{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:08:00Z","timestamp":1785424080736,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFC2306804"],"award-info":[{"award-number":["2023YFC2306804"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2025ZD01905305"],"award-info":[{"award-number":["2025ZD01905305"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271857"],"award-info":[{"award-number":["82271857"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82271857"],"award-info":[{"award-number":["82271857"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>HIV reservoir size and decay represent distinct dimensions of viral persistence, yet whether they are governed by shared or separable immunological mechanisms during early antiretroviral therapy (ART) remains unclear. In this study, we employed multiparameter flow cytometry and bulk RNA sequencing to analyze longitudinal immune profiles across 21 treatment-na\u00efve people living with HIV before ART initiation and at 1 and 5 months thereafter. Our findings revealed an apparent dissociation between HIV-1 DNA levels and decay rates in peripheral blood, and the two indicators appear to be relatively independent dimensions of viral persistence. Specifically, lower HIV-1 DNA levels were associated with higher frequencies of cytotoxic and adaptive-like natural killer (NK) cell subsets, whereas faster HIV-1 DNA decay was linked to restored HIV-specific CD4+ and CD8+ T-cell responses during treatment. Notably, transcriptomic analyses uncovered divergent gene expression signatures related to B cell-associated immunity and type I interferon pathways, with individuals with higher HIV-1 DNA levels exhibiting elevated expression of immunoglobulin and interferon-stimulated genes, while faster decay correlated with enrichment of antiviral and complement-related genes. Collectively, these findings provide a preliminary characterization of immune correlates of peripheral blood total HIV-1 DNA dynamics in the early phase following ART initiation. This work offers potential immune clues for exploring the viral reservoir and generates testable hypotheses for validation in future large cohorts.<\/jats:p>","DOI":"10.3390\/cells15131161","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:49:23Z","timestamp":1782434963000},"page":"1161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Innate and Adaptive Immune Modules Differentially Associate with HIV Reservoir Size and Decay During Early Antiretroviral Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-0415","authenticated-orcid":false,"given":"Wei-Zhe","family":"Li","sequence":"first","affiliation":[{"name":"Medical School of Chinese People\u2019s Liberation Army (PLA), Beijing 100853, China"},{"name":"Senior Department of Infectious Diseases, Chinese PLA General Hospital, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Huang","family":"Huang","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, Chinese PLA General Hospital, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology & Microbiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, Chinese PLA General Hospital, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Ju","family":"Zhou","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, Chinese PLA General Hospital, Beijing 100039, 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Hospital, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, Chinese PLA General Hospital, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0809-9207","authenticated-orcid":false,"given":"Xing","family":"Fan","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, Chinese PLA General Hospital, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Mei","family":"Jiao","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, Chinese PLA General Hospital, Beijing 100039, 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