{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:56:55Z","timestamp":1779886615688,"version":"3.53.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Functional cure has been proposed as an alternative to lifelong antiretroviral therapy and therapeutic vaccines represent one of the most promising approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We conducted a double-blind randomized placebo-controlled clinical trial to evaluate the safety, immunogenicity, and effect on viral dynamics of a therapeutic vaccine produced with monocyte-derived dendritic cells (MD-DC) loaded with a high dose of heat-inactivated autologous (HIA) HIV-1 in combination with pegylated interferon alpha 2a (IFN\u03b1-2a) in people with chronic HIV-1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty-nine male individuals on successful ART and with CD4+ \u2265450 cells\/mm<jats:sup>3<\/jats:sup> were randomized 1:1:1:1 to receive three ultrasound-guided inguinal intranodal immunizations, one every 2 weeks: (1) vaccine ~10<jats:sup>7<\/jats:sup> MD-DC pulsed with HIA-HIV-1 (10<jats:sup>10<\/jats:sup> HIV RNA copies) (<jats:italic>n<\/jats:italic> = 8); (2) vaccine plus three doses of 180 mcg IFN\u03b1-2a at weeks 4\u20136 (<jats:italic>n<\/jats:italic> = 6); (3) placebo = saline (<jats:italic>n<\/jats:italic> = 7); and (4) placebo plus three doses of 180 mcg IFN\u03b1-2a (<jats:italic>n<\/jats:italic> = 8). Thereafter, treatment was interrupted (ATI). Vaccines, IFN\u03b1-2a, and the administration procedures were safe and well tolerated. All patients\u2019 viral load rebounded during the 12-week ATI period. According to groups, changes in viral set-point between pre-ART and during ATI were not significant. When comparing all groups, there was a tendency in changes in viral set-point between the vaccine group vs. vaccine + IFN\u03b1-2a group (&amp;gt;0.5log<jats:sub>10<\/jats:sub><jats:italic>p<\/jats:italic> = 0.05). HIV-1-specific T-cell responses (IFN-\u01b4 Elispot) were higher at baseline in placebo than in the vaccine group (2,259 \u00b1 535 vs. 900 \u00b1 200 SFC\/10<jats:sup>6<\/jats:sup> PBMC, <jats:italic>p<\/jats:italic> = 0.028). A significant difference in the change of specific T-cell responses was only observed at week 4 between vaccine and placebo groups (694 \u00b1 327 vs. 1,718 \u00b1 282 SFC\/10<jats:sup>6<\/jats:sup> PBMC, <jats:italic>p<\/jats:italic> = 0.04). No effect on T-cell responses or changes in viral reservoir were observed after INF\u03b1-2a administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Results from this study show that intranodally administered DC therapeutic vaccine in combination with IFN\u03b1-2a was safe and well-tolerated but had a minimal impact on viral dynamics in HIV-1 chronic infected participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p>(<jats:uri>www.ClinicalTrials.gov<\/jats:uri>), identifier NCT02767193<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.767370","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T15:08:00Z","timestamp":1638976080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon \u03b1-2a on Viral Control Following ART Discontinuation: A Phase 2A Randomized Clinical 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