Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis
Creators: name: Siamisang, Keatlaretse
name: Chen, Tao
name: Kagimu, Enock
name: Harrison, Thomas S
name: Lalloo, David G
name: Mwandumba, Henry C
name: Hosseinipour, Mina C
name: Youssouf, Nabila
name: Kasibante, John
name: Tugume, Lillian
name: Ssebambulidde, Kenneth
name: Comins, Kyla
name: Muzoora, Conrad
name: Meya, David B
name: Lawrence, David S
name: Meintjes, Graeme
name: Moyo, Melanie
name: Ndhlovu, Chiratidzo E
name: Wang, Duolao
name: Nuwagira, Edwin
name: Lortholary, Olivier
name: Boulware, David R
name: Boyer-Chammard, Timothee
name: Mutata, Constantine
name: Molloy, Si­le F
name: Rutakingirwa, Morris K
name: Hope, William
name: Mpoza, Edward
name: Schutz, Charlotte
name: Leeme, Tshepo
name: Jarvis, Joseph N
name: Ambition Study Group
name: Kanyama, Cecilia
name: Chawinga, Chimwemwe
name: van Widenfelt, Erik
name: Mzinganjira, Henry
name: Mosepele, Mosepele
name: Rhein, Joshua
name: Singh, Achita
name: Hlupeni, Admire
name: Jaffar, Shabbar
name: Jjunju, Samuel
name: Loyse, Angela
Publisher: name: Massachusetts Medical Society
Year: 2022

description: BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.).