%0 Journal Article
%T Comparison of early fungicidal activity and mortality between daily liposomal amphotericin B and daily amphotericin B deoxycholate among patients with HIV-associated cryptococcal meningitis.
%A Kimuda S
%A Kwizera R
%A Dai B
%A Kigozi E
%A Kasozi D
%A Rutakingirwa MK
%A Tukundane A
%A Shifah N
%A Luggya T
%A Luswata A
%A Ndyetukira JF
%A Yueh S
%A Mulwana S
%A Wele A
%A Bahr NC
%A Meya DB
%A Boulware DR
%A Skipper CP
%J Clin Infect Dis
%V 0
%N 0
%D 2024 Jun 29
%M 38943665
%F 20.999
%R 10.1093/cid/ciae326
%X <B>BACKGROUND: </B>Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet non-inferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin among persons with HIV-related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day.<BR><B>METHODS: </B>We analyzed data from three clinical studies involving participants with HIV-associated cryptococcal meningitis receiving either daily liposomal amphotericin B at 3 mg/kg/day with flucytosine (N = 94) or amphotericin B deoxycholate at 0.7-1.0 mg/kg/day with flucytosine (N = 404) as induction therapy. We compared participant baseline characteristics, CSF early fungicidal activity (EFA), and 10-week mortality.<BR><B>RESULTS: </B>We included 498 participants in this analysis, of whom 201 had available EFA data (N = 46 liposomal amphotericin; N = 155 amphotericin deoxycholate). Overall, there is no statistical evidence that the antifungal activity of liposomal amphotericin B (mean EFA = 0.495 log10 CFU/mL/day; 95%CI, 0.355-0.634) differ from amphotericin B deoxycholate (mean EFA = 0.402 log10 CFU/mL; 95%CI, 0.360-0.445) (P = 0.13). Mortality at 10 weeks trended lower for liposomal amphotericin (28.2%) vs amphotericin B deoxycholate (34.6%) but was not statistically different when adjusting for baseline characteristics (adjusted Hazard Ratio = 0.74; 95%CI, 0.44-1.25; P = 0.26).<BR><B>CONCLUSIONS: </B>Daily liposomal amphotericin B induction demonstrated a similar rate of CSF fungal clearance and 10-week mortality as amphotericin B deoxycholate when combined with flucytosine for the treatment of HIV-associated cryptococcal meningitis.