Jarvis 2012.

Methods	Study type: unblinded RCT Setting: 1 hospital in South Africa
Participants	Inclusion criteria: HIV infected; ART‐naive; ≥ 21 years of age; positive CSF India ink or CrAg test 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: 90 (2 excluded after randomization due to prior episode of cryptococcal meningitis and low platelets) Age: median 32 years Gender: 44% male CD4 T‐cell count: median 27 cells/μL Baseline ART: none (excluded if prior ART) Baseline GCS/AMS: GCS < 15 in 37% of participants
Interventions	Intervention AmBd 1.0 mg/kg/day and flucytosine 100 mg/kg/day for 2 weeks AmBd 1.0 mg/kg/day and flucytosine 100 mg/kg/day for 2 weeks with interferon gamma 100 μg days 1 and 3 AmBd 1.0 mg/kg/day and flucytosine 100 mg/kg/day for 2 weeks with interferon gamma 100 μg days 1, 3, 5, 8, 10, and 12 Consolidation: fluconazole 400 mg/day up to 8 weeks, then 200 mg/day maintenance dose Postdiagnosis ART: protocol for ART initiation between 2 and 4 weeks Lumbar puncture schedule: scheduled days 1, 3, 7, and 14 and as clinically indicated Laboratory monitoring: alternate‐day renal function and electrolyte testing and twice‐weekly CBC and LFTs during first 2 weeks
Outcomes	Primary outcome Rate of CSF fungal clearance in the first 2 weeks Secondary outcomes (Mortality at 2 and 10 weeks Serious adverse events Laboratory toxicities Outcome assessment schedule: daily while hospitalized, then up to 1 year after enrolment
Notes	Date of study: 2007 to 2010 Funding: Wellcome Trust 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 randomization with random computer‐generated lists with block sizes of 8, stratified by GCS of 15 or GCS < 15
Allocation concealment (selection bias)	Low risk	Numbers maintained in sealed envelopes prepared by independent individuals.
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 complete in all groups
Selective reporting (reporting bias)	Low risk	Authors reported on all primary and secondary outcomes.
Other bias	Low risk	None noted.