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

Area of Science:

• Immunology
• Metabolomics
• Virology

Background:

• Long-term elite controllers (LTECs) represent a unique subset of individuals with sustained control of HIV, offering insights into functional HIV cure.
• Understanding the metabolic and lipidomic profiles of LTECs, particularly the extreme phenotype (over 10 years of control), is crucial for identifying mechanisms of HIV remission.

Purpose of the Study:

• To investigate the metabolomic and lipidomic signatures associated with long-term HIV control in LTEC-extreme individuals.
• To identify key metabolites and lipid species that differentiate sustained controllers from those who lose control.

Main Methods:

• Plasma samples from LTEC-extreme (n=13), LTEC-losing (n=20), and no-LTEC (n=9) individuals were analyzed using high-resolution mass spectrometry (UHPLC-ESI-qTOF).
• Metabolomics and lipidomics analyses were performed to identify differences in metabolic and lipid profiles.

Main Results:

• Sustained HIV control in LTECs was strongly linked to enhanced tricarboxylic acid (TCA) cycle function.
• Alpha-ketoglutaric acid, a TCA cycle metabolite, was identified as a key factor in persistent HIV control.
• A panel of 45 lipid species effectively differentiated LTEC-extreme from LTEC-losing individuals, suggesting elevated lipid profiles may predict viral replication.

Conclusions:

• Enhanced TCA cycle function and specific metabolites like alpha-ketoglutaric acid are associated with long-term HIV control.
• Lipidomics signatures can potentially predict viral rebound in individuals maintaining long-term HIV control.