{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:59:29Z","timestamp":1790269169848,"version":"4.1.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["\u2022\tUM1AI164566"],"award-info":[{"award-number":["\u2022\tUM1AI164566"]}]},{"name":"National Institutes of Health","award":["P30AI050409"],"award-info":[{"award-number":["P30AI050409"]}]},{"name":"National Institutes of Health","award":["\u2022\tRR000165\/OD011132"],"award-info":[{"award-number":["\u2022\tRR000165\/OD011132"]}]},{"name":"National Institutes of Health","award":["OD011023"],"award-info":[{"award-number":["OD011023"]}]},{"name":"National Institutes of Health","award":["\u2022\tP30AI050410"],"award-info":[{"award-number":["\u2022\tP30AI050410"]}]},{"name":"National Institutes of Health","award":["\u2022\tK12 HD000850"],"award-info":[{"award-number":["\u2022\tK12 HD000850"]}]},{"name":"National Institutes of Health","award":["75N91019D00024."],"award-info":[{"award-number":["75N91019D00024."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Early antiretroviral therapy (ART) limits viral reservoir establishment in infants but also constrains viral-specific immunity required to clear reactivated cells. In the early ART context, we evaluated whether combining adeno-associated virus serotype 9 (AAV9)\u2013vectored eCD4-IgG1 with pharmacologic latency reversal using the second mitochondria-derived activator of caspases (SMAC) mimetic AZD5582 could promote reservoir reduction and control in simian immunodeficiency virus (SIV)\u2013infected infant macaques. AAV9 delivery achieved sustained eCD4-IgG1 expression and AZD5582 induced on-ART viremia, but the combination did not reduce intact SIV proviral DNA relative to controls. Partial post-intervention control of viremia during Analytical Treatment Interruption (ATI) occurred in 2\/6 infants receiving AAV9-eCD4-IgG1 + AZD5582 with restricted reservoir expansion during recrudescence at week 13. Intact reservoir size during ATI correlated inversely with on-ART viremia during AZD5582 treatment. Controllers did not show increased eCD4-IgG1 expression nor increased on-ART viremia during AZD5582 treatment, but harbored less pre-ART intact SIV DNA in PBMCs than non-controllers. Controllers also exhibited higher frequencies and greater polyfunctionality of virus-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells prior to ATI. These findings implicate immune control of reservoir size and post-ART viral dynamics in early-treated infants and suggest that AAV9-eCD4-IgG1 + AZD5582 increases the likelihood of post-ART viral control.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.208375","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:00:50Z","timestamp":1790265650000},"source":"Crossref","is-referenced-by-count":0,"title":["T-cell responses shape infant SIV reservoirs and post-intervention control following AAV9-eCD4-Ig and latency reversal"],"prefix":"10.1172","author":[{"given":"Jairo A.","family":"Fonseca","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis C.","family":"King","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaleaha S.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"O'Hagan","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Khoei","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Alves Britto Da Costa","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camryn","family":"Cockerham","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Cottrell","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Ehnert","sequence":"additional","affiliation":[{"name":"Emory National Primate Research Center, Atlanta, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8918-8510","authenticated-orcid":true,"given":"Jennifer S.","family":"Wood","sequence":"additional","affiliation":[{"name":"Emory National Primate Research Center, Atlanta, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Alpert","sequence":"additional","affiliation":[{"name":"Emmune Inc., Cambridge, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Gardner","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Lifson","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Mavigner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio A.","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7479-9546","authenticated-orcid":true,"given":"Ann","family":"Chahroudi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,9,24]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/208375\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:00:51Z","timestamp":1790265651000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/208375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.208375"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.208375","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}