Study:Pietrobon 2004.Outcome: relapse of histoplasmosis
Confounding domains	Measured variable(s)	Is there evidence that controlling for this variable was unnecessary?	Is the confounding domain measured validly and reliably?	OPTIONAL Is failure to adjust for this variable expected to favour intervention or comparator
Severity of PDH	Not defined or reported.	No	No	—
Severity of HIV	Authors reported 8/12 participants with histoplasmosis had CD4 count < 50 cells/μL	No	Yes	—
Comorbidities and comedications	Authors reported none of participants were receiving ART. Study population was 16. This included participants with various opportunistic infections. Coinfection with Cryptococcus neoformans reported in 1 participant; however, authors did not specify if this participant also had histoplasmosis.	No	No	—
Cointerventions	Is there evidence that controlling for this cointervention was unnecessary?		Is presence of this cointervention likely to favour outcomes in the intervention or comparator?
ART at time of PDH diagnosis	No		—
Supportive therapy	No		—
Bias domain	Signalling questions	Comments		Risk of bias judgement
Bias due to confounding	1.1–1.8	Follow‐up periods not reported. Duration of ITRA or FCN not reported. Switches between regimens not reported. Concurrent medication not reported. No statistical methods to control for confounding reported.		Critical
Bias in participant selection	2.1–2.5	Participants treated with maintenance therapy would have responded to initial treatment. Time to commencement of maintenance therapy not reported. Insufficient information to judge if start of follow‐up and start of intervention coincided for most participants.		No information
Bias in classification of intervention	3.1–3.3	Commencement of maintenance therapy was dependent on response to initial therapy with AmB. Intervention status was not well defined.		Serious
Bias due to deviations from intended intervention	4.1–4.6	No reported deviations from intended intervention.		No information
Bias due to missing data	5.1–5.5	Outcome data available for all participants.		Low
Bias in measurement of outcomes	6.1–6.4	Relapse was not clearly defined. Time periods were not reported. The outcome measure was subjective and assessed by assessors aware of the intervention.		Serious
Bias in selection of reported result	7.1–7.3	Descriptive retrospective study. No protocol; however, there was no indication of selection of the cohort for analysis and reporting on the basis of the result.		Moderate
Overall bias				Critical