Optimizing antifungal therapy for HIV-associated cryptococcal meningitis in Africa

我们将在非洲测试抗真菌药物替代剂量和组合治疗隐球菌性脑膜炎的活性。隐球菌性脑膜炎是非洲艾滋病毒和艾滋病患者中一种非常常见的感染和死亡原因。目前的药物治疗需要很长时间才能控制感染。此外，治疗方法的改进一直缓慢，因为传统的治疗试验需要许多患者，因此进行起来缓慢而昂贵。然而，我们现在已经开发出一种新方法，通过测量引起感染的生物体的杀伤率，在少数患者中测试新药物组合和剂量的活性。使用这种方法，我们将在患者身上测试实验室测试和动物实验表明更有效、更安全的替代药物组合和剂量。将进行平行研究：优化静脉注射药物两性霉素B和口服药物氟康唑的剂量和组合。这些研究的结果将用于确定如何最好地使用目前可用的药物，并为进一步的试验选择最佳组合，以确定新的组合是否可以减少由这种感染引起的死亡人数。

We will test the activity of alternative doses and combinations of antifungal drugs in the treatment of cryptococcal meningitis in Africa. Cryptococcal meningitis is a very common infection and cause of death in patients with HIV and AIDS in Africa. Current drug treatment takes a long time to control the infection. In addition, improvements in treatment have been slow because traditional trials of treatment need many patients and are therefore slow and expensive to undertake. However, we have now developed a new way to test the activity of new drug combinations and dosages in small numbers of patients, by measuring the rate of killing of the organism causing the infection. Using this method, we will test alternative drug combinations and dosages in patients that laboratory testing and animal experiments have suggested will be more active and also safe. Parallel studies will be done: to optimize doses and combinations with the intravenous drug, amphotericin B, and with the oral drug, fluconazole. The results of the studies will be used to determine how best to use the drugs that are currently available, and to select the best combinations for further trials to find out if the new combinations can reduce the number of deaths caused by this infection.