Antiviral activity against integrase resistance has been demonstrated by ViiV Healthcare’s investigational third-generation integrase inhibitor, VH4524184 (VH184). Data from this promising research, along with results from a phase I study, were presented at the 25th International AIDS Conference (AIDS 2024) in Munich, Germany. This marks the first public presentation of VH184, which is a key part of ViiV Healthcare’s long-term strategy to develop ultra long-acting HIV medicines.
GSK plc, the majority owner of ViiV Healthcare along with Pfizer and Shionogi as shareholders, announced positive in vitro findings showing that VH184 retained its antiviral activity and could be effective in countering resistance to second-generation integrase strand transfer inhibitors (INSTIs). Additional phase I study data presented included pharmacokinetic (PK) and safety results, supporting further development of VH184.
Antiviral Advancements: Dr. Kimberly Smith Highlights VH184’s Potential in Long-Acting HIV Treatment
Dr. Kimberly Smith, Head of Research & Development at ViiV Healthcare, commented: “ViiV Healthcare’s ambition is to end the HIV epidemic, in large part, by delivering a new generation of long-acting medicines for people seeking options to treat or prevent HIV. VH184, the first third-generation integrase inhibitor with the potential for long-acting dosing and coverage of INSTI resistant viruses, builds upon our legacy of developing novel agents that address unmet needs.”
The presentation at AIDS 2024 combined two separate analyses. The first analysis evaluated VH184 in vitro against more than 20 clinically derived HIV-1 viruses with mutations associated with resistance to INSTIs. These viruses were identified from two phase III clinical trials of second-generation integrase inhibitors in treatment-experienced individuals. Results indicated that VH184 has a resistance profile distinct from previous generations of INSTIs, showing retained antiviral activity against clinically relevant mutations.
The second analysis was derived from a double-blind, randomized, placebo-controlled phase I study evaluating the PK and safety of an oral version of VH184 in 84 participants without HIV. The study showed that VH184 achieved drug levels in the blood sufficient to exhibit antiviral activity against the clinically derived INSTI mutations observed in vitro. VH184 was well tolerated, with no adverse events leading to participant discontinuation. Adverse events were generally mild (n=44 in 29 participants), with few considered related to VH184 (n=6 in 5 participants, all mild) and none were serious.
Antiviral Research: ViiV Healthcare Conducts Phase I and IIa Studies on VH184 for Long-Acting HIV Treatment
Furthering their research, ViiV Healthcare is conducting a phase I study evaluating long-acting injectable formulations of VH184 in participants without HIV. Additionally, a phase IIa proof-of-concept study is underway to define the efficacy, safety, and tolerability of VH184 in people living with HIV who are naïve to antiretroviral therapy.
The first analysis presented at AIDS 2024 underscores VH184’s potential in addressing the significant challenge of INSTI resistance in HIV treatment. By retaining its antiviral activity against a broad spectrum of clinically relevant mutations, VH184 offers hope for people living with HIV who have developed resistance to existing treatments. The phase I study’s findings further bolster confidence in VH184’s development, demonstrating favorable PK properties and a strong safety profile.
This research aligns with ViiV Healthcare’s strategic vision to develop long-acting HIV treatments that can provide sustained viral suppression and reduce the frequency of dosing. The ongoing studies of VH184, including its long-acting injectable formulations, represent a significant step forward in HIV therapeutics, offering potential new options for patients seeking less frequent dosing schedules and improved adherence.
In summary, ViiV Healthcare’s presentation of early data on VH184 at AIDS 2024 highlights the promising potential of this third-generation integrase inhibitor in overcoming INSTI resistance. The combination of in vitro antiviral activity against resistant HIV strains and positive phase I safety and PK data supports the continued development of VH184. As ViiV Healthcare advances its research, VH184 could emerge as a pivotal component in the next generation of HIV treatments, contributing to the broader goal of ending the HIV epidemic.
Resource: Glaxo Smith Kline, July 23, 2024
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