ACTG‐A5164, 2009.

Study characteristics
Methods	RCT
Participants	282 people with AIDS‐related OIs (TB excluded), 85% male 78 African‐American; 91 Hispanic; 18 from South Africa 10 with HIV + PDH 241 ART‐naive at study entry
Interventions	Early ART (< 14 days, median 12 days) Deferred ART (≥ 28 days, median 45 days) after start of OI treatment
Outcomes	Primary: composite: 3 ordered categories: death/AIDS progression no progression HIV VL ≥ 50 copies/mL no progression HIV VL < 50 copies/mL For ALL participants there was no statistically significant difference in the composite outcome between early and deferred ART groups. Secondary: AIDS progression/death; CD4 count at 24/48 weeks; HIV VL < 50% at 48 weeks, safety parameters including IRIS. Death/AIDS progression in ALL participants Favours early treatment Deaths in people with histoplasmosis in early ART group: 1/7 Deaths in people with histoplasmosis in deferred ART group: 0/3 Safety: IRIS; lab adverse events Grades 2–4; clinical adverse events Grades 2–4
Age	Median 38 years
Setting	USA including Puerto Rico, ZAF
Disease severity	Median CD4+ T cell count 29 cells/µL
Notes	NCT00055120, ACTG A5164
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random sequence generated by central computer using permuted blocks within Strata. Neither block size nor treatment assignments to other sites were public.
Allocation concealment (selection bias)	Unclear risk	No details provided in protocol or included study.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Protocol stated that for arm B (deferred ART), no study‐provided drugs were to be provided initially, hence blinding of participants and personnel was not possible.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Primary outcome was a composite endpoint of survival and VL. Detection bias was unlikely.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Equal numbers withdrew without primary endpoint data in each study arm. Details provided.
Selective reporting (reporting bias)	Low risk	Reported outcomes were consistent with protocol.