Nussbaum 2010.

Methods	Study type: unblinded RCT Setting: 1 referral hospital in Malawi
Participants	Inclusion criteria: HIV infected; ART‐naive; diagnosed by CSF India ink or CrAg test Exclusion criteria: pregnant or breastfeeding; previous cryptococcal meningitis; ALT > 200 IU/mL; ANC < 500 x 106/L; platelets < 50 x 106/L; contraindication to any study medication Number randomized: 43 (3 excluded after randomization for breastfeeding, false diagnosis due to sampling error, and positive CSF CrAg but negative confirmatory culture) Age: median 36 years Gender: 66% male CD4 T‐cell count: median 21 cells/μL Baseline ART: none (excluded if prior ART) Baseline GCS/AMS: GCS < 15 in 39% of participants
Interventions	Intervention Fluconazole 1200 mg/day for 2 weeks Fluconazole 1200 mg/day and flucytosine 100 mg/kg/day for 2 weeks Consolidation: fluconazole 800 mg/day for 2 weeks, then 400 mg/day for 8 weeks, then 200 mg/day maintenance dose Postdiagnosis ART: ART initiated at 4 weeks. Lumbar puncture schedule: scheduled on days 1, 3, 7, and 14 and as clinically indicated Laboratory monitoring: at least 3 blood counts per week and AST, ALT, and chemistries once weekly for 2 weeks, with ALT and AST repeated at weeks 4, 6, and 10
Outcomes	Primary outcome Rate of CSF fungal clearance in first 2 weeks Secondary outcomes Mortality at 2 and 10 weeks Drug safety Serious adverse events Outcome assessment schedule: daily while hospitalized, then scheduled for visit at 4 weeks to initiate ART, then followed until 10 weeks
Notes	Date of study: 2008 (study terminated early when data safety monitoring committee found primary endpoint was reached in interim analysis) Funding: Medical Research Council (UK); UNC Center for AIDS Research 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 randomization stratified by GCS < 15 using random computer‐generated list with block size of 8
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 known for most participants (39/40) at 10 weeks
Selective reporting (reporting bias)	Low risk	Authors reported on all primary and secondary outcomes.
Other bias	Low risk	None noted.