ViiV Healthcare Presents Potential Long-Acting HIV Therapies
Phase 1 data on VH184, a third-generation integrase strand transfer inhibitor, and VH499, a novel HIV-1 capsid inhibitor, highlighting their antiviral potency, safety profiles, and potential for long-acting injectable formulations.
At CROI 2025, held March 9-12 in San Francisco, we spoke with researchers from ViiV Healthcare about the latest findings from ongoing phase 1 studies of VH184, an integrase strand transfer inhibitor (INSTI), and VH499, a novel HIV-1 capsid inhibitor. The data, presented at the conference, suggest that these compounds have the potential to play a pivotal role in the future of long-acting HIV therapies.
VH184: A Long-Acting Integrase Inhibitor
VH184, a long-acting formulation of an integrase strand transfer inhibitor (INSTI), is currently being evaluated in HIV-negative adults in phase 1 trials (NCT06310551). The study's results showed promising antiviral effects, positioning VH184 as a potential long-acting injectable treatment for HIV.
Luise Rogg, MD, PhD, discovery medicine lead for VH184 at ViiV Healthcare, explained the significance of the data, “So the first thing we needed to establish as we moved into people with HIV was that it had the antiviral activity that we would expect with an INSTI. INSTIs have been the cornerstone for 15 years, and this one had to meet that mark of antiviral potency. And so that's what we were able to demonstrate in these proof-of-concept studies. That gives us a lot of support, enthusiasm, and optimism going forward as we move into the later development program."
VH499: A Potent Capsid Inhibitor with Low Drug Interaction Liability
Alongside the data for VH184, ViiV Healthcare also presented findings from a study on VH499, a new oral HIV-1 capsid inhibitor. The results showed a dose-dependent reduction in HIV-1 viral load across all doses tested (25mg, 100mg, and 250mg), with the highest dose (250mg) demonstrating a viral load reduction of -2.2 log 10 copies/mL. VH499 was well tolerated with mild to moderate adverse events, and no serious adverse events were reported.
Paul Benn, MB, ChB, FRCP, MFPM, HIV physician and early development lead for VH499 at ViiV, emphasized the importance of the compound's safety profile and efficacy, "Firstly, VH499 is really potent, it's really well tolerated, and we've previously shown that it has a low liability to cause drug interactions, which is going to be really important as we treat people aging with HIV in the future. VH499 is one of a number of partner antiretroviral agents that we're developing as long-acting drugs. This data is really encouraging as we move forward in selecting the drugs that best suit patients and patient needs."
As VH184 and VH499 move through clinical development, ViiV Healthcare's researchers acknowledge that there are still challenges to overcome before these therapies can be widely implemented. A concern is patient adherence to long-acting treatments and determining the optimal dosing intervals.
Rogg highlighted the importance of this issue, saying, “The implementation of long-acting therapies is challenging across a number of settings. Different drivers contribute to that challenge. But it's very clear. I think the thing we have to remember at ViiV is, we are the first ones who brought forth a full treatment regimen of long-acting injectables. And we are leveraging that experience, that knowledge, and we're continuing to learn as we bring Cabenuva forward to broader and broader markets.”
Benn further discussed the necessity of developing treatments that are patient-centered, noting, “We want to bring choices for patients and healthcare providers. With VH499 and VH184, and other assets we’re developing, we’re really encouraged in terms of the options we’ll be able to offer in the future. The data from the ongoing long-acting injectable phase 1 studies, combined with proof-of-concept data, will be crucial for making decisions on which drugs to move forward and which dosing regimens to pursue.”
Another area of focus is how these new therapies compare to existing long-acting options in terms of resistance prevention and improving patient outcomes. Rogg pointed to the potential advantage of VH184 in this regard, “The in vitro data we have for VH184 suggests that it has a high barrier to resistance and also the ability to maintain activity, even in the setting of some integrase-resistant mutations. This is something that will differentiate us a little bit from what’s on the market now, and it’s an important piece to bring forward as we continue in clinical development.”
Benn also highlighted the importance of VH499’s novel mechanism of action, “For VH499, it’s a new mechanism of action, so there should not be any de novo resistance out there. We know it’s highly potent, but at this point, we don’t have comparative data yet. As we move forward, we’ll generate data that shows how well it works when partnered with other agents.”
