Current methods for detecting and assessing HIV-1 antibody resistance
Stanley Odidika1,2,3, Martin Pirkl3,4, Thomas Lengauer3,4,5
1Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Frontiers in Immunology
|January 21, 2025
Summary
Broadly neutralizing antibodies (bNAbs) show promise for HIV treatment, but HIV-1 antibody resistance (HIVAR) hinders their use. Understanding and detecting HIVAR is crucial for developing effective HIV therapies and vaccines.
Area of Science:
- Immunology
- Virology
- Drug Development
Background:
- Antiretroviral therapy (ART) remains standard for HIV but faces challenges with adherence and side effects, with millions of new infections and deaths annually.
- Broadly neutralizing antibodies (bNAbs) offer a promising alternative for HIV-1 treatment and prevention, demonstrating potential in clinical trials.
- HIV-1 antibody resistance (HIVAR), driven by variants in HIV-1 envelope glycoproteins, is a significant barrier to bNAb efficacy and vaccine development.
Purpose of the Study:
- To review current methods for detecting, characterizing, and predicting HIV-1 antibody resistance (HIVAR).
- To highlight the importance of understanding HIVAR for the clinical application of broadly neutralizing antibodies (bNAbs) in HIV treatment and prevention.
- To identify gaps in current HIVAR detection assays and define resistance for novel bNAbs.
Main Methods:
- Structural analysis of antibody-HIV-1 Env complexes to identify critical viral residues for neutralization.
- In vitro viral neutralization and adaptation assays to assess bNAb susceptibility based on envelope sequence.
- In vivo studies in animal models and clinical trials to observe the emergence of HIVAR variants.
Main Results:
- Structural, in vitro, and in vivo studies have identified and validated HIVAR for most available bNAbs.
- Emergence of escape variants to bNAb treatments has been observed in both animal models and human clinical trials.
- Despite progress, defined assays for HIVAR detection in patients are lacking, and resistance profiles for some novel bNAbs remain undefined.
Conclusions:
- HIVAR is a critical challenge for the clinical use of bNAbs and the development of effective HIV vaccines.
- Continued research into structural, in vitro, and in vivo methods is essential for understanding and overcoming HIVAR.
- Development of standardized diagnostic assays for HIVAR detection is urgently needed to guide bNAb therapy and future vaccine strategies.
