{
  "abstract": "Background\n\nLenacapavir (LEN) is a first-in-class, long-acting HIV-1 capsid inhibitor, approved for the treatment of heavily treatment-experienced (HTE) people with HIV (PWH) with multidrug resistance (MDR). To date, few data are available on resistance profiles in real life.Methods\n\nPaired plasma and PBMC samples from nine HTE PWH with MDR enrolled in the PRESTIGIO Registry receiving LEN in combination with an optimized background regimen were collected before (baseline) and during LEN treatment. Next-generation sequencing was performed using in-house protocols. LEN susceptibility was assessed by single-cycle assay. Intra-patient viral evolution was evaluated through quasispecies distance analysis.Results\n\nAt baseline, no major LEN resistance-associated mutations were detected; the accessory capsid polymorphism T107A was identified as a minority variant (5.9%) in one case, with phenotypic assays confirming full LEN susceptibility (mean fold-change: 1.2). Participants received LEN for a median [IQR] of 19.8 [18.5-23.2] months. Two individuals started LEN with undetectable viremia and maintained suppression. The other seven participants were viremic; six achieved viral suppression, with one experiencing a blip. One low-adherent participant exhibited persistent viremia with Q67K and K70H as the majority variants in both plasma (98.5%; 97.8%) and PBMCs (75.7%; 75.6%), conferring a 2081-fold reduction in LEN susceptibility. Intra-host variability in the capsid and pol regions remained low over time and across compartments.Conclusions\n\nIn this case series of HTE PWH with MDR, LEN was highly associated with maintenance or achievement of virological suppression and limited virus evolution, with only one participant remaining viremic and showing a majority highly LEN-resistant variant.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Experimental Medicine, University of Rome 'Tor Vergata', Via Montpellier 1, Rome 00133, Italy.",
    "Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.",
    "Department of Medical Biotechnologies, University of Siena, Siena, Italy.",
    "Infectious Disease Clinic, University of Modena and Reggio Emilia, AOU Policlinico di Modena, Modena, Italy.",
    "Infectious Diseases Unit, San Martino Hospital Genoa, University of Genoa, Genoa, Italy.",
    "Infectious Diseases Unit, Azienda Scaligera di Verona, Verona, Italy.",
    "Department of Clinical and Experimental Sciences, University of Brescia-ASST Spedali Civili, Brescia, Italy.",
    "Clinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.",
    "S.C. Malattie Infettive, ASST Ovest Milanese, Legnano General Hospital, Legnano, Italy.",
    "Department of Biomedical and Clinical Sciences, Università Degli Studi di Milano, Milan, Italy.",
    "Infectious Diseases Unit, Vita-Salute San Raffaele University, Milan, Italy."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maria Mercedes Santoro"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniele Spalletta",
      "orcid": "0009-0009-4932-5344"
    },
    {
      "affs": [
        1
      ],
      "name": "Vincenzo Spagnuolo",
      "orcid": "0000-0002-9656-7217"
    },
    {
      "affs": [
        2
      ],
      "name": "Chiara Paletti"
    },
    {
      "affs": [
        0
      ],
      "name": "Greta Marchegiani"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Concetta Bellocchi"
    },
    {
      "affs": [
        1
      ],
      "name": "Riccardo Lolatto"
    },
    {
      "affs": [
        0
      ],
      "name": "Luca Carioti",
      "orcid": "0000-0003-1713-8682"
    },
    {
      "affs": [
        3
      ],
      "name": "Adriana Cervo",
      "orcid": "0000-0002-1384-7847"
    },
    {
      "affs": [
        4
      ],
      "name": "Antonio Di Biagio"
    },
    {
      "affs": [
        5
      ],
      "name": "Marta Fiscon"
    },
    {
      "affs": [
        6
      ],
      "name": "Emanuele Focà",
      "orcid": "0000-0003-4395-5379"
    },
    {
      "affs": [
        7
      ],
      "name": "Roberta Gagliardini"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Stefano Rusconi",
      "orcid": "0000-0002-0375-9990"
    },
    {
      "affs": [
        2
      ],
      "name": "Maurizio Zazzi",
      "orcid": "0000-0002-0344-6281"
    },
    {
      "affs": [
        1,
        10
      ],
      "name": "Antonella Castagna",
      "orcid": "0000-0002-8338-9714"
    },
    {
      "affs": [
        2
      ],
      "name": "Francesco Saladini",
      "orcid": "0000-0002-9934-377X"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesca Ceccherini-Silberstein"
    },
    {
      "name": "PRESTIGIO Registry"
    },
    {
      "name": "the"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4zabf337tyzj6.bib",
  "cited_by": 0,
  "doi": "10.1093/jac/dkag335",
  "fulltext_url": "https://europepmc.org/articles/PMC13714547",
  "id": "4zabf337tyzj6",
  "issns": [
    "0305-7453",
    "1460-2091"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948967",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
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      "AcademicSubjects/MED00230"
    ],
    [
      "heading",
      "AcademicSubjects/MED00290"
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    [
      "heading",
      "AcademicSubjects/MED00740"
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    [
      "heading",
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    [
      "openalex",
      "2725|HIV/AIDS drug development and treatment"
    ]
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  "openalex": "W7224099316",
  "pdf_url": "https://europepmc.org/articles/PMC13714547?pdf=render",
  "pmcid": "PMC13714547",
  "pmid": "42948967",
  "published": "2026-10-01",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/4zabf337tyzj6.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:35Z",
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      "source": "europepmc",
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    },
    {
      "first_seen": "2026-11-01T12:22:01Z",
      "native_id": "PMC13714547",
      "source": "pmc",
      "url": "https://doi.org/10.1093/jac/dkag335"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|HIV/AIDS drug development and treatment",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Virological outcomes, resistance profile and viral evolution of lenacapavir-based regimens in heavily treatment-experienced people: data from the PRESTIGIO Registry.",
  "title_text": "Virological outcomes, resistance profile and viral evolution of lenacapavir-based regimens in heavily treatment-experienced people: data from the PRESTIGIO Registry.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:01Z",
  "url": "https://research.draconitic.com/paper/4zabf337tyzj6",
  "venue": "The Journal of antimicrobial chemotherapy",
  "versions": []
}