How Applicable Is the Single-Dose AMBITION Regimen for Human Immunodeficiency Virus–Associated Cryptococcal Meningitis to High-Income Settings?

Abstract

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.

Less Is More? Two Cases of Cryptococcosis Treated Using Single-dose Liposomal Amphotericin B as Part of Induction Therapy in Solid Organ Transplant Recipients

“…A shorter duration of l -AmB and reduced adverse effects may lead to fewer intravenous administrations, shorter hospitalization, and decreased adverse event monitoring, with cost savings throughout. 6 , 15 The AMBITION regimen was cost-effective among PLWH in sub-Saharan African countries, with a low incremental cost-effectiveness ratio of $80 ($15–275) (USD) per life-year saved. 16 A substudy of the AMBITION trial interviewed patients, healthcare providers, and researchers, who expressed a preference for the AMBITION regimen.…”

Infectious Diseases Physician Management of Cryptococcal Meningitis in North America—Is Single High-Dose Liposomal Amphotericin B Being Used?

“…This survey gives helpful insight into treatment decisions for a subset of ID physicians practicing primarily in the United States [ 11 ]. There are some physicians utilizing the AMBITION-cm regimen, but use is not widespread.…”

“…The applicability of the AMBITION-cm regimen to high-income settings and in patients without HIV is not uniformly agreed upon. Although widespread use is advocated for by some based on its equivalent quantitative antifungal activity, lower cost, and lower toxicity, its uptake in the United States is unknown [ 11 ]. In the context of the AMBITION-cm trial's publication in March 2022 [ 8 ], we aimed to characterize preferred treatment regimens for cryptococcal meningitis in varied patient populations among practicing infectious diseases physicians in order to gain insight on perception and potential barriers to uptake.…”

Safety of Single High-Dose Liposomal Amphotericin B for Induction Treatment of Cryptococcal Meningitis and Histoplasmosis in People With HIV: A Systematic Review and Meta-analysis

“…Our findings may also have implications for using single high-dose LAmB in induction therapy in well-resourced contexts, where there is growing advocacy for this dosing strategy [ 17 ]. One limiting factor is the absence of a large randomized clinical trial in a high-income country comparing induction therapy involving single high-dose LAmB with existing standard of care using longer duration and a higher total dose of LAmB for HIV-associated cryptococcosis [ 18 ] or histoplasmosis [ 19 ].…”