Treating cryptococcal meningitis with liposomal amphotericin B
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by An Duc Thien Le |
Posted on April 26th, 2023
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Due to their immunodeficiency, HIV infected patients are more susceptible to opportunistic infections. Cryptococcal meningitis is the second leading cause of HIV-related death. The high mortality is due to either the ineffectiveness of the fluconazole or the high intoxicity of the long-course amphotericin B deoxycholate. Liposomal amphotericin B can be given at a higher dose due to its lower rate of side effects. Compounded with its ability to penetrate the blood-brain barrier and long half-life, a study had been conducted to examine the usage of Liposomal amphotericin B antifungal combination therapy in treating cryptococcal meningitis.
The phase 3 clinical trial was conducted in Botswana, Malawi, South Africa, Uganda, and Zimbabwe. The study included 844 adults who were HIV-positive with an average CD4 T-cell count of 27 cells per mm3 of blood. These patients were diagnosed with their first episode of cryptococcal meningitis with either microscopic identification or an antigen test. Approximately 95% of them are experiencing headache with an episode lasting around 2 weeks. Around 10% of the patients had experienced an episode of seizure within 72 before the study started. The patients were randomly assigned to receive either the current WHO recommended treatment plan or the liposomal amphotericin B based regimen. The WHO recommended standard of care included intravenous infusion 1 mg amphotericin B deoxycholate per kilogram per day for 7 days plus 100 mg of oral flucytosine per kilogram per day for 7 days; the combination was followed by 1 week of 1200 mg oral fluconazole per day. The new regimen included one single 10 mg dose of intravenous 10 mg liposomal amphotericin B infused on the first day and 2 weeks of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day). After 10 weeks of treatment, the mortality rate and fungal clearance rate were similar between the WHO recommended treatment plan and the liposomal amphotericin B regimen. Accounting for the fact that the novel therapy is more cost effective and liposomal amphotericin B caused 12% less side effect than the current regimen, it should be considered for mass usage.
The phase 3 clinical trial was conducted in Botswana, Malawi, South Africa, Uganda, and Zimbabwe. The study included 844 adults who were HIV-positive with an average CD4 T-cell count of 27 cells per mm3 of blood. These patients were diagnosed with their first episode of cryptococcal meningitis with either microscopic identification or an antigen test. Approximately 95% of them are experiencing headache with an episode lasting around 2 weeks. Around 10% of the patients had experienced an episode of seizure within 72 before the study started. The patients were randomly assigned to receive either the current WHO recommended treatment plan or the liposomal amphotericin B based regimen. The WHO recommended standard of care included intravenous infusion 1 mg amphotericin B deoxycholate per kilogram per day for 7 days plus 100 mg of oral flucytosine per kilogram per day for 7 days; the combination was followed by 1 week of 1200 mg oral fluconazole per day. The new regimen included one single 10 mg dose of intravenous 10 mg liposomal amphotericin B infused on the first day and 2 weeks of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day). After 10 weeks of treatment, the mortality rate and fungal clearance rate were similar between the WHO recommended treatment plan and the liposomal amphotericin B regimen. Accounting for the fact that the novel therapy is more cost effective and liposomal amphotericin B caused 12% less side effect than the current regimen, it should be considered for mass usage.