CD4 and HIV-1 infection: Progressive depletion and anergy of CD4+ T cells and increased systemic immune activation are hallmarks of HIV-1 infection and pathogenesis.[61] During the chronic infection, the loss of CD4+ T cells can be partially reversed by antiretroviral treatment but a complete restoration is never achieved.[62] Apoptosis mostly occur in bystander non-infected cells[4] but HIV-1 has developed mechanisms to avoid the induction of apoptosis in the infected cells in order to assure viral production and persistence.