Conclusion
CM
This study demonstrates that weight-based and eGFR adjusted doses of FCZ between 1600mg/day and 2000mg/day are safe, well tolerated and effective in the induction phase of CM treatment and had similar times to achieve CSF sterilization, but took longer than AMB. Survival at these doses of FCZ were not statistically different than AMB. The WHO recommended dose of 1200mg FCZ in the induction phase was associated with poorer survival. The 2000mg FCZ was associated with more gastrointestinal side effects and offered no survival benefit over the 1600mg FCZ dose. A phase III study powered to show non-inferiority of higher doses FCZ to AMB is proposed. We recommend 1600mg FCZ in settings where AMB is not available, based on the current data. Future studies should investigate the addition of flucytosine to the higher FCZ doses and the efficacy of the newer, less toxic antifungal agents. Ultimately prevention and control of HIV which will reduce or eradicate the scourge of CM should be the universal goal.