Gray 2014.

Methods	Trial design: double‐blind, randomized placebo‐controlled trial. Follow‐up: full blood count, liver function tests, urea and electrolyte tests, percentage of CD4 cells and viral load were measured at baseline and 6‐monthly. CXR was performed at baseline, and additional CXRs were taken if clinically indicated. Adverse events: symptoms of adverse reactions to INH were recorded at each study visit.
Participants	Number of participants: 167 Median (IQR) age at baseline: 35 months (15 to 65) Inclusion criteria: age > 8 weeks, on ART for greater than 2 months, weight > 2.5 kg, adherence to ART of > 90%, prior history of TB treatment or prophylaxis, informed consent, resident in the area, access to transport. Exclusion criteria: chronic diarrhoea, currently using isoniazid prophylaxis, exposure to a TB contact, history of prior isoniazid hypersensitivity, severe anaemia (haemoglobin less than 7 gm/dL), neutropenia (absolute neutrophil count less than 400 cells/µL), thrombocytopenia (platelet count less than 50 000/µL), non‐reversible renal failure.
Interventions	Isoniazid, 10 mg/kg/dose with a variability of 8 mg/kg to 12 mg/kg, either three times weekly or daily for a median duration of 34 months. Placebo, had an identical appearance to isoniazid tablet, received either three times weekly or daily for a median duration of 34 months. All children were on ART and had adherence of at least 90% at baseline.
Outcomes	Active TB Death Adverse events Not included in this review Adherence to TB treatment Hospital admissions
Notes	Definitions: ‐ Definite TB: a microbiological or histological identification of Mycobacterium tuberculosis. ‐ Probable TB: based on a combination of typical clinical symptoms and signs, tuberculin skin testing, chest radiography, a history of close TB contact, and a documented response to antimycobacterial therapy. Country: South Africa Prevalence of isoniazid resistance: 0% Positive tuberculin test: 16% Funding: The study was funded by the Medical Research Council, South Africa; the National Research Foundation, Department of Health, South Africa; and the Discovery Foundation.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization list was created using permuted blocks, stratified by HIV infection status and balanced by study site.
Allocation concealment (selection bias)	Low risk	Treatment groups were centrally allocated.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Placebo had an identical appearance to INH tablets and was administered in a double blind matter".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"The chest radiographs were reported by a radiologist blinded to the prophylactic regimen to which the child was allocated. Diagnosis of TB was independently reviewed by an experienced clinician blinded to study randomisation".
Incomplete outcome data (attrition bias) All outcomes	Low risk	Intention‐to‐treat analysis was followed. All participants randomized were included in analysis.
Selective reporting (reporting bias)	Low risk	Outcomes stated in the protocol were included in the published manuscript.
Other bias	Low risk	None suspected.