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Immunotherapy could potentially be applied to eradicate reactivated HIV-1 in latently infected CD4<jats:sup>+<\/jats:sup> T lymphocytes. Although the existence of HIV-1-specific CD8<jats:sup>+<\/jats:sup> T memory stem cells (T<jats:sub>SCM<\/jats:sub>s) is well established, there are currently no reports regarding methods using CD8<jats:sup>+<\/jats:sup> T<jats:sub>SCM<\/jats:sub>s to treat HIV-1 infection. In this study, we quantified peripheral blood antigen-specific CD8<jats:sup>+<\/jats:sup> T<jats:sub>SCM<\/jats:sub>s and then expanded HIV-1-specific T<jats:sub>SCM<\/jats:sub>s that targeted optimal antigen epitopes (SL9, IL9, and TL9) in the presence of interleukin- (IL-) 21 or IL-15. The suppressive capacity of the expanded CD8<jats:sup>+<\/jats:sup> T<jats:sub>SCM<\/jats:sub>s on HIV-1 production was measured by assessing cell-associated viral RNA and performing viral outgrowth assays. 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