AMBITION-cm study wins the 2023 European Hector Research Award in HIV

23 October 2023

EDCTP congratulates the AMBITION-cm study team, led by Professor Joe Jarvis at the London School of Hygiene and Tropical Medicine, on winning the 2023 European Hector Research Award in HIV. This prize for European HIV research, given by the H.W. & J. Hector Foundation, Weinheim, recognises the best scientific achievements in HIV research. The AMBITION-cm study was funded by EDCTP in collaboration with the UK Medical Research Council, UK Department of International Development (now FCDO) and Wellcome, and with funding from the Swedish International Development Cooperation Agency (SIDA).

The ABITION-cm study

Cryptococcus, a fungal pathogen, can infect the brain, causing a potentially fatal form of meningitis. It is a particular danger to people living with HIV – globally, it is the second most common HIV-related cause of death, and most deaths occur in sub-Saharan Africa.

The recommended treatment for cryptococcal meningitis has been a week-long course of two drugs, amphotericin B deoxycholate and flucytosine. However, the first of these can trigger damaging adverse reactions, so patients need careful monitoring, which is not always possible in low-resource settings.

The AMBITION-cm phase III trial evaluated a simpler alternative approach, based on a single dose of amphotericin B in a liposomal formulation. This has the advantage of being less toxic, so it can be used at higher doses, has a long half-life, and readily enters the brain. The trial, which recruited more than 800 patients in five African countries, showed that a single, high-dose of liposomal amphotericin B was as good as the WHO recommended standard of care for HIV-associated cryptococcal meningitis and much easier to give, requiring just one intravenous infusion compared to 7 days with standard therapy. The liposomal amphotericin B regimen was also associated with significantly fewer drug related effects such as anaemia, electrolyte abnormalities and intravenous line site infections.

Furthermore, the AMBITION-cm trial team has developed costing tools for cryptococcal management in Botswana, Malawi, South Africa, Uganda and Zimbabwe, and shown that the new regimen is likely to be highly cost-effective. As fewer adverse reactions will be seen and hospital stays are likely to be shorter, it could even lead to cost savings. In addition, in consultations with trial participants and healthcare staff, the new regimen was positively received and thought likely to reduce clinical workload. The AMBITION-cm trial results led to updated WHO guidelines to recommend this simpler, safer treatment for cryptococcal disease in people living with HIV.