CD8⁺ T cells from natural controllers consist of a high frequency of functional, long-lived memory HIV-specific cells expressing TCF-1 at high levels, whereas those from noncontrollers on ART consist of a low frequency of HIV-specific cells that express low or intermediate levels of TCF-1 and exhibit residual dysfunction. Treatment with the GSK-3 inhibitor BIO for 12 hours increased the expression of TCF-1 in these cells. Short-term GSK-3 inhibition of HIV-specific CD8⁺ T cells in noncontrollers improves their metabolic fitness, survival capacity, homeostatic proliferation, and antiviral capacity, although these features might still be less prominent than those in natural controllers. Reprogramming HIV-specific CD8⁺ T cells by GSK-3 inhibition to increase stemness may allow for more efficient immune boosting, resulting in a higher number of HIV-specific CD8⁺ T cells with enhanced survival and antiviral capacities to help control the virus after treatment interruption.