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.

广泛中和抗体是治疗和预防 HIV-1 感染的有希望的候选者。这种抗体可以暂时抑制受感染个体的病毒载量；然而，病毒经常被进化出抵抗力的逃逸突变体反弹。在本文中，我们使用最近一项临床试验的体内数据绘制了 HIV-1 与广泛中和抗体相互作用的适应性模型。我们确定了两个适合度因素，抗体剂量和病毒载量，它们决定了不同宿主之间可重复的病毒繁殖率。该模型成功地预测了抗体治疗过程中 HIV-1 的逃逸动力学，包括敏感菌株和耐药菌株之间的特征频率转换。这种营业额受剂量依赖的健康排名控制，源于抗体抗性与其在无药物生长中的附带成本之间的进化权衡。我们的分析表明，耐药性-成本权衡曲线可作为在存在耐药性进化的情况下衡量抗体性能的指标。