Achan 2012.

Methods	Open label, single site, randomized clinical trial
Participants	Participants were HIV infected children aged 2 months to 5 years eligible for ART or currently receiving NNRTI‐ based  ART with virological suppression (HIV RNA <400 copies/mL).
Interventions	Participants were randomized to receive either LPV/r‐based or NNRTI‐based ART and followed for 2 years. Control: NVP or EFV‐based regimen Intervention: LPV/r‐based regimen
Outcomes	Primary endpoint: Incidence‐density of malaria, defined as the number of incident episodes of malaria per time at risk. Secondary endpoints: ‐ Incidence of any adverse events, defined as severity grade 2 or higher that were possibly, probably or definitely related to study drugs ‐ Virologic efficacy of LPV/r versus NNRTI‐based ART in HIV‐infected children, with test for non‐inferiority in the proportion of children who achieve HIV viral RNA suppression at 48 weeks ‐ Immunologic efficacy of LPV/r versus NNRTI‐based ART, with test for non‐inferiority in the change from baseline CD4 cell count and % at 2 time points; 48 and 96 weeks. ‐ Association between nutritional status and HIV‐related outcomes, including ART levels.
Notes	Virologic and immunologic efficacy were predefined sub‐analyses but the trial was not design to compare the two ART regimens in terms of HIV disease outcomes.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Children were stratified by HIV treatment status (naive vs. on ART) to ensure balance between the intervention and control arms within these groups. To protect against temporal changes in either subject referral or study procedures, randomization will was blocked with a randomly permuted block size of 2 or 4 (from study protocol)
Allocation concealment (selection bias)	Low risk	Two sets of sealed sequentially numbered envelopes contained the treatment assignment and the assignment key was held in the central administrative data offices by a staff member not in contact with study subjects (from study protocol)
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	Unclear risk	2 children withdrew after randomisation/enrolment but before initiating study drug; 4 children prematurely stopped study arm drug (3 on NNRTI and 1 on PI). Noteworthy that 10 of the 12 premature withdrawals, including 3 of the 4 deaths, were from the NNRTI arm. While in no cases were withdrawals attributed to ART/NNRTI related reasons, this disproportionate loss from the NNRTI arm represents at least a potential for bias towards no significant differences in AE’s between the arms. ITT analysis.
Selective reporting (reporting bias)	Low risk	Study protocol available in the public domain, risk of selective reporting is very unlikely
Other bias	Unclear risk	The study was not designed or powered to compare treatment efficacy or to establish superiority of one of the two regimens.