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I recently completed a €10 million EDCTP / Wellcome Trust / MRC / DFID Joint Global Health Trials co-funded project running a multi-centre randomised trial investigating single-dose liposomal amphotericin treatment for HIV-associated cryptococcal meningitis (the AMBITION-cm Trial). The trial consortium involved partners in Africa (University of Cape Town; University of Zimbabwe; Botswana Harvard Partnership; Malawi-Liverpool Wellcome Trust Centre, Blantyre and the University of North Carolina Project, Lilongwe, Malawi; and the Infectious Diseases Institute, Makerere University, Uganda) and Europe (St. George's University of London; University of Liverpool; Liverpool School of Tropical Medicine; and Institut Pasteur Paris). In addition to the clinical trial, the project included PK/PD analyses, an economic evaluation, and numerous sub-studies, as well as a considerable training and capacity building component. The findings were published in the NEJM in March 2022, and WHO guidelines were updated to include the new strategy as recommended first line treatment in April 2022.
Building on the trial, my NIHR professorship funds translational studies aimed at improving understanding of the aetiology of meningitis in high HIV-prevalence settings, developing and testing novel diagnostics for central nervous system infections, and exploring host genetic susceptibility to cryptococcal meningitis. A CDC collaborative award is supporting the roll-out of the AMBITION-cm regimen widely across Africa. And the NIHR Global Health Group, co-led with Professor Nelesh Govender at the NICD in Johannesburg, South Africa, is applying the lessons learnt through the AMBITION-cm trial to other HIV-associated fungal infections of public health importance including histoplasmosis, PCP, and talaromycosis.