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However, no studies have yet reported on T-cell responses to large numbers of well-characterized HIV-1 epitopes before and under cART within the same individuals. Therefore, how cART affects the maintenance of HIV-1-specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells and which HIV-1-specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells would be useful for curative treatment remain unclear. We investigated T-cell responses to 63 HIV-1 epitopes at pre-cART and under cART in 90 PLWH who received long-term cART. The frequency of T-cell responses to HIV-1 epitopes under long-term cART varied from 0% to 100%, indicating an epitope-dependent effect of long-term cART on HIV-1-specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells. The magnitude of the responses under cART was 26.2% of that at pre-cART. The frequency of T-cell responses to protective epitopes under cART was higher than that to non-protective ones. T-cell responses to HIV-1 epitopes were detected at pre-cART in most non-AIDS HIV patients, whereas they were not detectable at pre-cART in half of the AIDS patients. Long-term cART enhanced the ability of HIV-1-specific T cells to proliferate\n            <jats:italic>in vitro<\/jats:italic>\n            in non-AIDS HIV patients, while it restored this ability of the T cells in AIDS patients. This study demonstrated that CD8\n            <jats:sup>+<\/jats:sup>\n            T cells specific for large numbers of HIV-1 epitopes were maintained in an epitope-dependent fashion under long-term cART and implied that some HIV-1-specific T cells are still candidates as effector cells for curative treatment.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              HIV-1-specific CD8\n              <jats:sup>+<\/jats:sup>\n              T cells are anticipated to become effector cells for curative treatment using the \u201cshock and kill\u201d approach in people living with HIV-1 (PLWH) under combined antiretroviral therapy (cART). Previous studies demonstrated that the frequency of HIV-1-specific CD8\n              <jats:sup>+<\/jats:sup>\n              T cells is reduced under cART and their functional ability remains impaired. These studies analyzed T-cell responses to a small number of HIV-1 epitopes or overlapping HIV-1 peptides. Therefore, the features of CD8\n              <jats:sup>+<\/jats:sup>\n              T cells specific for HIV-1 epitopes under cART remain only partially clarified. Here, we analyzed CD8\n              <jats:sup>+<\/jats:sup>\n              T cells specific for 63 well-characterized epitopes in 90 PLWH. We demonstrated that CD8\n              <jats:sup>+<\/jats:sup>\n              T cells specific for large numbers of HIV-1 epitopes were maintained in an epitope-dependent fashion under long-term cART and that long-term cART enhanced or restored the ability of HIV-1-specific T cells to proliferate\n              <jats:italic>in vitro<\/jats:italic>\n              . This study implies that some HIV-1-specific T cells would be useful as effector cells for curative treatment.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01024-23","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T13:03:21Z","timestamp":1698239001000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Epitope-dependent effect of long-term cART on maintenance and recovery of HIV-1-specific CD8\n            <sup>+<\/sup>\n            T cells"],"prefix":"10.1128","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3852-2288","authenticated-orcid":false,"given":"Nozomi","family":"Kuse","sequence":"first","affiliation":[{"name":"Division of International Collaboration Research and Tokyo Joint Laboratory, Department of Frontier Research, Joint Research Center for Human Retrovirus Infection, Kumamoto University , Kumamoto, 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University , Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Oka","sequence":"additional","affiliation":[{"name":"AIDS Clinical Center, National Center for Global Health and Medicine , Shinjuku-ku, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-6442","authenticated-orcid":false,"given":"Masafumi","family":"Takiguchi","sequence":"additional","affiliation":[{"name":"Division of International Collaboration Research and Tokyo Joint Laboratory, Department of Frontier Research, Joint Research Center for Human Retrovirus Infection, Kumamoto University , Kumamoto, 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