{
  "abstract": "Background: VH4524184 (VH-184) is an emerging third-generation integrase strand transfer inhibitor (INSTI) with an enhanced in vitro resistance profile compared with second-generation INSTIs being developed as a long-acting antiretroviral therapy (ART) for human immunodeficiency virus type 1 (HIV-1). We present data from a proof-of-concept phase 2a trial of VH-184 in people with HIV-1.\n\nMethods: This randomized, double-blind, placebo-controlled trial evaluated oral VH-184 monotherapy in adults naive to ART with HIV-1 RNA ≥ 3000 copies/mL. Participants received oral VH-184 10, 50, or 300 mg or placebo on days 1 (baseline), 4, and 7. On day 10, participants initiated standard-of-care ART. The primary endpoint was maximum change from baseline in plasma HIV-1 RNA through day 10. Secondary endpoints included safety, tolerability, exposure–response relationship, CD4+ cell effects, and treatment-emergent resistance.\n\nResults: Of 22 participants enrolled (VH-184, n = 19; placebo, n = 3), 86% were male, 68% were White, and median age was 32 years. Mean maximum change from baseline through day 10 in HIV-1 RNA was −1.17, −2.15, and −2.31 log10 copies/mL for VH-184 10, 50, and 300 mg, respectively. No adverse events (AEs) leading to withdrawal, treatment-emergent serious AEs, or deaths occurred. There were no clinically relevant changes in safety laboratory parameters, electrocardiograms, or vital signs. No VH-184 genotypic or phenotypic resistance was detected through day 10.\n\nConclusions: Monotherapy with VH-184 demonstrated rapid and potent antiviral activity and a favorable safety and tolerability profile. The established exposure–response model and efficacy and safety results support further development of VH-184 as the core agent in complete ART regimens for HIV-1 (ClinicalTrials.gov, NCT06214052).",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "Luise Rogg"
    },
    {
      "name": "Sebastian A Nuñez",
      "orcid": "0000-0002-8865-138X"
    },
    {
      "name": "María Verónica Mingrone"
    },
    {
      "name": "Pere Domingo",
      "orcid": "0000-0003-1138-5770"
    },
    {
      "name": "Charlotte-Paige Rolle",
      "orcid": "0000-0002-6444-2225"
    },
    {
      "name": "Roberto Güerri-Fernandez",
      "orcid": "0000-0002-9794-9161"
    },
    {
      "name": "Vicente Estrada",
      "orcid": "0000-0002-7795-5986"
    },
    {
      "name": "Monica Lopez"
    },
    {
      "name": "Nathan Hanan"
    },
    {
      "name": "Gabriela L Ghita",
      "orcid": "0000-0001-5956-2372"
    },
    {
      "name": "Jerry L Jeffrey"
    },
    {
      "name": "Mark Underwood"
    },
    {
      "name": "Jose R Castillo-Mancilla",
      "orcid": "0000-0003-1242-1745"
    },
    {
      "name": "Fiona Halliday"
    },
    {
      "name": "Ebele Ezeadi"
    },
    {
      "name": "Martin Gartland"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3wjg378xkg7xz.bib",
  "cited_by": 1,
  "doi": "10.1093/cid/ciag357",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715974/",
  "id": "3wjg378xkg7xz",
  "issns": [
    "1058-4838",
    "1537-6591"
  ],
  "landing_url": "https://doi.org/10.1093/cid/ciag357",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/MED00290"
    ],
    [
      "heading",
      "HIV/AIDs"
    ],
    [
      "heading",
      "Major Article"
    ],
    [
      "openalex",
      "2725|HIV/AIDS drug development and treatment"
    ]
  ],
  "openalex": "W7164496023",
  "pdf_url": null,
  "pmcid": "PMC13715974",
  "pmid": "42283218",
  "published": "2026-06-12",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/3wjg378xkg7xz.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:23:08Z",
      "native_id": "PMC13715974",
      "source": "pmc",
      "url": "https://doi.org/10.1093/cid/ciag357"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|HIV/AIDS drug development and treatment",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Proof-of-Concept Phase 2a Trial of VH4524184: An Emerging Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile",
  "title_text": "Proof-of-Concept Phase 2a Trial of VH4524184: An Emerging Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:23:08Z",
  "url": "https://research.draconitic.com/paper/3wjg378xkg7xz",
  "venue": "Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America",
  "versions": []
}