1 Gómez-Bertomeu, Frederic
A1 Vargas, Montserrat
A1 Navarro, Marta
A1 Oteo, José A
A1 Pineda, Juan A
A1 Martí, Anna
A1 Alba, Verónica
A1 Vidal, Francesc
A1 Peraire, Joaquin
A1 Rull, Anna
K1 HIV infection
K1 Kreb's cycle
K1 elite controllers (ECs)
K1 lipidomics
K1 long-term
K1 mass spectrometry
K1 metabolomics
K1 viral
AB 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.
YR 2022
FD 2022-04-20
LK http://hdl.handle.net/10668/20579
UL http://hdl.handle.net/10668/20579
LA en
DS RISalud
RD Apr 8, 2025