Grant: Project Grant

In people living with HIV (PLWH) receiving antiretroviral therapy (ART), inflammation and changes in cellular metabolism (glucose and lipids) remain associated with increased risk of cardiovascular diseases and cancer. Even after decades of ART, immunity against HIV remains unable to control viral replication upon ART discontinuation. Immunometabolism controls the quality of the metabolism and immune response against viruses. Therefore, strategies to control inflammation and improve cellular metabolism to enhance immunity against HIV are research priorities. In the blood, the elevation of acyl coA binding protein (ACBP) acts as a metabolic checkpoint by decreasing both cellular components recycling (autophagy) and mitochondrial cell respiration (energy factory). High levels of ACBP are associated with cardiovascular diseases, aging, and viral infections. We are the first to have observed high levels of ACBP in the blood of hospitalized COVID-19 patients and in PLWH on ART. We propose to study in the laboratory the role of ACBP in different groups of PLWH with or without ART, in blood samples already collected from participants and available in our biobanks. Specifically, we will assess: 1) The factors associated with high ACBP in blood such as age, sex at birth, timing of ART initiation and type of ART, cardiovascular risk, inflammation markers, glucose and lipid profiles, measured in the early to the chronic phase of the HIV infection. 2)The effect of ACBP on cellular metabolism, inflammation and the response against HIV. In an exploratory objective, we will identify the cellular receptors of ACBP on immune cells. 3)The effect of ACBP on HIV-infected T-cells and macrophages in the presence of ART. Study findings will help designing strategies to target ACBP, improve metabolism and unleash immune function to better fight HIV in ART-treated PLWH. In combination with other strategies, ACBP therapeutic intervention may contribute to the HIV cure agenda.