How applicable is the single-dose AMBITION regimen for HIV–associated cryptococcal meningitis to high-income settings?

The AMBITION-cm phase III randomized controlled trial, conducted in east and southern Africa, showed that a single high dose (10 mg/kg) of liposomal amphotericin B, given with an optimized oral backbone of fluconazole and flucytosine, was non-inferior to the World Health Organization (WHO)-recommended regimen of seven days of amphotericin B deoxycholate plus flucytosine for treatment of HIV-associated cryptococcal meningitis, and has been incorporated into updated WHO treatment guidelines. We believe the trial findings also have important implications for the treatment of HIV-associated cryptococcal meningitis in high-income settings. We advance the arguments, supported by evidence where available, that the AMBITION-cm study regimen is likely to be (i) as fungicidal as the currently recommended 14-day liposomal amphotericin based treatments, (ii) better tolerated with fewer adverse effects, and (iii) confer significant economic and practical benefits, therefore should be included as a treatment option in guidance for HIV-associated cryptococcal treatment in high-income country settings.