VH-499 – a new capsid inhibitor
VH-499 (the long-form identification number is 4011499) interferes with an HIV protein called the capsid. This drug has potential to be used as part of a long-acting anti-HIV treatment.
VH-499 does not interfere with a group of enzymes used to break down many medicines.
In a clinical trial, different doses of VH-499 (25 mg to 250 mg every five days) or placebo were given to 23 people who had not previously used HIV treatment (ART). Doses were given on days 1 and 6. On day 11, participants were given approved ART.
The average profile of participants upon study entry was as follows:
- age – 31 years
- 83% assigned male at birth; 17% assigned female at birth
- body mass index (BMI) – 24 kg/m2
- CD4+ count – 481 cells/mm3
- viral load – 71,000 copies/mL
Participants were recruited from Canada, Argentina, France, Germany, Italy, Mexico, Spain, the UK and the U.S.
Results
The greatest decrease in viral load was seen with the 250-mg dose of VH-499. This resulted in a decline of more than 2 logs (vs. 0.18 log with placebo).
Nineteen out of 20 people given VH-499 did not have any resistance detected. One person who received the lowest dose of VH-499 (25 mg) developed HIV that could resist the drug by the sixth day of the study. This person was subsequently given dolutegravir + 3TC on day 11 and within several weeks had a viral load of 69 copies/mL. Subsequently, their viral load fell to less than 20 copies/mL.
Side effects were generally mild—mostly headache. No major changes to lab test results occurred.
For the future
ViiV is developing long-acting formulations of VH-499 and further clinical trials are planned.
—Sean R. Hosein
REFERENCE:
Griesel R, Nunez SA, Perez Rios AM, et al. Proof-of-concept trial of oral VH4011499 (VH-499), a new HIV-1 capsid inhibitor. Program and abstracts of the 32nd Conference on Retroviruses and Opportunistic Infections, March 9-12, 2025, San Francisco. Abstract 153.