Data from: Modelling the evolution of HIV-1 virulence in response to imperfect therapy and prophylaxis

Average HIV-1 virulence appears to have evolved in different directions in different host populations since antiretro- viral therapy first became available, and models predict that HIV drugs can select for either higher or lower virulence, depending on how treatment is administered. However, HIV virulence evolution in response to ‘leaky’ therapy (treat- ment that imperfectly suppresses viral replication) and the use of preventive drugs (pre-exposure prophylaxis) has not been explored. Using adaptive dynamics, we show that higher virulence can evolve when antiretroviral therapy is im- perfectly effective, and that this evolution erodes some of the long-term clinical and epidemiological benefits of HIV treatment. The introduction of pre-exposure prophylaxis greatly reduces infection prevalence, but can further amplify virulence evolution when it, too, is leaky. Increasing the uptake rate of these imperfect interventions increases selection for higher virulence, and can lead to counterintuitive increases in infection prevalence in some scenarios. Although populations almost always fare better with access to interventions than without, untreated individuals could experi- ence particularly poor clinical outcomes when virulence evolves. These findings predict that antiretroviral drugs may have underappreciated evolutionary consequences, but that maximizing drug efficacy can prevent this evolutionary response. We suggest that HIV virulence evolution should be closely monitored as access to interventions continues to improve.自抗逆转录病毒治疗（antiretroviral therapy）首次问世以来，人类免疫缺陷病毒1型（HIV-1）的毒力在不同宿主种群中呈现出差异化演化方向；现有模型预测，HIV药物可根据给药方案筛选出毒力更高或更低的毒株。然而，针对“不完全抑制病毒复制的漏出性治疗”以及暴露前预防（pre-exposure prophylaxis）的HIV毒力演化响应，目前尚未得到相关研究的探索。本研究借助自适应动力学（adaptive dynamics）分析证实，当抗逆转录病毒治疗不完全有效时，毒株毒力可发生演化提升，且该演化过程会削弱HIV治疗长期临床与流行病学收益的一部分。暴露前预防药物的引入可大幅降低人群感染率，但当其同样存在不完全有效性时，会进一步放大毒力的演化进程。提升这类不完全干预措施的服用率，会增强对高毒力毒株的选择压力，在部分场景下甚至会导致感染率出现违背直觉的上升。尽管人群在可获取干预措施时的整体健康水平通常优于无法获取的情况，但当毒力发生演化时，未接受治疗的个体可能会面临尤为糟糕的临床结局。本研究结果预示，抗逆转录病毒药物可能存在此前未被充分认知的演化层面影响，但最大化药物疗效可阻断这类演化响应。我们建议，随着干预措施可及性的持续提升，应密切监测HIV毒力的演化情况。