Violari 2008.

Methods	Phase 3 open‐label randomised control trial
Participants	377 infants 6 to 12 weeks of age who had HIV infection (DNA PCR positive; RNA above 1000 copies/ml) Inclusion criteria: CD4 percentage of 25% or more. Exclusion criteria: Presence of a severe CDC Stage B or Stage C disease, Grade 3 or 4 laboratory values for alanine aminotransferase (ALT) and aspartate aminotransferase (AST), absolute neutrophil count, haemoglobin, electrolytes, creatinine or clinical toxicity at screening, as defined by age appropriate toxicity tables; presence of any major congenital abnormalities that were life‐threatening and any acute and clinically significant medical event at randomisation; inability to tolerate oral medication; birth weight <2 kilograms; use of investigational drugs or any medications that are disallowed with protease inhibitors or non‐nucleoside reverse transcriptase inhibitors and; inability of parent or legal guardian to attend regularly scheduled study visits.
Interventions	Infants were randomly assigned to receive one of three treatments: early limited antiretroviral therapy for 96 weeks, early limited antiretroviral therapy for 40 weeks, or deferred therapy
Outcomes	By week 24: Time to death or failure of the first‐line antiretroviral therapy; HIV disease progression; change in CD4% during follow up; grade 3 and 4 drug‐related events.
Notes	After review by the data and safety monitoring board, the deferred‐therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomisation schedule was prepared centrally by the trial statistician and faxed to the study sites."
Allocation concealment (selection bias)	Low risk	Quote from correspondence: " prepared by the trial statistician and communicated by fax to the sites"
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	Quote: "An independent endpoint review committee reviewed all deaths and CDC stage C and severe stage B events without knowledge of CD4 values, status of antiretroviral therapy, or randomised treatment assignments.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Loss to follow up was 6% in the early treatment arm and 3% in deferred treatment arm. Intent to treat TT analysis was performed by censoring LTFU.
Selective reporting (reporting bias)	Low risk	Protocol available, selective outcome reporting is unlikely.
Other bias	Low risk	Early stop: "After a review by the data and safety monitoring board, the deferred‐therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy". The guiding statistical criterion for “proof beyond reasonable doubt” was based on a difference of at least 3 SD in the log relative hazard (or nominal P<0.001) in any interim analysis (according to the Haybittle–Peto rule).