ARROW trial team 2013.

Methods	Open‐label randomised trial
Participants	1206 symptomatic HIV infected infants and children in Uganda and Zimbabwe. Inclusion criteria: ART naive Children between 6 months to 17 years with confirmed, documented diagnosis of HIV‐1 infection and eligible for ART Parents or guardians, and children where appropriate according to age and knowledge of HIV status, must be willing and able to give informed consent for randomisation to clinically driven monitoring (CDM) or laboratory and clinical monitoring (LCM) and to first‐line ART strategy  Exclusion criteria Children who were:unlikely to attend regularly; likely to have poor adherence; with acute infection; receiving chemotherapy for malignancy or receiving medication contraindicated by ART; with laboratory abnormalities, which are a contraindication for the patient to start ART; pregnant or breastfeeding.
Interventions	Two strategic approaches for management of antiretroviral therapy (ART): 1. Clinically driven monitoring (CDM) or laboratory plus clinical monitoring (LCM). 2. Continuous first‐line ART with three drug, two class regimen, comprising two NRTIs plus one NNRTI, or induction with four drugs (two classes) followed by maintenance with three drugs.
Outcomes	The primary endpoints were:  1. Monitoring practice (n = 1206):  a. Efficacy: progression to a new WHO stage 4 event or death  b. Safety: any adverse events of grade 3 or 4, which are not HIV‐related only  2. ART strategies for first‐line therapy (n=1206):  a. Efficacy: Change in CD4 percentage at 72 and 144 weeks  b. Safety: any adverse events of grade 3 or 4, which are not HIV‐related only
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was stratified by centre, and by factorial randomisations within the overarching ARROW trial (CDM vs LCM, and first‐line ART induction/maintenance strategy). The computer‐generated sequentially numbered randomisation list (variable block sizes) was pre‐prepared by the Trial Statistician and incorporated within the secure database at each trial centre, connected to but not located within each clinical centre.
Allocation concealment (selection bias)	Low risk	Allocation was undertaken by clinicians phoning the local trials centre. Trial managers could access the next number but not the whole list.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	None, but outcomes are unlikely to be biased by unmasking
Blinding of outcome assessment (detection bias) All outcomes	Low risk	None, but outcome measurements are unlikely to be biased by unmasking
Incomplete outcome data (attrition bias) All outcomes	Low risk	"Of 1206 randomised, 28 withdrew or were lost to follow up during the whole follow up period (approximately 2.5% LTFU)" (from correspondence). ITT analysis.
Selective reporting (reporting bias)	Low risk	Study protocol available in the public domain, risk of selective reporting is very unlikely
Other bias	Low risk