Violari 2012.

Methods	Phase II randomised clinical trial
Participants	288 children less than 36 months old Age: > 2 months to < 36 months (up to but not including the 3rd birthday) Inclusion criteria: HIV‐1 RNA >5,000 copies/mL within 60 days prior to study entry/randomisation. This can also be considered as the confirmatory HIV test in patients in whom only one positive HIV test is available at the time of screening, at sites where only one HIV PCR is normally performed for diagnosis of HIV infection. ARV naïve except for ART used in attempts to prevent intrapartum MTCT. (Infant ART use for < 1 week postpartum for prevention of MTCT is allowed.) Treatment eligible as defined by the WHO paediatric algorithm. Parent or legal guardian able and willing to provide signed informed consent and to have the subject followed at the clinical site. Maternal use of ARVs during pregnancy and/or during labor is permitted with the exception of NNRTIs. Documentation of lack of NVP exposure. Exclusion criteria: Grade >2 AST or ALT at screening. Any Grade >3 laboratory toxicity at screening. Receipt of ART other than for prevention of intrapartum MTCT. Infants who received ART past the first week of life (e.g. for prevention of breast milk transmission) were excluded from study entry. Acute, serious infections requiring active treatment (prophylaxis allowed [e.g. PCP, cryptococcal meningitis]). Subjects could be receiving treatment for active TB if this did not include rifamycin drugs, and with approval by the study chairs. Chemotherapy for active malignancy. History of cardiac conduction abnormality and underlying structural heart disease.Report of any maternal NVP or other NNRTI exposure prior to or during the pregnancy and during breastfeeding with this child, including single dose NVP, documented by either verbal report or through the clinic or hospital record (use of ART from the NRTI or PI classes was allowed). Report of infant NVP exposure at any time, including during the first week of life, documented by either verbal report or through the clinic or hospital record.
Interventions	NVP‐based vs LPV/r‐based first line antiretroviral therapy
Outcomes	Treatment failure (virological failure or discontinuation for any cause included death) at 24 weeks; virological failure or death at 24 weeks; time to treatment failure (virological failure or discontinuation for any cause included death); time to virological failure or death; change in CD4%; change in weight and height z scores; adverse events
Notes	In October 2010, the Data Safety Monitoring Board recommended un‐blinding the study results.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from the protocol:"dynamic permuted block system [stratified (<12months>)] "
Allocation concealment (selection bias)	Low risk	Quote from correspondence: " The Subject Registration and Randomization System provides a web‐based interface that leads site personnel through the checklist. If the subject satisfies the entry criteria, the system stores the subject's information in the central database and assigns a treatment based on a permuted block algorithm"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	None (from correspondence), but outcome measurements are unlikely to be biased by unmasking
Blinding of outcome assessment (detection bias) All outcomes	Low risk	None (from correspondence), but outcome measurements are unlikely to be biased by unmasking
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT was performed and attrition bias is unlikely
Selective reporting (reporting bias)	Low risk	Protocol available, selective outcome reporting is unlikely
Other bias	Unclear risk	Early termination of the study:"In October 2010, the Data Safety Monitoring Board recommended un‐blinding the study results. "