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Project Topic
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The AMBITION-cm grant is supporting a number of activities aimed at improving outcomes for patients with advanced HIV who are diagnosed with cryptococcal meningitis. Cryptococcal meningitis is a fungal infection of the brain which affects approximately 230,000 people and accounts for 180,000 HIV-related deaths every year, the majority of which occur in sub-Saharan Africa. The AMBITION consortium have been awarded a grant of just under €10 million to conduct a clinical trial that aims to develop a clinically-effective, safe and cost-effective alternative to the current standard treatment, and to conduct additional research to further our scientific understanding of this infection and build research capacity in the region. The grant commenced in January 2017 and will run until December 2020. The AMBITION consortium is composed of researchers from European organisations (The London School of Hygiene and Tropical Medicine, St George’s University, London, University of Liverpool, Liverpool School of Tropical Medicine and Institut Pasteur, Paris) and African institutions (the Botswana-Harvard AIDS Institute Partnership, the Malawi-Liverpool Wellcome Trust Clinical Research Programme in Blantyre, Malawi; the University of North Carolina Project in Lilongwe, Malawi; the University of Cape Town, South Africa; Infectious Diseases Institute, Uganda and the University of Zimbabwe). Each African site is currently enrolling patients into the largest cryptococcal meningitis trial ever conducted, with an overall recruitment target of 850 patients. The trial will compare the standard treatment - 7 days of intravenous medication, associated with numerous side-effects - to a single high-dose of a similar, but less toxic form of the drug regimen. During the second year of the grant the consortium have opened recruitment at seven hospitals across our six sites, and are meeting recruitment targets. As of late February, we have recruited 159 participants. This is testament to the hard work of our research teams but also demonstrates that cryptococcal meningitis remains a significant public health issue in Sub-Saharan Africa. By evaluating the safety and effectiveness of this trial regimen we hope to effect an important change to international treatment guidelines. In addition, we are undertaking an extensive cost-effectiveness study which aims to demonstrate the financial appeal and viability of this regimen. We are also conducting various scientific sub-studies to develop new diagnostics for cryptococcal meningitis, to learn more about the pharmacology of the treatments and to deepen our understanding of the immunology and genetics of the pathogen and its impact on individuals. Training and capacity building are a key component of the AMBITION project and in 2018 we hosted two international training courses. The first was a five-day Clinical Trials and Good Clinical Practice course which took place in March 2018 in Gaborone, Botswana. The course was attended by individuals from each of the recruiting sites as well as a broader research audience based in Botswana, and aimed to increase participants’ understanding of how trials are conceived, designed and conducted. The second was a five-day Medical Mycology course hosted by the University of Cape Town, attended by African colleagues from our recruiting sites as well as physicians and laboratory scientists from all over the continent. Lectures and practical laboratory sessions were delivered by world-leading mycology experts. The consortium are planning further courses for 2019 and 2020 which will focus on the important skills of data analysis, scientific writing and grant applications. One MSc studentship was awarded in 2018 to a study doctor from Uganda who is currently undertaking an MSc in the Immunology of Infectious Diseases at the London School of Hygiene & Tropical Medicine. Another two MSc studentships will be awarded in early 2019. To build on the expertise of the consortium and the resources and frameworks created within this large study we have formed the African Meningitis Network (AMNET). AMNET brings together experienced researchers to develop grant applications and conceptualise future clinical trials that can continue to address important questions about all forms of meningitis which are common in Sub-Saharan African. AMNET have completed several research activities to demonstrate the research capacity and public health need for further meningitis trials in the future. Our hope is that in 2019 AMNET will start to define specific angles for future meningitis research and begin to plan potential grant applications. We look forward to recruiting more patients over the next year and to working towards our goal of ensuring universal access to affordable, safe and effective treatment for HIV-associated cryptococcal meningitis by providing a practical first-line treatment option with the potential to prevent many thousands of deaths.
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