Proof-of-Concept Phase 2a Trial of VH4524184: An Emerging Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile
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.
Methods: 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.
Results: 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.
Conclusions: 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).
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BibTeX
@article{rogg2026proofofconcept,
title = {{Proof-of-Concept Phase 2a Trial of VH4524184: An Emerging Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile}},
author = {Luise Rogg and Sebastian A Nuñez and María Verónica Mingrone and Pere Domingo and Charlotte-Paige Rolle and Roberto Güerri-Fernandez and Vicente Estrada and Monica Lopez and Nathan Hanan and Gabriela L Ghita and Jerry L Jeffrey and Mark Underwood and Jose R Castillo-Mancilla and Fiona Halliday and Ebele Ezeadi and Martin Gartland},
journal = {Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America},
year = {2026},
month = jun,
doi = {10.1093/cid/ciag357},
url = {https://doi.org/10.1093/cid/ciag357},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Proof-of-Concept Phase 2a Trial of VH4524184: An Emerging Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile
AU - Luise Rogg
AU - Sebastian A Nuñez
AU - María Verónica Mingrone
AU - Pere Domingo
AU - Charlotte-Paige Rolle
AU - Roberto Güerri-Fernandez
AU - Vicente Estrada
AU - Monica Lopez
AU - Nathan Hanan
AU - Gabriela L Ghita
AU - Jerry L Jeffrey
AU - Mark Underwood
AU - Jose R Castillo-Mancilla
AU - Fiona Halliday
AU - Ebele Ezeadi
AU - Martin Gartland
PY - 2026
DA - 2026/06/12
JO - Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
DO - 10.1093/cid/ciag357
UR - https://doi.org/10.1093/cid/ciag357
AB - 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. Methods: 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. Results: 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. Conclusions: 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).
SN - 1058-4838
SN - 1537-6591
ER -