Immune Activation as a Cause of Insulin Resistance in Adults Living With HIV-1 on Effective Antiretroviral Therapy

Overview

The aim of this study is to characterize in non-viremic HIV-1 patients under antiretroviral therapy an immune activation profile that the investigators have previously shown to be strongly linked to hyperinsulinemia. This characterization will be carried out via 3 different approaches. First, the investigators will analyze the metabolites present in the plasma of patients presenting with the profile of interest. Second, the investigators will study the transcriptome of the peripheral blood mononuclear cells of these patients. Finally, the investigators will search whether some factors released by these cells are able to induce insulin resistance. In addition the ability of the profile of interest to predict an increase in insulinemia over time will be assessed.

The working hypothesis of this study is that in efficiently treated HIV patients, various profiles of immune activation may be distinguished, each favouring particular comorbidities. Using a panel of 68 soluble and cell surface markers, the investigators have previously measured the level of activation in circulating Cluster of Differentiation 4+ (CD4+) and Cluster of Differentiation 8+ (CD8+), T cells, B cells, monocytes, Natural Killers (NK) cells, neutrophils, and endothelial cells as well as of inflammation and fibrinolysis in 120 virologic responders over 45 years of age. Two independent hierarchical clustering analyses allowed the investigators to identify five patient groups, each with the same activation profile. One of these profiles, Profile#2, was strongly associated with hyperinsulinemia (Psomas et al., 2016). The main objective of the present study is to better define Profile#2. To this aim, the investigators will analyze by mass spectrometry the metabolites in the plasma of patients with various profiles including the one of interest. Concurrently, the investigators will perform an RiboNucleic Acid Sequencing (RNASeq) analysis on peripheral blood mononuclear cells (PBMC) from the same patients. These metabolomic and transcriptomic data will help to better define the immune activation profiles. The secondary objective is to test whether the link the investigators have observed between Profile#2 and insulin resistance is causative. To this aim, by following over time patients' insulinemia, the investigators will test whether Profile#2 is predictive of an increase in insulinemia. The investigators will also look for factors released by PBMC of patients with Profile#2 able to induce insulin resistance.