Comparison of Early Fungicidal Activity and Mortality Between Daily Liposomal Amphotericin B and Daily Amphotericin B Deoxycholate for Cryptococcal Meningitis

Abstract

Abstract Background 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 noninferiority 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 B among persons with human immunodeficiency virus (HIV)–related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day. Methods We analyzed data from 3 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, cerebrospinal fluid (CSF) early fungicidal activity (EFA), and 10-week mortality. Results We included 498 participants in this analysis, of whom 201 had available EFA data (n = 46 liposomal amphotericin B; n = 155 amphotericin B deoxycholate). Overall, there is no statistical evidence that the antifungal activity of liposomal amphotericin B (mean EFA, 0.495 [95% confidence interval {CI}, .355–.634] log10 colony-forming units [CFU]/mL/day) differ from amphotericin B deoxycholate (mean EFA, 0.402 [95% CI, .360–.445] log10 CFU/mL) (P = .13). Mortality at 10 weeks trended lower for liposomal amphotericin B (28.2%) versus amphotericin B deoxycholate (34.6%) but was not statistically different when adjusting for baseline characteristics (adjusted hazard ratio, 0.74 [95% CI, .44–1.25]; P = .26). Conclusions 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.