Predicting in vivo escape dynamics of HIV-1 from a broadly neutralizing antibody

Proc Natl Acad Sci U S A. 2021 Jul 27;118(30):e2104651118. doi: 10.1073/pnas.2104651118.


Broadly neutralizing antibodies are promising candidates for treatment and prevention of HIV-1 infections. Such antibodies can temporarily suppress viral load in infected individuals; however, the virus often rebounds by escape mutants that have evolved resistance. In this paper, we map a fitness model of HIV-1 interacting with broadly neutralizing antibodies using in vivo data from a recent clinical trial. We identify two fitness factors, antibody dosage and viral load, that determine viral reproduction rates reproducibly across different hosts. The model successfully predicts the escape dynamics of HIV-1 in the course of an antibody treatment, including a characteristic frequency turnover between sensitive and resistant strains. This turnover is governed by a dosage-dependent fitness ranking, resulting from an evolutionary trade-off between antibody resistance and its collateral cost in drug-free growth. Our analysis suggests resistance-cost trade-off curves as a measure of antibody performance in the presence of resistance evolution.

Keywords: HIV-1; broadly neutralizing antibodies; escape dynamics; evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Broadly Neutralizing Antibodies / physiology*
  • Dose-Response Relationship, Immunologic
  • HIV Antibodies / therapeutic use*
  • HIV Infections / therapy*
  • HIV-1 / physiology*
  • Humans
  • Immune Evasion*
  • Models, Biological*


  • Broadly Neutralizing Antibodies
  • HIV Antibodies