HIV is a virus that infects immune cells. It creates reservoirs in secondary lymphoid organs (SLOs), which remain invisible to the immune system. By killing infected cells, HIV induces immunodeficiency and death if left untreated with antiretroviral therapy (ART). It also induces a gut barrier disruption. Gut leakage and killed cells both contribute to the chronic activation of innate immunity. The innate immune system includes the Innate Lymphoid Cells (ILCs) that support mucosal barrier protection. However, HIV promotes an ILC loss in blood and modified functions in SLO-resident ILCs . We do not know whether ILCs suffer from a similar loss in SLOs and the role of these functions. Although HIV chronic inflammation is likely involved in these 2 phenomena, the main triggers as well as the underlying signalling pathways are still unknown. Also, the impact of ART has not been explored yet. By analysing samples from (un)treated HIV patients, this project aims to better characterize ILC depletion in SLOs the epigenomic and transcriptomic signatures of the survival cells, as well as the local pro-inflammatory state. Next, we will integrate these data by bio-informatics analysis to identify triggers of ILC depletion and functions. Finally, we aim to validate these findings in a humanized model and target the triggers in vivo.