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Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis

Jarvis, Joseph N., Lawrence, David S., Meya, David B., Kagimu, Enock, Kasibante, John, Mpoza, Edward, Rutakingirwa, Morris K., Ssebambulidde, Kenneth, Tugume, Lillian, Rhein, Joshua, Boulware, David R., Mwandumba, Henry ORCID:, Moyo, Melanie, Mzinganjira, Henry, Kanyama, Cecilia, Hosseinipour, Mina C., Chawinga, Chimwemwe, Meintjes, Graeme, Schutz, Charlotte, Comins, Kyla, Singh, Achita, Muzoora, Conrad, Jjunju, Samuel, Nuwagira, Edwin, Mosepele, Mosepele, Leeme, Tshepo, Siamisang, Keatlaretse, Ndhlovu, Chiratidzo E., Hlupeni, Admire, Mutata, Constantine, van Widenfelt, Erik, Chen, Tao, Wang, Duolao ORCID:, Hope, William, Boyer-Chammard, Timothée, Loyse, Angela, Molloy, Síle F., Youssouf, Nabila, Lortholary, Olivier, Lalloo, David ORCID:, Jaffar, Shabbar ORCID: and Harrison, Thomas S. (2022) 'Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis'. New England Journal of Medicine, Vol 386, Issue 12, pp. 1109-1120.

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Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)–related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known.


In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio 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 primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin.


A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, −3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was −0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and −0.42 log10 CFU per milliliter per day in the control group. 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%).


Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events.

Item Type: Article
Additional Information: *
Subjects: QV Pharmacology > Anti-Bacterial Agents. Tissue Extracts > QV 350 Anti-bacterial agents (General or not elsewhere classified)
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 245 Meningococcal infections
WL Nervous System > WL 200 Meninges. Blood-brain barrier
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI):
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 26 May 2022 12:57
Last Modified: 20 Jun 2023 13:16


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