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REVIEW article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1443377
This article is part of the Research Topic Viral Surface Spikes: Host Cell Entry, Immune Responses and Evasion, and Implications for Viral Infection, Inhibition and Rebound View all articles

Current methods for detecting and assessing HIV-1 antibody resistance

Provisionally accepted
Stanley Odidika Stanley Odidika Martin Pirkl Martin Pirkl Thomas Lengauer Thomas Lengauer Philipp Schommers Philipp Schommers *
  • University of Cologne, Cologne, North Rhine-Westphalia, Germany

The final, formatted version of the article will be published soon.

    Antiretroviral therapy is the standard treatment for HIV, but it requires daily use and can cause side effects. Despite being available for decades, there are still 1.5 million new infections and 700,000 deaths each year, highlighting the need for better therapies. Broadly neutralizing antibodies (bNAbs), which are highly active against HIV-1, represent a promising new approach and clinical trials have demonstrated the potential of bNAbs in the treatment and prevention of HIV-1 infection. However, HIV-1 antibody resistance (HIVAR) due to variants in the HIV-1 envelope glycoproteins (HIV-1 Env) is not well understood yet and poses a critical problem for the clinical use of bNAbs in treatment. HIVAR also plays an important role in the future development of an HIV-1 vaccine, which will require elicitation of bNAbs to which the circulating strains are sensitive. In recent years, a variety of methods have been developed to detect, characterize and predict HIVAR. Structural analysis of antibody-HIV-1 Env complexes has provided insight into viral residues critical for neutralization, while testing of viruses for antibody susceptibility has verified the impact of some of these residues. In addition, in vitro viral neutralization and adaption assays have shaped our understanding of bNAb susceptibility based on the envelope sequence. Furthermore, in vivo studies in animal models have revealed the rapid emergence of escape variants to mono- or combined bNAb treatments. Finally, similar variants were found in the first clinical trials testing bNAbs for the treatment of HIV-1-infected patients. These structural, in vitro, in vivo and clinical studies have led to the identification and validation of HIVAR for almost all available bNAbs. However, defined assays for the detection of HIVAR in patients are still lacking and for some novel, highly potent and broad-spectrum bNAbs, HIVAR have not been clearly defined. Here, we review currently available approaches for the detection, characterization and prediction of HIVAR.

    Keywords: HIV, antibody, Mutation, aids, bNAbs, broadly neutralizing antibodies

    Received: 03 Jun 2024; Accepted: 10 Dec 2024.

    Copyright: © 2024 Odidika, Pirkl, Lengauer and Schommers. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Philipp Schommers, University of Cologne, Cologne, 50923, North Rhine-Westphalia, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.