{
  "abstract": "Background: Elite controllers (ECs) are people with HIV (PWH) who suppress viral replication without antiretroviral therapy (ART). A subset, often termed exceptional elite controllers (EECs), harbor very small viral reservoirs, with few intact proviruses integrated into inactive chromosomal regions. Defining inflammatory signatures in ECs may clarify whether some approach a functionally cured state. Methods: We measured 384 plasma proteins in ART-naive ECs (n=62), ART-suppressed non-controllers (n=37), and people without HIV (PwoH) (n=50) using Olink proteomics, and compared proteomic profiles, clinical parameters, and intact reservoir data using FLIP-Seq. Hierarchical clustering identified ECs whose proteomic profiles most closely resembled PWoH; this subset was further analyzed using machine-learning approaches. Results: ART-suppressed non-controllers had higher inflammatory protein levels than ART-naive ECs, yet ECs still showed elevated inflammation and lower CD4:CD8 ratios compared with PWoH. Clustering analysis revealed a distinct subset of ECs (n=9) whose profiles closely matched those without HIV (ECs with PWoH-like proteomic profiles), a pattern not observed in ART-suppressed non-controllers. Compared to typical ECs, ECs with PWoH-like proteomic profiles had consistently lower IL-1{beta}, SCRN1, and BID, numerically lower intact proviral frequencies, and a high frequency of protective HLA alleles. Machine-learning analyses highlighted features that most strongly differentiated ECs with PWoH-like proteomic profiles from typical ECs, including reduced gut mucosal/intestinal epithelial-associated proteins, higher absolute CD4 counts, and lower levels of pro-inflammatory cytokines and cellular immune activation. Conclusions: These findings identify a subset of ECs with a PWoH-like inflammatory proteomic profile, accompanied by numerically lower intact HIV reservoirs and a high frequency of protective HLA alleles. Defining the mechanisms associated with this low-inflammatory state may provide insights into exceptional HIV control and inform strategies for durable HIV remission.",
  "abstract_shown": true,
  "affiliations": [
    "Division of HIV, Infectious Diseases, and Global Medicine, UCSF, San Francisco, CA, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "name": "S. D. Falcinelli"
    },
    {
      "name": "D. P. Maison"
    },
    {
      "name": "I. Avila-Vargas"
    },
    {
      "name": "T. Dalhuisen"
    },
    {
      "name": "C. Jiang"
    },
    {
      "name": "X. Lian"
    },
    {
      "name": "C. Gao"
    },
    {
      "name": "M.-G. Shin"
    },
    {
      "name": "R. Thomas"
    },
    {
      "name": "J. Feng"
    },
    {
      "name": "J. Salazar"
    },
    {
      "name": "R. Hoh"
    },
    {
      "name": "J. N. Martin"
    },
    {
      "name": "S. P. Deeks"
    },
    {
      "name": "P. W. Hunt"
    },
    {
      "name": "M. Lichterfeld"
    },
    {
      "name": "X. Yu"
    },
    {
      "name": "T. J. Henrich"
    },
    {
      "affs": [
        0
      ],
      "name": "M. J. Peluso"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a5dr2evtbxven.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.06.749753",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749753v1.full",
  "id": "a5dr2evtbxven",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749753v1",
  "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": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7212848126",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749753v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a5dr2evtbxven.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:59Z",
      "native_id": "10.64898/2026.09.06.749753",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749753v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Plasma Proteomic Profiling Identifies a Subset of HIV Elite Controllers with Inflammatory Profiles Resembling People Without HIV",
  "title_text": "Plasma Proteomic Profiling Identifies a Subset of HIV Elite Controllers with Inflammatory Profiles Resembling People Without HIV",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:59Z",
  "url": "https://research.draconitic.com/paper/a5dr2evtbxven",
  "venue": "bioRxiv",
  "versions": []
}