Clinical trials of broadly neutralizing monoclonal antibodies in people living with HIV - a review.

Abstract

Introduction: HIV-1 remains a major global health challenge, impacting approximately 39 million people worldwide. Although antiretroviral therapy has substantially reduced HIV incidence and enhanced the quality of life for those living with HIV, adherence difficulties, limited access, and persistent stigma continue to exacerbate the disease burden. A curative or long-term immunological control strategy without continuous medication would significantly advance pandemic management. In the 2010s, technological progress led to the development of a new generation of broadly neutralizing antibodies (bNAbs) with improved potency and breadth, targeting conserved regions of the HIV-1 envelope and facilitating viral neutralization and clearance.

Methods: This review evaluates the clinical outcomes and potential of bNAbs in people living with HIV, summarizing findings from a review of 154 registered trials, of which 62 met the inclusion criteria focusing on adult PLWH.

Results: Early trials confirmed bNAbs' safety but revealed transient and limited viral suppression, often due to viral escape. Second-generation bNAbs like VRC01 and 3BNC117, as well as combination therapies such as 3BNC117 with 10-1074, extended viral suppression but continued to face resistance challenges.

Conclusion: More recent trials that paired bNAbs with latency-reversing agents or combined multiple bNAbs demonstrated promising results, including delayed viral rebound and enhanced CD8 + T-cell responses. While bNAbs show potential as an adjunct or alternative to ART, obstacles such as viral resistance, high production costs, and scalability must be addressed. Continued research is crucial to developing more potent, durable, and affordable bNAbs for sustainable HIV treatment and potential remission.