2026-03-05 バッファロー大学（UB）
＜関連情報＞
- https://www.buffalo.edu/news/releases/2026/03/HIV-antibodies-research.html
- https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.70488
ウイルス血症中のHIV-1広域中和抗体VRC07-523-LSのクリアランス促進：試験設計と解析への影響 Enhanced Clearance of HIV-1 Broadly Neutralizing Antibody VRC07-523-LS During Viremia: Influences on Trial Design and Analysis
Nicholas M. Smith, Brian M. Ho, Katharine J. Bar, Lucio Gama, Gabrielle Dziubla, Richard A. Koup, Michael Pensiero, Leonid Serebryannyy, Marina Caskey, Timothy J. Wilkin ,…
Clinical and Translational Science Published: 27 January 2026
DOI:https://doi.org/10.1111/cts.70488
ABSTRACT
Broadly neutralizing antibodies (BNAb) are capable of neutralizing multiple HIV-1 strains through the targeting of conserved epitopes. This study’s objective was to quantify the pharmacokinetic (PK) parameters describing the distribution and elimination of the BNAb VRC07-523-LS in people with HIV (PWH), and to identify the influence of viral load on VRC07-523-LS elimination. The PK of VRC07-523-LS was assessed in participants with and without HIV after intravenous or subcutaneous administration. A Bayesian strategy was utilized to estimate VRC07-523-LS PK parameters, leveraging a previously published study in adults without HIV. The effects of static viral loads on VRC07-523-LS exposure and time to a target trough serum concentration of 1 mg/L was then evaluated using clinical trial simulations. VRC07-523-LS serum concentrations were described by a two-compartment model with first order absorption from the subcutaneous site. Typical clearance was estimated as 99.3 mL/day, which increased to a maximum of 6.46-fold higher with viremia. Clinical trial simulations without viremia showed that a 700–2100 mg dose of VRC07-523-LS is expected to remain above the IC50 of 0.055 mg/L beyond 52 weeks. With a viral load of 30,000 copies/mL, a 2100 mg dose of VRC07-523-LS is expected to result in 90% of participants having a concentration below 1 mg/L by 18.6 weeks, a decrease of 42 weeks compared to aviremic patients. Mechanistic modeling offers the ability to identify HIV viral load effects on BNAb PK and can improve BNAb dosing, especially with consideration of acute versus maintenance treatment.
Study Highlights
- What is the current knowledge on the topic?
○Broadly neutralizing anti-HIV-1 monoclonal antibodies (BNAbs) are promising therapeutics for both prevention and treatment of HIV. Current generation BNAbs have an increased spectrum of activity and can effectively reduce viral loads in human studies. Further, extended half-life variants of BNAbs could provide year-long coverage with a single dose. - What question did this study address?
○This study provides answers on how HIV-1 viral load affects BNAb dosing requirements and how to optimize the analytical treatment interruption phase of the trial’s design. - What does this study add to our knowledge?
○Evaluation of viral load effects shows increased clearance of BNAbs at high viral loads, necessitating higher potential doses. This study also shows how Bayesian adaptive PK trials of BNAbs can more efficiently identify important analytical treatment interruption time points. - How might this change clinical pharmacology or translational science?
○This study utilized a novel strategy to assess dosing requirements for BNAbs based on clinical circumstance, which could be extended to arbitrarily large BNAb cocktails. Additionally, Bayesian adaptive PK trials provide a strategic opportunity to make sampling and intervention times more efficient and less costly.
