Significant numbers of patients have been enrolled into clinical trials of treatment for human immunodeficiency virus (HIV)-associated cryptococcal meningitis over the past 3 decades, delivering a robust foundation of data on which to base treatment guidelines. However, mortality with optimized current treatment remains high—there is a pressing need to develop novel drugs.

The optimal induction therapy is a single high-dose of liposomal amphotericin B (10 mg/kg) plus flucytosine (100 mg/kg/day) and high-dose fluconazole (1200 mg/day) each for 14 days. This is followed by consolidation with fluconazole (800 mg/day) for 8 weeks and then long-term maintenance. However, the availability of both liposomal amphotericin B and flucytosine is limited in many high-burden settings, meaning alternative inferior regimens have to be used.

Alternative, currently available antifungals and attempts at drug repurposing have so far shown disappointing efficacy, but novel antifungal agents are in development and show promise.