Single Dose Liposomal Amphotericin B works for HIV associated Cryptococcal Meningitis
Cryptococcal meningitis is the most frequent cause of adult meningitis in areas with a high prevalence of human immunodeficiency virus (HIV) and is the second leading cause of HIV-related death worldwide, with the majority of deaths occurring in sub-Saharan Africa. A recent study suggests that single-dose liposomal amphotericin B combined with flucytosine and fluconazole was non-inferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis. The study findings were published in The NEW ENGLAND JOURNAL of MEDICINE on March 24, 2022.
Liposomal amphotericin B is potentially well suited for use in short-course induction treatments of cryptococcal meningitis because it can be given at higher doses owing to a lower incidence of drug-induced toxic effects, has a long tissue half-life and effectively penetrates brain tissue. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. Therefore, Dr Joseph N. Jarvis and his team conducted a study to evaluate the phase 3 AMBITION-Cm trial to evaluate the effect of a single high dose of liposomal amphotericin B on mortality.
The AMBITION-Cm trial is a phase 3 randomized, controlled, noninferiority trial conducted in five African countries. The researchers included 844 HIV-positive adults with cryptococcal meningitis and randomized them to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization–recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The major outcome assessed was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin.
Key findings of the study:
- At 10 weeks, the researchers observed deaths in 101 participants (24.8%) in the liposomal amphotericin B group and 117 (28.7%) in the control group (difference, −3.9 percentage points).
- They noted that the fungal clearance from cerebrospinal fluid was −0.40 log10 colony-forming units (CFU) per millilitre per day in the liposomal amphotericin B group and −0.42 log10 CFU per millilitre per day in the control group.
- They reported that fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%).
The authors concluded, "This trial showed that a single high dose of liposomal amphotericin B given with flucytosine and fluconazole was non-inferior to the current it WHO-recommended standard of care for cryptococcal meningitis and offers a practical treatment for the management for HIV-associated cryptococcal meningitis that is easier to administer and associated with fewer drug-related adverse effects. Continued efforts to ensure access to liposomal amphotericin B and flucytosine are needed to enable the implementation of this treatment."
