{
  "abstract": "Chronic IL-1{beta}-driven inflammation contributes to cardiovascular risk and potentially HIV reservoir persistence in people with HIV (PWH); the effects of direct IL-1{beta} blockade on HIV persistence have not been defined. We show in a cohort of PWH that canakinumab, an anti-IL-1{beta} monoclonal antibody, is associated to the upregulation (Cana_Up) or the downregulation (Cana_Down) of unique sets of genes that are both associated with reduced HIV reservoir. Cana_Up genes are expressed mostly by CD4 and CD8 T cells and mapped to pathways of cell cycling (Myc, E2F, G2M) and Antigen Cross-Presentation. Th17 cells in the blood and gut tissue require IL-1 to differentiate and concomitantly express pathways reduced by canakinumab that lead to reduced reservoir. Participants with reduced reservoir after canakinumab showed significant enhancement of HIV-specific CD4 and CD8 effector function with increased frequencies of cells expressing the effector proteins IFN{gamma} and Granzyme B and the marker of degranulation CD107a. CD14+ monocytes with the highest level of IL-1{beta} also expressed the highest levels of Cana_Down genes that included inflammatory pathways (NF-kB, RELA) and PRC1/2 complex members that regulate epigenetic mediated closure of chromatin (EZH2, JARID2). These findings establish a mechanistic rationale for IL-1{beta} blockade as a therapeutic intervention that effectively target the HIV reservoir by restoring functional HIV specific adaptive immune responses and reversing monocyte driven inflammatory dysfunction.",
  "abstract_shown": true,
  "affiliations": [
    "University of California at San Francisco"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "A. A. Sharma"
    },
    {
      "name": "M. Dropathi"
    },
    {
      "name": "N. Sadek"
    },
    {
      "name": "D. Li"
    },
    {
      "name": "A. K. Dwivedi"
    },
    {
      "name": "D. Siegel"
    },
    {
      "name": "R. Rutishauser"
    },
    {
      "name": "S. Deeks"
    },
    {
      "name": "P. Hsue"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Lee"
    },
    {
      "name": "R. P. Sekaly"
    },
    {
      "name": "J. A. Tomalka"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ewyzdd1nne1m5.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.11.26362694",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.11.26362694v1.full",
  "id": "ewyzdd1nne1m5",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.11.26362694v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "hiv aids"
    ],
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7213465637",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.11.26362694v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ewyzdd1nne1m5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:47Z",
      "native_id": "10.64898/2026.09.11.26362694",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.11.26362694v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:hiv aids",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Therapeutic blockade of IL-1β in PWH reduced the HIV reservoir via mechanisms of enhanced CD8 and CD4 effector function and reversal of monocyte dysfunction",
  "title_text": "Therapeutic blockade of IL-1β in PWH reduced the HIV reservoir via mechanisms of enhanced CD8 and CD4 effector function and reversal of monocyte dysfunction",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:48Z",
  "url": "https://research.draconitic.com/paper/ewyzdd1nne1m5",
  "venue": "medRxiv",
  "versions": []
}