HIV-1 infection remains an incurable disease, with the latent virus persisting in the immune cells invisible to therapy and causing viral rebound within days once therapy is stopped Recent new insights show that cells that harbor HIV can divide, by a process called clonal expansion Clonal expansion of cells carrying HIV-1 is considered as being part of the main mechanisms of HIV-1 persistence, with our own data confirming its importance in viral rebound We will revisit the fundamental biology of HIV-1 integration, its impact on cellular expansion, viral rebound and related pathways involved in HIV-1 persistence Only a minute amount of HIV-1+ cells is capable to fuel viral rebound and we will thoroughly characterize these cells, by studying the exact location of HIV-1, function of the gene where HIV-1 integrates, the epigenetic state of the HIV-1 and the surrounding DNA, and the chromatin structure Subsequently, we will redesign the HIV integration landscape by using target integration in easier to study cell lines This cell lines will be in depth characterized To conclude, this project will uncover the pathways and drivers involved in clonal expansion of cells carrying potentially rebounding HIV-1 and will contribute to the search for an HIV-1 cure