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However, the impact of immune aging on the effectiveness of such protective alleles remains unclear. In this study, we assessed SIVmac239 replication in aged (17\u201323\u2009yr old) rhesus macaques (RMs) exhibiting low frequencies of na\u00efve T cells and expanded effector memory T cells, that were further stratified by the presence (MHC\u207a) or absence (MHC\u2212) of 3 known \u201cprotective MHC-Ia alleles\u201d (Mamu-A*01, Mamu-B*08, or Mamu-B*17). All RMs were infected with SIVmac239 and viral dynamics monitored longitudinally. MHC\u207a RMs demonstrated significantly lower plasma viral loads (PVLs) through 70\u2009d postinfection compared with MHC\u2212 RMs. At 70 d postinfection, half of the RMs from each group initiated suppressive triple antiretroviral therapy comprising dolutegravir, emtricitabine, and tenofovir disoproxil fumarate (TDF) for 15\u2009wk, followed by suboptimal TDF monotherapy for an additional 21\u2009wk. While antiretroviral therapy substantially reduced PVL in both groups, viral decline was accelerated in MHC\u207a RMs relative to MHC\u2212 RMs. Moreover, upon switching to TDF monotherapy, PVL rebounded by almost 3 logs in MHC\u2212 RMs, while MHC\u207a RMs maintained viral suppression. Collectively, these findings indicate that protective MHC-Ia alleles can mediate viral control in aged hosts, even under suboptimal treatment conditions, and highlight the potential role of optimized CD8+ T cell responses in strategies targeting viral persistence in aging populations.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag272","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:56:00Z","timestamp":1792461360000},"source":"Crossref","is-referenced-by-count":0,"title":["Preservation of MHC-Ia protective allele suppression of SIVmac239 in aged rhesus macaques"],"prefix":"10.1093","volume":"215","author":[{"given":"Alejandra","family":"Marenco","sequence":"first","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR,","place":["United States"]},{"name":"Oregon National Primate Research Center, Oregon Health and Science University , Beaverton, OR,","place":["United 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