Loyse 2012.

Methods	Study type: unblinded RCT Setting: 2 hospitals in South Africa
Participants	Inclusion criteria: HIV infected; ART‐naive; ≥ 18 years of age; positive CSF India ink confirmed by culture Exclusion criteria: pregnant or breastfeeding; previous cryptococcal meningitis; ALT > 200 IU/mL; ANC < 500 x 106 cells/L; platelets < 50 x 106 cells/L; previous serious reaction to study drugs or contraindication to study drugs Number randomized: 80 (1 excluded after randomization for prior history of cryptococcal meningitis) Age: median 34 years Gender: 49% male CD4 T‐cell count: median 37 cells/μL Baseline ART: none (excluded if prior ART) Baseline GCS/AMS: GCS < 15 in 15% of participants
Interventions	Intervention AmBd 0.7 to 1.0 mg/kg/day and flucytosine 100 mg/kg/day for 2 weeks AmBd 0.7 to 1.0 mg/kg/day and fluconazole 800 mg/day for 2 weeks AmBd 0.7 to 1.0 mg/kg/day and fluconazole 1200 mg/day for 2 weeks AmBd 0.7 to 1.0 mg/kg/day and voriconazole 600 mg/day for 2 weeks Consolidation: fluconazole 400 mg/day up to 8 weeks, then 200 mg/day maintenance dose Postdiagnosis ART: protocol for ART initiation > 2 weeks after starting antifungal therapy Lumbar puncture schedule: scheduled days 3, 7, and 14 and as clinically indicated Laboratory monitoring: alternate‐day renal function, twice‐weekly CBC and LFTs
Outcomes	Primary outcome Rate of CSF fungal clearance in the first 2 weeks Secondary outcomes Mortality at 2 and 10 weeks Drug‐related clinical and laboratory adverse events Outcome assessment schedule: daily while hospitalized, started on ART at 2 weeks, and followed up to 6 months from enrolment
Notes	Date of study: 2006 to 2008 Funding: Wellcome Trust; Medical Research Council (UK) Declaration of conflict of interest by authors: none reported.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	1:1:1:1 randomization using computer‐generated sequence, stratified by baseline altered mental status
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	High risk	Treatment was not blinded.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcomes unblinded by assessors
Incomplete outcome data (attrition bias) All outcomes	Low risk	Vital status at 10 weeks in most (75/79) participants
Selective reporting (reporting bias)	Low risk	Authors reported on all primary and secondary outcomes.
Other bias	Low risk	None noted.