Safety of Single High-Dose Liposomal Amphotericin B for Induction Treatment of Cryptococcal Meningitis and Histoplasmosis in People With HIV: A Systematic Review and Meta-analysis

BACKGROUND: Evidence for efficacy of single, high-dose liposomal amphotericin B (LAmB) in HIV-associated cryptococcal meningitis and histoplasmosis is growing. No systematic review has examined the safety of this regimen across multiple studies. METHODS: We systematically searched Medline, Scopus, and the Cochrane Library from inception to April 2023 for studies reporting grade 3 and 4 adverse events (AEs) with single high-dose LAmB vs traditional amphotericin regimens for HIV-associated fungal infections. RESULTS: Three trials (n = 946) were included. Compared with traditional regimens, single high-dose LAmB was associated with equivalent risk of grade 3 and 4 AEs (risk ratio [RR], 0.75; 95% CI, 0.53–1.06) and lower overall risk of grade 4 AEs (RR, 0.68; 95% CI, 0.55–0.86), grade 4 renal (RR, 0.43; 95% CI, 0.20–0.94) and grade 4 hematological AEs (RR, 0.46; 95% CI, 0.32–0.65). CONCLUSIONS: Single, high-dose LAmB is associated with a lower risk of life-threatening AEs compared with other World Health Organization–endorsed amphotericin B–based regimens in invasive HIV–related fungal infection.