Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2025
Phase 1 Evaluation of VH4524184, a Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05631704 (A Phase 1 Double-Blind), which is not on this map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Double-Blind (Sponsor-unblinded), Placebo-Controlled Randomized, Single and Multiple Ascending Dose First-Time-in-Human Study to Investigate the Safety, Tolerability, and Pharmacokinetics of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity
Who cites it
2 citing papers in PubMed.
- Prevalence of acquired resistance to HIV integrase strand transfer inhibitors (INSTIs) in clinical samples from treatment-experienced patients in Chile, 2012-2023.Journal of virus eradication · 2025Article
- Persistent cell-associated HIV-1 RNA in virally suppressed individuals on INSTI-based ART.Journal of virus eradication · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
backgroundIntegrase strand transfer inhibitors (INSTIs) have been fundamental to human immunodeficiency virus type 1 (HIV-1) treatment for over 15 years. VH4524184 (VH-184) is a third-generation INSTI with long-acting potential currently in development for HIV-1 treatment.
methodsThis double-blind, randomized, placebo-controlled, phase 1, first-time-in-human (FTIH) study evaluated oral VH-184 in adults without HIV-1 administered as single ascending doses (10-460 mg; part 1), multiple ascending doses (160-480 mg) for 14 days with concomitant midazolam (480 mg cohort; part 2), and as a single dose (100 mg) under fasted/fed conditions (part 3) to assess safety, tolerability, and pharmacokinetics. VH-184 resistance was evaluated in vitro against pseudotyped viruses containing participant-derived integrase sequences from the SAILING and DAWNING studies that conferred reduced susceptibility to second-generation INSTIs.
resultsEighty-four participants (VH-184, n = 63; placebo, n = 21) were included in the FTIH study. VH-184 demonstrated a good safety and tolerability profile. Dose-proportional increases in exposures were observed after single doses of 10-300 mg, without further increase after 460 mg single or 480 mg multiple doses. Geometric mean half-life was approximately 24 hours. Observed accumulation in exposures ranged from 1.3- to 1.9-fold after repeat VH-184 dosing of 480 and 160 mg, respectively. VH-184 had minimal impact on the pharmacokinetics of CYP3A substrates and exhibited a moderate positive food effect. The in vitro resistance profile of VH-184 was enhanced compared with prior INSTIs, retaining antiviral activity against second-generation INSTI-resistant pseudotyped viruses.
conclusionsThese data support the safety and further development of VH-184 as a third-generation INSTI with long-acting potential for HIV-1 treatment. Clinical Trials Registration. NCT05631704.
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