In conjunction with the restricted expression of ICs, which is being heavily investigated to reverse the deficiency of antiviral CD8+ T cells to adequately control HIV-1 infection and eliminate latently infected cells, our data underscore the pivotal role of functional T-cell autophagy to rejuvenate CD4+ and CD8+ T cellular responses, contribute to the recovery of the T-cell compartment by inducing naïve T-cell generation and revamp immune responsiveness in chronic HIV-1 infection. This evidence concerns the gene CD4 and HIV-1 infection.