{
  "abstract": "A key goal in HIV-1 cure research is to understand why some individuals control viral rebound after stopping antiretroviral therapy (ART). Recent human studies have identified responding CD8+ T cells expressing Ki-67 and the transcription factor TCF-1 as correlates of post-treatment control, but the mechanistic basis of this association remains unclear. Using the theoretical framework of Conway and Perelson, we fit mechanistic within-host models to viral load and CD8+ T cell data from 9 individuals in a combination immunotherapy trial following ART interruption. Although Ki-67 and TCF-1 measurements were not used for fitting, the inferred effector cell expansion sensitivity, i.e., the responsiveness of effector expansion to low antigen levels, shows a strong linear relationship with Ki-67 and TCF-1 levels at rebound (Pearsons r {approx} 0.8). Building on this, we show analytically that the post-rebound viral load set point is inversely proportional to the effector cell expansion sensitivity, and thus strongly correlates with cycling (Ki-67+) CD8+ T cells (r {approx} -0.8) at rebound, and a subset that expresses TCF-1 (r {approx} -0.9). In effect, individuals with a larger proportion of CD8+ T cells responding to viral rebound, and a greater representation of TCF-1 expressing cells within the responding subset, achieve markedly lower viral set points through a higher effector cell expansion sensitivity. This mechanism is consistent with prior modeling in a non-intervention ATI setting, suggesting it may generalize across more rebound contexts. Our results provide a mechanistic explanation why both Ki-67+ responding CD8+ T cells and their TCF-1-expressing subset predict post-treatment control, linking clinical correlation to its underlying cause and highlighting Ki-67 and TCF-1 as potential early biomarkers of HIV immunotherapy success.",
  "abstract_shown": true,
  "affiliations": [
    "Los Alamos National Laboratory"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "T. Phan"
    },
    {
      "name": "N. Pagane"
    },
    {
      "name": "J. A. F. Kreig"
    },
    {
      "name": "A. Marc"
    },
    {
      "name": "M. Locke"
    },
    {
      "name": "M. J. Peluso"
    },
    {
      "name": "D. A. Sandel"
    },
    {
      "name": "A. N. Deitchman"
    },
    {
      "name": "R. L. Rutishauser"
    },
    {
      "name": "S. G. Deeks"
    },
    {
      "name": "R. Ke"
    },
    {
      "name": "R. M. Ribeiro"
    },
    {
      "name": "A. S. Perelson"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eme9190b10t5z.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.28.747758",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747758v1.full",
  "id": "eme9190b10t5z",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747758v1",
  "language": null,
  "licence": "CC0-1.0",
  "licence_label": "CC0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/publicdomain/zero/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7204943254",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747758v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/eme9190b10t5z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:06Z",
      "native_id": "10.64898/2026.08.28.747758",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747758v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "A mechanistic basis for CD8+ T cell expansion sensitivity as a predictor of HIV post-treatment control",
  "title_text": "A mechanistic basis for CD8+ T cell expansion sensitivity as a predictor of HIV post-treatment control",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:06Z",
  "url": "https://research.draconitic.com/paper/eme9190b10t5z",
  "venue": "bioRxiv",
  "versions": []
}