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VH-184 – a new integrase inhibitor

The first approved integrase inhibitor was raltegravir (Isentress), followed by elvitegravir (in Stribild and later Genvoya). 

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A second generation of integrase inhibitors came with the drugs dolutegravir (in Dovato, Juluca, Tivicay and Triumeq), bictegravir (in Biktarvy) and cabotegravir (in Cabenuva).

Now, a third-generation experimental integrase inhibitor code-named VH-184 (the long-form identification number is VH-4524184) is being developed by ViiV Healthcare. This drug has long-acting potential. 

In lab experiments with cells and HIV, VH-184 is active against many strains of HIV that are partially or wholly resistant to second-generation integrase inhibitors. 

VH-184 in people

Researchers enrolled 22 people with HIV and gave them different doses of either VH-184 or placebo every three days. The doses of VH-184 used were 10, 50 and 300 mg. After 10 days, they were switched to approved regimens of ART.

The average profile of participants upon study entry was as follows:

  • age – 32 years
  • 86% assigned male at birth; 14% assigned female at birth
  • major ethno-racial groups: White (68%) and Black (14%)
  • CD4+ count – at least 500 cells/mm3
  • viral load – less than 100,000 copies/mL

All participants completed the study and had not used any HIV treatment prior to entry.

Results

The 50 mg and 300 mg doses of VH-184 every three days resulted in a 2-log decrease in viral load.

No resistance was detected by day 10.

Researchers stated that the drug was generally “well tolerated” and any side effects were generally mild. No one left the study due to side effects.

Long-acting formulations of VH-184 are being developed and plans are underway to test them for safety.

VH-184 will likely form the backbone of future long-acting HIV treatment options from ViiV.

—Sean R. Hosein

REFERENCE:

Rogg L, Nunez SA, Mingrone MV, et al. Proof-of-concept trial of VH4524184 (VH-184), a third-generation integrase strand transfer inhibitor. Program and abstracts of the 32nd Conference on Retroviruses and Opportunistic Infections, March 9-12, 2025, San Francisco. Abstract 152.