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.

自抗逆转录病毒疗法（antiretroviral therapy）首次问世以来，HIV-1的平均毒力似乎在不同宿主群体中呈现出差异化演化方向；现有模型预测，HIV药物对毒力的选择压力可能偏向更高或更低水平，具体取决于治疗方案的实施方式。然而，针对‘渗漏性治疗’（即无法完全抑制病毒复制的治疗手段）以及暴露前预防药物（pre-exposure prophylaxis，PrEP）使用所引发的HIV毒力演化，目前尚未有相关研究探讨。本研究借助适应性动力学（adaptive dynamics）开展分析，结果表明：当抗逆转录病毒疗法的抑制效果不完全时，HIV毒力会向更高水平演化；这种演化会削弱HIV治疗在长期临床及流行病学层面的部分获益。暴露前预防的推广可大幅降低感染患病率，但如果该预防手段同样存在渗漏性，则会进一步加剧毒力的演化进程。提升这类不完全干预手段的覆盖率会增强对更高毒力毒株的选择压力，在部分场景下甚至会引发与直觉相悖的感染患病率上升。尽管相较于未采取干预措施的情况，人群在使用干预手段后整体境况通常会有所改善，但当毒力发生演化时，未接受治疗的个体可能会面临格外糟糕的临床结局。本研究结果表明，抗逆转录病毒药物可能存在尚未被充分认知的演化层面影响，但通过最大化药物疗效可有效阻断这类演化反应。我们建议，随着HIV干预手段的可及性不断提升，应密切监测HIV毒力的演化情况。