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Updated: Jul 8, 2026
05:46
Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
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Phase 1 Evaluation of VH4524184, a Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance
Luise Rogg1, Mark Underwood1, Nathan Hanan2
1ViiV Healthcare, Durham, North Carolina, USA.
Summary
VH-184, a novel integrase strand transfer inhibitor (INSTI), shows a favorable safety profile and long-acting potential for HIV-1 treatment. It retains activity against resistant strains, supporting its further development.
Area of Science:
- Antiviral drug development
- HIV-1 therapeutics
- Pharmacology
Background:
- Integrase strand transfer inhibitors (INSTIs) are crucial for HIV-1 treatment.
- VH4524184 (VH-184) is a promising third-generation INSTI with long-acting potential.
Purpose of the Study:
- To evaluate the safety, tolerability, and pharmacokinetics of oral VH-184 in a first-time-in-human study.
- To assess VH-184's in vitro resistance profile against INSTI-resistant HIV-1 strains.
Main Methods:
- Phase 1, double-blind, randomized, placebo-controlled study of single and multiple ascending doses of VH-184.
- Pharmacokinetic assessments, including drug-drug interaction with midazolam and food effect.
- In vitro evaluation of VH-184 against pseudotyped viruses with resistance mutations.
Main Results:
- VH-184 demonstrated a good safety and tolerability profile across dose ranges.
- Dose-proportional pharmacokinetics were observed up to 300 mg, with a half-life of approximately 24 hours.
- VH-184 maintained antiviral activity against second-generation INSTI-resistant HIV-1 strains.
Conclusions:
- The study supports the safety and further development of VH-184.
- VH-184 shows potential as a long-acting, third-generation INSTI for HIV-1 treatment.
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