Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.



Jarvis, Joseph N ORCID: 0000-0003-1459-5554, Lawrence, David S, Meya, David B, Kagimu, Enock, Kasibante, John, Mpoza, Edward, Rutakingirwa, Morris K, Ssebambulidde, Kenneth ORCID: 0000-0002-8125-0698, Tugume, Lillian, Rhein, Joshua ORCID: 0000-0002-0480-9646
et al (show 33 more authors) (2022) Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. The New England journal of medicine, 386 (12). 1109 - 1120.

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Abstract

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 log<sub>10</sub> colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log<sub>10</sub> 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%).<h4>Conclusions</h4>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.).

Item Type: Article
Uncontrolled Keywords: Ambition Study Group, AIDS-Related Opportunistic Infections, Meningitis, Cryptococcal, HIV Infections, Amphotericin B, Fluconazole, Flucytosine, Antifungal Agents, Drug Therapy, Combination, Administration, Oral, Drug Administration Schedule, Africa South of the Sahara
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Population Health
Depositing User: Symplectic Admin
Date Deposited: 24 Mar 2022 08:56
Last Modified: 15 Sep 2022 01:12
DOI: 10.1056/nejmoa2111904
URI: https://livrepository.liverpool.ac.uk/id/eprint/3150874