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 an in vivo fitness landscape of HIV-1 interacting with broadly neutralizing antibodies, using 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 tradeoff between antibody resistance and its collateral cost in drug-free growth. Our analysis suggests resistance-cost tradeoff curves as a measure of antibody performance in the presence of resistance evolution.

中文翻译：

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从广泛中和的抗体预测HIV-1的体内逃逸动态

广泛中和的抗体有望成为治疗和预防HIV-1感染的候选药物。这类抗体可以暂时抑制受感染个体的病毒载量。但是，病毒通常会通过已产生抗性的逃避突变体反弹。在本文中，我们绘制了一个体内HIV-1与广泛中和抗体相互作用的健康状况，使用最近的一项临床试验数据。我们确定了两个适应性因子，抗体剂量和病毒载量，它们决定了不同宿主之间可再现的病毒繁殖率。该模型成功预测了抗体治疗过程中HIV-1的逃逸动态，包括敏感菌株和耐药菌株之间的特征频率转换。此周转率由剂量依赖性适应性等级决定，该排名是抗体抗性与其无药生长附带成本之间的进化折衷。我们的分析表明，在存在抗性进化的情况下，抗性成本折衷曲线可作为衡量抗体性能的指标。