Federico de América Perdomo Celis

This symposium summarized evidence supporting a role of immunometabolism in HIV-associated chronic inflammation during antiretroviral therapy (ART). Particularly, four scientist discussed topics related with metabolic reprogramming of CD8 and NK cells, strategies to limit inflammation and T cell hyperactivation, and novel glycomic biomarkers of accelerated biological aging during ART.

Dr. Dimitra Peppa discussed recent findings on strategies to improve the functionality of CD8+ T cells and NK cells by reprogramming metabolism using IL-15 or reinvigorating mitochondrial fitness. Dr. J. Victor Garcia showed that spironolactone, a drug commonly used to treat hypertension and heart failure, suppresses HIV-1 transcription, blocks viral reactivation, and accelerates viral decay in vivo. In addition, spironolactone promotes the decrease of multiple inflammatory genes in several tissues. Dr. Mohamed Abdel-Mohsen discussed that ART-treated HIV infection accelerates premature aging-associated IgG glycomic dysregulations, which are linked to higher inflammation. These IgG glycomic alterations correlate with the incidence of HIV-associated co-morbidities and they may be excellent candidates for biomarker discovery. Finally, modulation of these IgG glycomic alterations can enhance the Fc-mediated anti-viral activity of HIV-specific antibodies. Dr. Yufei Mo presented results of the effect of Nicotinamide mononucleotide (NMN), an anti-aging molecule, on HIV infection in vitro and in vivo. She showed that NMN treatment suppresses HIV infection by decreasing activated CD25+ CD4+ T cells and potentiating CD4 T cell reconstitution.

The data presented further support the key role of immunometabolism on HIV-associated chronic inflammation during ART. Multiple novel strategies are currently being evaluated to promote immune reconstitution and limit the development of comorbidities such as cardiovascular disease, metabolic syndrome, and aging. Combinatorial strategies, such as spironolactone, MNM, or prevention of glycomic dysregulations, could help to enhance the functionality of effector cells such as CD8+ T cells and NK cells, decrease HIV-1 transcription, and limit chronic inflammation. These novel perspectives need to be evaluated in the future in people with HIV receiving ART aiming at the prevention of chronic comorbidities.