Single High-Dose Liposomal Amphotericin B Effectively Treats HIV-Associated Cryptococcal Meningitis

Cryptococcus neoformans
Cryptococcus neoformans
Single high-dose liposomal amphotericin B treatment was non-inferior to standard dose 14-day amphotericin B treatment in HIV-associated cryptococcal meningitis.

Short course, high dose liposomal amphotericin B (L-AmB) in combination with high dose fluconazole effectively treats HIV-associated cryptococcal meningitis, according to a study recently published in Clinical Infectious Diseases.

This open label phase-II randomized non-inferiority trial included 80 adults infected with HIV presenting with the first episode of cryptococcal meningitis. Patients were randomly assigned to receive either a single dose of L-AmB 10 mg/kg on day 1, 2 doses as L-AmB 10 mg/kg on day 1 and 5mg/kg on day 3, 3 doses as L-AmB 10 mg/kg on day 1 and 5 mg/kg on days 3 and day 7, and L-AmB 3 mg/kg for 14 days (control).

The pre-specified primary endpoint was the mean rate of clearance of cerebrospinal fluid cryptococal infection (EFA). Non-inferiority was defined as an upper limit of the two-sided 95% confidence interval of difference in EFA between intervention and control less than 0.2 log10 colony forming units/ml/day.

The study was stopped at the pre-planned interim analysis as the primary objective had been achieved. All 3 study arms achieved the pre-defined 95% confidence level and the stringent 99% confidence level with no safety concerns for short course treatment.

Single dose L-AmB 10 mg/kg was well tolerated and led to non-inferior early fungicidal activity compared with 14 days of L-AmB 3 mg/kg in HIV-associated cryptococcal meningitis. This short course treatment strategy is now being tested against amphotericin B deoxycholate in a clinical end point trial.

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If confirmed to be effective, single high doses of L-AmB given with an optimized oral antifungal medication backbone would provide a feasible, well tolerated, and sustainable regimen for HIV-associated cryptococcal meningitis.

Gilead funded the trial through an Investigator award. Please refer to reference for a complete list of authors’ disclosures.


Jarvis JN, Leeme TB, Molefi M, et al. Short course high-dose liposomal amphotericin B for HIV-associated cryptococcal meningitis: A phase-II randomized controlled trial[published online June 26, 2018]. Clin Infect Dis. doi:10.1093/cid/ciy515/5045212