Introduction
toxicity, deaths, death, CM
CRYPTOCOCCAL MENINGITIS, SECONDARY
An estimated 220 000 cases and 180 000 deaths occur annually from cryptococcal meningitis (CM), mostly in sub-Saharan Africa [An open label phase I/II dose-escalation (Stage-1) and dose-validation (Stage-2) study was planned to investigate the safety, tolerability, and efficacy of an induction-consolidation strategy of high-dose (1200mg-2000mg), daily oral FCZ alone for CM in PWH.The primary objectives were to determine the maximum tolerated dose (MTD) by comparing the safety and tolerability of induction FCZ regimens of 1200mg, 1600mg, and 2000mg/day combined with flucytosine where available. The secondary objectives were to compare the clinical outcomes, neurological status, and fungicidal effects of different induction regimens of FCZ during induction through 10 weeks and assess the time to death and the rates of dose limiting toxicity (DLT) and mortality. A concurrently randomized standard of care arm of AMB was included which was revised to allow AMB with flucytosine where available or FCZ per the revised WHO recommendations of December 2011.