LAUSR

Significance Broadly neutralizing antibodies (bnAbs) show promise for antibody-mediated prevention or treatment of HIV-1 infection. Recent clinical trials, however, indicate that the virus can evolve resistance mutations that escape neutralization by bnAbs. Here, we establish a fitness model for the escape dynamics of HIV in humans. We show that this model can be applied universally across different human hosts, providing a proof of principle that the in vivo response of HIV to bnAb therapies is predictable. Our analysis identifies a fitness trade-off in viral evolution that can inform antibody design and therapy protocols. 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.