Seden Kay, Gibbons Sara, Marzolini Catia, Schapiro Jonathan M, Burger David M, Back David J, Khoo Saye H
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel, Basel, Switzerland.
PLoS One. 2017 Mar 23;12(3):e0173509. doi: 10.1371/journal.pone.0173509. eCollection 2017.
In all settings, there are challenges associated with safely treating patients with multimorbidity and polypharmacy. The need to characterise, understand and limit harms resulting from medication use is therefore increasingly important. Drug-drug interactions (DDIs) are prevalent in patients taking antiretrovirals (ARVs) and if unmanaged, may pose considerable risk to treatment outcome. One of the biggest challenges in preventing DDIs is the substantial gap between theory and clinical practice. There are no robust methods published for formally assessing quality of evidence relating to DDIs, despite the diverse sources of information. We defined a transparent, structured process for developing evidence quality summaries in order to guide therapeutic decision making. This was applied to a systematic review of DDI data with considerable public health significance: HIV and malaria.
This was a systematic review of DDI data between antiretrovirals and drugs used in prophylaxis and treatment of malaria. The data comprised all original research in humans that evaluated pharmacokinetic data and/or related adverse events when antiretroviral agents were combined with antimalarial agents, including healthy volunteers, patients with HIV and/or malaria, observational studies, and case reports. The data synthesis included 36 articles and conference presentations published via PubMed and conference websites/abstract books between 1987-August 2016. There is significant risk of DDIs between HIV protease inhibitors, or NNRTIs and artemesinin-containing antimalarial regimens. For many antiretrovirals, DDI studies with antimalarials were lacking, and the majority were of moderate to very low quality. Quality of evidence and strength of recommendation categories were defined and developed specifically for recommendations concerning DDIs.
There is significant potential for DDIs between antiretrovirals and antimalarials. The application of quality of evidence and strength of recommendation criteria to DDI data is feasible, and allows the assessment of DDIs to be robust, consistent, transparent and evidence-based.
在所有医疗环境中，安全治疗患有多种疾病和使用多种药物的患者都存在挑战。因此，表征、理解和限制药物使用所导致危害的需求日益重要。药物相互作用（DDIs）在服用抗逆转录病毒药物（ARVs）的患者中很常见，如果不加以管理，可能会对治疗结果构成相当大的风险。预防药物相互作用的最大挑战之一是理论与临床实践之间存在巨大差距。尽管信息来源多样，但尚未发表用于正式评估与药物相互作用相关证据质量的可靠方法。我们定义了一个透明、结构化的过程来制定证据质量总结，以指导治疗决策。这一过程应用于对具有重大公共卫生意义的药物相互作用数据进行系统评价：艾滋病毒和疟疾。
这是一项关于抗逆转录病毒药物与用于预防和治疗疟疾的药物之间药物相互作用数据的系统评价。数据包括所有评估抗逆转录病毒药物与抗疟药物联合使用时药代动力学数据和/或相关不良事件的人体原始研究，包括健康志愿者、艾滋病毒和/或疟疾患者、观察性研究和病例报告。数据综合包括1987年至2016年8月期间通过PubMed以及会议网站/摘要书籍发表的36篇文章和会议报告。艾滋病毒蛋白酶抑制剂或非核苷类逆转录酶抑制剂与含青蒿素的抗疟方案之间存在显著的药物相互作用风险。对于许多抗逆转录病毒药物，缺乏与抗疟药物的药物相互作用研究，而且大多数研究质量为中等至非常低。证据质量和推荐强度类别是专门为有关药物相互作用的推荐定义和制定的。
抗逆转录病毒药物与抗疟药物之间存在显著的药物相互作用可能性。将证据质量和推荐强度标准应用于药物相互作用数据是可行的，并且能够使药物相互作用的评估稳健、一致、透明且基于证据。
