Brouwer 2004.

Methods	Study type: Unblinded RCT Setting: 1 hospital in Thailand
Participants	Inclusion criteria: HIV infected; diagnosed by CSF India ink or CrAg test Exclusion criteria: pregnant; previous cryptococcal meningitis; ALT > 5 times upper limit of normal; ANC < 500 x 106/L; platelet count < 50 x 106/L; previous serious reaction to study drugs Number randomized: 64 Age: median 33 years Gender: 60% male CD4 T‐cell count: median 9 cells/μL Baseline ART: no Baseline GCS/AMS: GCS < 15 or seizures in 19% of participants
Interventions	Intervention AmBd 0.7 mg/kg/day for 2 weeks AmBd 0.7 mg/kg/day and flucytosine 100 mg/kg/day for 2 weeks AmBd 0.7 mg/kg/day and fluconazole 400 mg/day for 2 weeks AmBd 0.7 mg/kg/day and flucytosine 100 mg/kg/day and fluconazole 400 mg/day for 2 weeks Consolidation: fluconazole 400 mg/day for 8 weeks, then 200 mg/day maintenance dose Postdiagnosis ART: no participants started on ART within 10 weeks of follow‐up Lumbar puncture schedule: scheduled on days 3, 7, and 14 and as clinically indicated Laboratory monitoring: not specified
Outcomes	Primary outcome Rate of decrease in cryptococcal counts in CSF during first 2 weeks Secondary outcome Mortality at 2 and 10 weeks Outcome assessment schedule: daily while hospitalized and scheduled assessments on days 21, 28, 42, 80, and 182
Notes	Date of study: 2002 Funding: Wellcome Trust; Lancet international fellowship; St George’s Hospital; Netherlands Foundation for the Advancement of Tropical Medicine 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 with blocks of 16 with pre‐study generation of sealed envelopes prepared by an independent person
Allocation concealment (selection bias)	Low risk	Sealed envelopes prepared by independent person
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	Outcomes up to 10 weeks for all participants
Selective reporting (reporting bias)	Low risk	Authors reported all primary and secondary outcomes.
Other bias	Low risk	None noted.