Primary prevention of invasive cryptococcal disease using fluconazole prophylaxis in HIV infected Ugandans

使用氟康唑预防艾滋病毒感染的乌干达人侵袭性隐球菌病的一级预防

• 批准号: G0601028-E01/1
• 负责人: David Lalloo
• 金额: $ 73.92万
• 依托单位: Liverpool School of Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601028-E01%2F1
• 关键词: Primary; prevention; invasive; cryptococcal; disease

The initial stages of HIV disease are very similar in Africa and resource rich countries, but after AIDS develops, survival is poor in most African countries. This difference is attributed to poor availability of the drugs for treatment of HIV infection (antiretroviral therapy, ART) and inadequate diagnosis and treatment of opportunistic infections. Although there have been major international efforts to increase access to anti-retroviral drugs in Africa, limited infrastructure means that access to ART is still severely restricted: even in areas where ART is available, there are often waiting lists. Prevention of opportunistic infections in the HIV infected is therefore a high priority as it permits healthy survival until ART becomes available. Invasive cryptococcal disease is one of the major causes of life-threatening illness in HIV/AIDS patients in Africa and other parts of the tropics and may cause up to 20% of deaths. Established cryptococcal disease is difficult and costly to treat; it is often a terminal diagnosis in countries with limited resources and access to drugs. Prevention of cryptococcal and other fungal diseases could have a considerable impact upon morbidity and mortality in Africa, especially in those unable to access or who are waiting for ART. Studies in the USA and Europe suggest that regular use of an antifungal drug, fluconazole, may prevent cryptococcal and other fungal diseases. Similar studies have not been done in Africa but the higher incidence of cryptococcal disease in tropical settings means that there could be an even greater impact on morbidity and mortality. Generic fluconazole is now freely and cheaply available in Africa, meaning that the strategy of using fluconazole to prevent cryptococcal disease has become increasingly attractive, especially as established disease is so difficult to treat.This study has already commenced in partnership with TASO (the AIDS Support Organisation), the leading HIV care organisation in Uganda. 669 participants have been enrolled into a double blind study to compare the efficacy and safety of fluconazole with placebo, measuring cryptococcal disease and mortality. However, the incidence of cryptococcal disease has been lower than anticipated due to the extensive use of ART at the study site and screening out of participants who are most at risk. We are now seeking an extension to this study allowing enrolment of a further 870 patients thus ensuring that the study is sufficiently powerful to enable us to make firm conclusions about the benefit of this intervention.

在非洲和资源丰富的国家，艾滋病毒疾病的最初阶段非常相似，但是在艾滋病发展之后，大多数非洲国家的生存率很差。这种差异归因于药物可用于治疗HIV感染（抗逆转录病毒疗法，ART）以及机会性感染的诊断和治疗不足的药物可用性。尽管国际上已经做出了重大努力，以增加非洲的抗逆转录病毒药物的机会，但有限的基础设施意味着仍然受到严格限制：即使在可用的艺术区域，也经常有等待名单。因此，预防受HIV感染的机会性感染是一个高度优先事项，因为它允许健康的生存，直到可用。侵入性加密局疾病是非洲和热带地区其他部位艾滋病毒/艾滋病患者威胁生命的疾病的主要原因之一，可能会导致多达20％的死亡。建立的隐球菌疾病很难治疗；它通常是资源有限且获得毒品的国家的最终诊断。预防隐球菌和其他真菌疾病可能会对非洲的发病率和死亡率产生重大影响，尤其是那些无法获得或正在等待艺术的人。在美国和欧洲的研究表明，定期使用抗真菌药物氟康唑可能会防止隐球菌和其他真菌疾病。在非洲尚未进行类似的研究，但是在热带环境中加密世界疾病的发病率更高意味着可能对发病率和死亡率产生更大的影响。现在，通用氟康唑现在在非洲自由且便宜地可用，这意味着使用氟康唑防止隐球菌疾病的策略变得越来越有吸引力，尤其是因为既定疾病很难治疗。 669名参与者已被招募到一项双盲研究中，以将氟康唑与安慰剂的疗效和安全性与安慰剂进行比较，以测量隐球菌疾病和死亡率。但是，由于研究地点广泛使用ART并筛选出最大风险的参与者，因此隐球菌疾病的发生率一直低于预期。现在，我们正在寻求这项研究的扩展，允许进一步入学870名患者，从而确保该研究足够强大，使我们能够对这种干预的好处得出确定的结论。