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Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis
Joseph N Jarvis1, David S Lawrence1, David B Meya1
1From the Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (J.N.J., D.S.L., N.Y.), the Institute for Infection and Immunity, St. George's University London (A.L., S.F.M., T.S.H.), and the Clinical Academic Group in Infection and Immunity, St. George's University Hospitals NHS Foundation Trust (T.S.H.), London, Liverpool School of Tropical Medicine (H.C.M., E.W., D.W., D.G.L., S. Jaffar) and the Department of Public Health, Policy, and Systems, Institute of Population Health (T.C.), and the Department of Pharmacology and Therapeutics, Institute of Systems, Molecular, and Integrative Biology (W.H.), University of Liverpool, Liverpool, and the Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter (T.S.H.) - all in the United Kingdom; the Botswana-Harvard AIDS Institute Partnership (J.N.J., D.S.L., M. Mosepele, T.L., K. Siamisang, N.Y.), the Departments of Internal Medicine (M. Mosepele) and Family Medicine and Public Health (K. Siamisang), University of Botswana, and the Department of Health Services Management, Ministry of Health and Wellness (K. Siamisang) - all in Gaborone, Botswana; the Infectious Diseases Institute, College of Health Sciences (D.B.M., E.K., J.K., E.M., M.K.R., K. Ssebambulidde, L.T., J.R., D.R.B., S. Jjunju, E.N.), and the Department of Medicine, School of Medicine (D.B.M.), Makerere University, Kampala, and Mbarara University of Science and Technology, Mbarara (C. Muzoora, E.N.) - both in Uganda; the University of Minnesota, Minneapolis (D.B.M., J.R., D.R.B.); the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (H.C.M., M. Moyo, H.M., D.G.L.) and the Department of Medicine, Kamuzu University of Health Sciences (H.C.M., M. Moyo), Blantyre, and the Lilongwe Medical Relief Fund Trust (University of North Carolina-Malawi Project), Lilongwe (C.K., M.C.H., C.C.) - all in Malawi; the Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill (M.C.H.); the Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine (G.M., C.S., K.C., A.S.), and the Department of Medicine (G.M., C.S., K.C.), University of Cape Town, and the Department of Radiology, Groote Schuur Hospital (A.S.) - both in Cape Town, South Africa; the Internal Medicine Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare (C.E.N., A.H., C. Mutata); Institut Pasteur, National Center for Scientific Research, Molecular Mycology Unit and National Reference Center for Invasive Mycoses and Antifungals, Unités Mixtes de Recherche 2000, and Université de Paris, Necker Pasteur Center for Infectious Diseases and Tropical Medicine, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Institut Hospitalo-Universitaire Imagine - both in Paris (T.B.-C., O.L.).
A new treatment using a single high dose of liposomal amphotericin B for cryptococcal meningitis in HIV-positive adults was found to be as effective as the standard treatment. This approach also resulted in fewer adverse events, offering a potentially improved therapeutic option.
Area of Science:
- Infectious Diseases
- Clinical Trials
- HIV/AIDS Research
Background:
- Cryptococcal meningitis is a significant cause of mortality in individuals with human immunodeficiency virus (HIV) in sub-Saharan Africa.
- The efficacy of a treatment regimen involving a single high dose of liposomal amphotericin B for cryptococcal meningitis remains undetermined.
Purpose of the Study:
- To evaluate the efficacy and safety of a single high dose of liposomal amphotericin B compared to the current World Health Organization (WHO)-recommended treatment for HIV-associated cryptococcal meningitis.
Main Methods:
- A phase 3, randomized, controlled, noninferiority trial was conducted across five African countries.
- HIV-positive adults with cryptococcal meningitis were randomized to receive either a single high dose of liposomal amphotericin B plus flucytosine and fluconazole, or the standard WHO-recommended treatment.
- The primary endpoint was all-cause mortality at 10 weeks, with the trial powered to demonstrate noninferiority within a 10-percentage-point margin.
Main Results:
- A total of 844 participants were randomized, with 814 included in the intention-to-treat analysis.
- At 10 weeks, 24.8% of participants in the liposomal amphotericin B group died, compared to 28.7% in the control group, demonstrating noninferiority (P<0.001).
- The liposomal amphotericin B group experienced fewer grade 3 or 4 adverse events (50.0% vs. 62.3%) compared to the control group.
Conclusions:
- A single high dose of liposomal amphotericin B, in combination with flucytosine and fluconazole, is noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis.
- This novel regimen was associated with a reduced incidence of severe adverse events, suggesting a potentially safer treatment option.
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