ViiV Healthcare highlights promising investigational treatments designed to deliver long-acting HIV control with just two doses per year, aiming to improve adherence and patient convenience.
ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, has unveiled promising early-stage data from its next-generation long-acting HIV treatment pipeline. The findings, presented at the Conference on Retroviruses and Opportunistic Infections 2026 in Denver, Colorado, highlight the potential for twice-yearly dosing regimens that could significantly reduce the treatment burden for people living with HIV.
Advancing a Third-Generation INSTI: VH184
Central to the company’s presentation was new data on VH184, a novel, third-generation integrase strand transfer inhibitor (INSTI) currently in development as a long-acting injectable therapy. INSTIs are a cornerstone of modern HIV treatment, working by blocking the integrase enzyme that HIV uses to insert its genetic material into human cells. While second-generation INSTIs such as bictegravir have transformed care, resistance mutations remain a concern in certain patient populations.
VH184 is designed to address these limitations while also offering extended dosing intervals. In a Phase 1 study involving adults without HIV, long-acting formulations of VH184 were administered as a single subcutaneous (SC) or intramuscular (IM) injection. Two different formulations were evaluated to assess pharmacokinetics, safety, and tolerability.
The results were encouraging. Both formulations demonstrated long-acting properties, with one formulation maintaining steady plasma drug concentrations through Month 7 following a single injection. These sustained levels suggest the potential for dosing intervals of up to six months, positioning VH184 as a candidate for twice-yearly administration.
From a safety perspective, VH184 was generally well tolerated. The majority of adverse events were mild, grade 1 injection site reactions (ISRs), including erythema, pain, and nodules. A smaller number of grade 2 and grade 3 ISRs were reported, but there were no unexpected safety signals. Importantly, the overall safety profile was consistent with previously approved INSTIs, reinforcing confidence in the drug’s development pathway.
Enhanced Resistance Profile Compared to Bictegravir
Beyond pharmacokinetics, ViiV Healthcare also presented in-vitro data examining the antiviral potency and resistance profile of VH184. When tested against HIV strains harboring mutations associated with resistance to second-generation INSTIs, VH184 demonstrated improved activity compared to bictegravir.
The compound retained antiviral efficacy across a broad range of resistant viral strains, including those carrying multiple INSTI-associated substitutions. These findings indicate that VH184 may have a higher barrier to resistance, a critical feature for long-acting therapies where missed doses or prolonged drug exposure at suboptimal levels could otherwise increase the risk of resistance development.
Together, the Phase 1 and laboratory data confirm VH184 as a true third-generation INSTI candidate with both long-acting potential and extended coverage against resistant HIV variants. The program is now advancing toward Phase 2b trials, which will further refine dosing strategies and evaluate its clinical performance in people living with HIV. If successful, VH184 could become the backbone of the first INSTI-based, twice-yearly treatment regimen.
VH499: A Long-Acting Capsid Inhibitor
In addition to VH184, ViiV Healthcare presented new data on VH499, an investigational capsid inhibitor that represents another promising component of the company’s ultra long-acting (ULA) pipeline. Capsid inhibitors target the protective protein shell of the virus, interfering with multiple stages of the viral lifecycle, including assembly and replication.
In an ongoing Phase 1 study involving adults without HIV, VH499 was administered as a single IM or SC injection at doses ranging from 100 mg to 1200 mg. Both routes of administration demonstrated stable and sustained drug levels over an extended period, supporting the potential for dosing intervals of up to six months.
Safety findings were similarly reassuring. VH499 was generally well tolerated, with the most common adverse events being injection site reactions, particularly mild to moderate pain at the injection site. These reactions were typically short-lived. Notably, there were no serious adverse events reported and no study withdrawals due to adverse events, underscoring the favorable early safety profile of the compound.
The new data build upon proof-of-concept findings presented at the previous year’s CROI meeting and strengthen the case for VH499 as a viable candidate for ultra long-acting regimens. Future studies will focus on optimizing dose selection and evaluating combination strategies with other long-acting agents.
A Vision for Ultra Long-Acting HIV Care
The advances in VH184 and VH499 are part of a broader strategic effort by ViiV Healthcare to redefine HIV treatment through innovation in long-acting therapies. The company has already played a pioneering role in the development of long-acting regimens, and its pipeline now reflects a next wave of ultra long-acting solutions designed to reduce treatment frequency even further.
In addition to VH184 and VH499, the company continues to progress other ULA assets, including lotivibart (N6LS), a broadly neutralizing antibody candidate under investigation for HIV treatment and prevention. These assets collectively reflect a comprehensive approach to long-acting HIV care that integrates novel mechanisms of action with optimized pharmacokinetic profiles.
Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, emphasized that the company’s R&D strategy is centered on delivering best-in-class therapies that challenge conventional treatment paradigms. By reducing dosing frequency from daily pills to potentially twice-yearly injections, ViiV aims to make HIV management a smaller and less intrusive part of patients’ lives.
This shift has significant implications. Long-acting regimens can help improve adherence, reduce stigma associated with daily medication use, and provide greater flexibility for individuals managing chronic HIV infection. For patients with resistance mutations or those who struggle with daily oral therapy, these innovations may expand therapeutic options and improve long-term outcomes.
