Tebas Pablo
Division of Infectious Diseases, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Curr HIV/AIDS Rep. 2025 May 27;22(1):34. doi: 10.1007/s11904-025-00744-1.
Broadly neutralizing antibodies (bNAbs) represent a novel approach to HIV treatment, prevention, and cure strategies. As research advances, the clinical application of bNAbs continues to evolve. This review explores the potential role of bNAbs in HIV management, addressing their mechanisms of action, current limitations, and future directions.
Recent studies have demonstrated that bNAbs can effectively neutralize a broad range of HIV strains by targeting conserved epitopes on the viral envelope. Clinical trials have shown that bNAb combinations can maintain viral supression in the absence of antiretroviral therapy (ART), though pre-existing resistance remains a major challenge. Strategies such as Fc engineering and alternative delivery mechanisms (e.g., AAV, mRNA, DNA) are being explored to enhance bNAb efficacy and durability. Despite promising data, bNAbs have not yet demonstrated superior effectiveness compared to existing ART or pre-exposure prophylaxis (PrEP) options. While bNAbs offer exciting possibilities for long-acting HIV therapy, their widespread use is limited by logistical challenges, high production costs, and pre-existing viral resistance. The future of bNAbs may lie in combination strategies with small-molecule antiretrovirals in maintenance strategies, genetic delivery systems, and vaccine-based approaches to induce endogenous bNAb production. Further research is needed to refine these strategies and determine the optimal role of bNAbs in HIV care.
广泛中和抗体（bNAbs）代表了一种用于HIV治疗、预防和治愈策略的新方法。随着研究的进展，bNAbs的临床应用不断发展。本综述探讨了bNAbs在HIV管理中的潜在作用，阐述了其作用机制、当前局限性和未来方向。
最近的研究表明，bNAbs可通过靶向病毒包膜上的保守表位有效中和多种HIV毒株。临床试验表明，在没有抗逆转录病毒疗法（ART）的情况下，bNAb组合可维持病毒抑制，尽管预先存在的耐药性仍然是一个主要挑战。正在探索诸如Fc工程和替代递送机制（如腺相关病毒、信使核糖核酸、脱氧核糖核酸）等策略，以提高bNAb的疗效和持久性。尽管有令人鼓舞的数据，但与现有的ART或暴露前预防（PrEP）方案相比，bNAbs尚未显示出更高的有效性。虽然bNAbs为长效HIV治疗提供了令人兴奋的可能性，但其广泛应用受到后勤挑战、高生产成本和预先存在病毒耐药性的限制。bNAbs的未来可能在于与小分子抗逆转录病毒药物联合用于维持策略、基因递送系统以及基于疫苗的方法以诱导内源性bNAb产生。需要进一步研究来完善这些策略，并确定bNAbs在HIV治疗中的最佳作用。
