Wamalwa 2012.

Methods	Open label randomised clinical trial.
Participants	150 infants who initiated HAART at <13 months of age Inclusion Criteria: A. Infants newly initiating HAART ‐ Less than 13 months of age ‐ HIV‐1 DNA detection with confirmation (positive on two HIV‐1 DNA filter paper tests) ‐ Caregiver of infant plans to reside in Nairobi for at least 3 years (reported by caregiver) ‐ Caregiver is able to provide sufficient location information B. Infants already receiving HAART ‐ Initiated HAART at <13 months of age ‐ Records confirming HIV positive status ‐ Documentation of CD4% and weight prior to HAART initiation ‐ Must be on 1st line drug regimen Eligibility for randomisation: ‐ Completed 24 months of treatment with HAART ‐ Normalized growth: weight for height z‐score > ‐0.5; Child's weight must be above the 5th weight‐for‐age percentile and the weight curve must not be flat or falling (i.e. cross 2 major percentile lines or more over the past 3 months) ‐ CD4% >= 25 ‐ Children who recently initiated or who require anti‐tuberculosis treatment at the time of randomisation were ineligible for randomisation.
Interventions	Infants will be treated with HAART regimen for 24 months after which those who have immune reconstitution and adequate growth (˜100) will be randomised to continuous versus deferred therapy. Clinical outcomes will be compared in these children to determine if interruption is a safe and beneficial strategy.
Outcomes	Primary outcome: growth and severe adverse events Secondary outcome: Incidence of morbidities, specifically pneumonia, diarrhoea, and hospitalisation. CD4% and VL post‐randomisation
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from the protocol: "Block randomization scheme with variable block sizes was generated using STATA 8.0 ralloc.ado v2.2.1.  Treatments were allocated in 1:1 ratio.  Blocks of variable sizes were generated in equal proportions.  All the study investigators and staff will be blinded to the block number, block size and sequence in the block."
Allocation concealment (selection bias)	Low risk	Quote from the protocol: "The treatments will be assigned via pre‐prepared sealed, opaque envelopes and the envelopes will be ordered in the sequence of treatment assignments generated by the STATA code."
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	None (by study design). Outcome measurements could be potentially biased by unmasking
Blinding of outcome assessment (detection bias) All outcomes	Low risk	(from correspondence) " Outcomes (virologic, immunologic) and adverse events (laboratory assays for signs of toxicity) were assessed by the lab without reference to treatment allocation.Growth measurements and morbidity assessments were performed in an unblinded fashion, standard protocols for measurement of growth parameters and for documentation of adverse events were employed for each arm. Analysis was blinded to arm allocation."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition was similar in each arm and was due to similar reasons (2 participants withdrew post‐randomization,1 in each arm). ITT analysis was performed by censoring LTFU.
Selective reporting (reporting bias)	Low risk	Protocol available, endpoints have been reported as pre‐specified and selective outcome reporting is unlikely
Other bias	High risk	The sample size calculation did not account for either early restart or unplanned interruption.  In addition, the sample size calculation was performed before the change in treatment guidelines to recommend initiation of ART for children with a CD4% less than 25% (increased from 20%).  This change in treatment guidelines prompted a revision in criteria for restart of ART in the interrupted arm from 20% to 25%. DSMB recommended early termination of the study due to high proportion of early restart.