{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T18:53:48Z","timestamp":1781463228796,"version":"3.54.1"},"reference-count":47,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005561","name":"North Carolina Department of Health and Human Services","doi-asserted-by":"crossref","award":["UM1TR004406"],"award-info":[{"award-number":["UM1TR004406"]}],"id":[{"id":"10.13039\/100005561","id-type":"DOI","asserted-by":"crossref"}]},{"name":"EU","award":["SRIA2015-1066"],"award-info":[{"award-number":["SRIA2015-1066"]}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["HSN272201100021I"],"award-info":[{"award-number":["HSN272201100021I"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH Division of AIDS","award":["HHSN27200037"],"award-info":[{"award-number":["HHSN27200037"]}]},{"DOI":"10.13039\/100000866","name":"IAVI","doi-asserted-by":"crossref","award":["IAVI"],"award-info":[{"award-number":["IAVI"]}],"id":[{"id":"10.13039\/100000866","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Euopean Commission Horizon 2020","award":["681137"],"award-info":[{"award-number":["681137"]}]},{"name":"NIH Division of AIDS","award":["U01AI131310"],"award-info":[{"award-number":["U01AI131310"]}]},{"name":"NIH Division of AIDS","award":["P30AI050410"],"award-info":[{"award-number":["P30AI050410"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Approaches to achieving antiretroviral therapy\u2013free (ART-free) remission from HIV-1 must consider that people over 50 years now comprise the majority of people with HIV (PWH) on ART in various regions, including the United States.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We report a double-blind, randomized trial in which PWH on ART, aged 21\u201360 years, received modified vaccinia Ankara\u2013vectored (MVA-vectored) vaccines, MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4), either alone or in combination (\n                      <jats:italic>n<\/jats:italic>\n                      = 7\/group), or saline placebo (\n                      <jats:italic>n<\/jats:italic>\n                      = 3). M3 and M4 contain complementary HIVconsvX immunogens that each span the same regions in HIV-1 Gag and Pol but differ by approximately 8% at the amino acid level.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      M3, M4, and M3M4 regimens were well tolerated and all significantly increased both the frequency (peak median increase ~3-fold) and breadth of the HIVconsvX-specific T cell response while redirecting T cells to target conserved regions in HIV-1 for up to 10 weeks after vaccination. We also demonstrated that vaccination increased frequencies of T cells targeting participant autologous HIV-1 sequences. Vaccination mostly expanded preexisting HIV-1\u2013specific T cells and did not impact CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell activation, low-level viremia, or integrated HIV-1 provirus. Linear regression indicated that age was independently and negatively associated with the change in T cell frequency at 1, 2, and 10 weeks after vaccination (~1.41-fold decrease per 10 years older). After adjusting for age, years on ART was positively associated with HIVconsvX-specific T cell frequencies at 1 and 2 weeks following vaccination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>In PWH receiving ART, MVA.HIVconsvX vaccines significantly increased T cells targeting conserved regions of HIV-1. Novel strategies may be required to enhance anti\u2013HIV-1 immunity in older adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT03844386<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>NIH National Institute of Allergy and Infectious Diseases (NIAID) grants U01AI131310, HHSN272201100021I\/HHSN27200037 (subcontract OX-14007.004.0037-212), UM1TR004406, P30AI050410, and P30CA016086; International AIDS Vaccine Initiative; European and Developing Countries Clinical Trials Partnership SRIA2015-1066; European Commission\u2019s Horizon 2020 Research and Innovation Programme 681137.<\/jats:p>\n                  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