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 findings have already had an impact on policy. In April 2022, WHO issued a rapid guidance update that strongly recommended use of single high-dose amphotericin B for the treatment of cryptococcal meningitis in people living with HIV.
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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, found that treatment responses to single-dose amphotericin B matched those to amphotericin B deoxycholate and flucytosine, and significantly fewer serious adverse reactions were seen.
The AMBITION-cm study has shown that a simplified treatment for cryptococcal meningitis, one of the major causes of death of people living with HIV, is as good as existing treatments – and could potentially generate cost savings as well.
Simplified treatment for a key opportunistic infection