WHO Collaborating Centre for Reference and Research on Influenza at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Biomedicine Discovery Institute & Department of Microbiology, Monash University, Clayton, Australia.
PLoS Pathog. 2022 May 12;18(5):e1010481. doi: 10.1371/journal.ppat.1010481. eCollection 2022 May.
Antiviral drugs are an important measure of control for influenza in the population, particularly for those that are severely ill or hospitalised. The neuraminidase inhibitor (NAI) class of drugs, including oseltamivir, have been the standard of care (SOC) for severe influenza illness for many years. The approval of drugs with novel mechanisms of action, such as baloxavir marboxil, is important and broadens potential treatment options for combination therapy. The use of antiviral treatments in combination for influenza is of interest; one potential benefit of this treatment strategy is that the combination of drugs with different mechanisms of action may lower the selection of resistance due to treatment. In addition, combination therapy may become an important treatment option to improve patient outcomes in those with severe illness due to influenza or those that are immunocompromised. Clinical trials increasingly evaluate drug combinations in a range of patient cohorts. Here, we summarise preclinical and clinical advances in combination therapy for the treatment of influenza with reference to immunocompromised animal models and clinical data in hospitalised patient cohorts where available. There is a wide array of drug categories in development that have also been tested in combination. Therefore, in this review, we have included polymerase inhibitors, monoclonal antibodies (mAbs), host-targeted therapies, and adjunctive therapies. Combination treatment regimens should be carefully evaluated to determine whether they provide an added benefit relative to effectiveness of monotherapy and in a variety of patient cohorts, particularly, if there is a greater chance of an adverse outcome. Safe and effective treatment of influenza is important not only for seasonal influenza infection, but also if a pandemic strain was to emerge.
抗病毒药物是控制流感在人群中传播的重要手段，特别是对于那些病情严重或住院的患者。神经氨酸酶抑制剂（NAI）类药物，包括奥司他韦，多年来一直是严重流感疾病的标准治疗方法（SOC）。具有新型作用机制的药物（如巴洛沙韦）的批准非常重要，拓宽了联合治疗的潜在治疗选择。联合使用抗病毒药物治疗流感具有重要意义；这种治疗策略的一个潜在好处是，不同作用机制的药物联合使用可能会降低因治疗而产生耐药性的选择。此外，联合治疗可能成为改善因流感或免疫功能低下而病情严重的患者预后的重要治疗选择。临床试验越来越多地在一系列患者群体中评估药物联合治疗。在这里，我们参考免疫功能低下动物模型和住院患者队列中的临床数据，总结了联合治疗流感的临床前和临床进展。有许多正在开发的药物类别也已经进行了联合测试。因此，在本综述中，我们包括了聚合酶抑制剂、单克隆抗体（mAbs）、宿主靶向疗法和辅助疗法。联合治疗方案应仔细评估，以确定它们相对于单药治疗的有效性是否提供了额外的益处，并且在各种患者群体中，如果出现不良后果的可能性更大，则更应如此。安全有效的流感治疗不仅对季节性流感感染很重要，而且如果出现大流行株也很重要。
