Study:ACTG084, 1992.Outcome: response to therapy (prevention of relapse)
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	Participants required to have been treated successfully for confirmed disseminated histoplasmosis within 6 weeks of enrolment.	No	Unsure	—
Severity of HIV	CD4	No	Yes	—
Comorbidities and comedications	Protocol stipulated parameters on comorbidities and comedications.	No	Probably	—
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. Zidovudine use reported.		—
Supportive therapy	—		—
Bias domain	Signalling questions	Comments		Risk of bias judgement
Bias due to confounding	1.1–1.8	Severity of HIV infection and ART use were not controlled for with appropriate statistical methods.		Serious
Bias in participant selection	2.1–2.5	Selection into the study may have been related to the intervention and outcome. Start of follow‐up and start of intervention coincided for all participants.		Moderate
Bias in classification of intervention	3.1–3.3	Intervention status was clearly defined.		Low
Bias due to deviations from intended intervention	4.1–4.6	No reported deviations from usual practice. Management of HIV not reported.		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 determined by clinical assessment, Histoplasma c. antigen levels in urine and serum and blood cultures at predetermined intervals.		Low
Bias in selection of reported result	7.1–7.3	Reported results are consistent with preregistered protocol.		Low
Overall bias				Serious