Can GSK’s ViiV Healthcare Deliver Twice-Yearly HIV Therapy?

Recent developments in HIV treatment highlight promising advances in long-acting antiretroviral therapy. 

ViiV Healthcare, the global specialist HIV company majority owned by GSK with Pfizer and Shionogi as shareholders, has reported encouraging early data for two investigational agents, VH184 and VH499. 

These therapies aim to reduce the frequency of dosing from daily regimens to potentially twice-yearly injections. 

The findings suggest both improved potency and tolerability, representing a significant step toward more convenient HIV management.

A third-generation integrase inhibitor

VH184, the first third-generation integrase strand transfer inhibitor (INSTI) in development, demonstrated potential for twice-yearly dosing in a phase 1 study of adults without HIV. 

Administered as a single subcutaneous or intramuscular injection, both formulations maintained drug levels for extended periods, with one sustaining steady concentrations through seven months. 

Early tolerability data show mostly mild injection site reactions, consistent with approved INSTIs, suggesting VH184 could offer a safe, long-acting alternative to daily therapies.

In vitro studies further support VH184’s potential clinical advantages. 

Compared with bictegravir, VH184 retained activity against a broad spectrum of resistant HIV strains, including viruses with multiple INSTI-associated mutations. 

This enhanced resistance profile indicates a higher barrier to resistance, a critical consideration for long-term HIV management. 

Together with its pharmacokinetic profile, these findings position VH184 as a promising candidate for ultra long-acting HIV therapy.

An investigational capsid inhibitor

VH499, an investigational capsid inhibitor, also showed potential for twice-yearly dosing in phase 1 studies. 

Single intramuscular or subcutaneous injections maintained stable drug levels for prolonged periods, supporting ultra long-acting (ULA) dosing intervals of up to six months. 

The treatment was generally well tolerated, with the most common adverse effects being mild to moderate injection site reactions and no serious adverse events or study withdrawals due to side effects.

“Our R&D efforts are built around delivering best-in-class, long-acting therapies that challenge the status quo and help make HIV treatment a smaller, less frequent part of people’s lives,” says Kimberly Smith, M.D., MPH, Head of Research & Development and Senior Vice President at ViiV Healthcare.

“The data we’re presenting on VH184, our third-generation INSTI, indicate a potential high barrier to resistance and twice-yearly dosing intervals. 

“Early results for VH499, a capsid inhibitor, point to its potential for dosing every six months. 

“These data underscore how ViiV Healthcare is working to define the future of HIV care through ultra long-acting options designed to address the needs and preferences of people living with HIV and will inform our plans to introduce the first INSTI-based, twice-yearly regimen for people with HIV.”

Implications for future HIV care

Together, VH184 and VH499 represent a shift toward longer-acting, less frequent HIV therapies. 

These early-stage results lay the groundwork for further clinical studies to optimise dosing schedules and confirm safety and efficacy in people living with HIV. 

As part of ViiV Healthcare’s broader pipeline, these agents underscore the company’s commitment to expanding treatment options that minimise the daily burden of HIV management and improve quality of life for patients.