Shorter Antitubercular Regimens Versus 9 Months of Isoniazid for Latent Tuberculosis in Children: A Systematic Review and Meta-Analysis

Background We conducted a systematic review and meta-analysis to compare effectiveness and safety of 9 months of isoniazid (9H) versus shorter rifamycin-containing regimens for treating latent tuberculosis infection (TBI) in children. Methods We systematically searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials to June 2025 for randomized, controlled trials (RCTs) and cohort studies that compared regimens that were shorter than 9 months of isoniazid in children aged 1-18 years. Outcomes were development of TB disease, treatment completion, and adverse events. Risk of bias was assessed using RoB 2.0 and the Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool; certainty of evidence was graded using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results Five RCTs and 7 nonrandomized studies that enrolled approximately 2950 children in trials and >25 000 in observational cohorts were included. In pooled analysis of 3 RCTs, shorter rifamycin-containing regimens resulted in little to no difference in development of TB disease compared with 9H (odds ratio [OR], 0.19; 95% confidence interval [CI], .03-1.12; moderate-certainty evidence). Treatment completion was probably higher with shorter regimens (OR, 0.51; 95% CI, .42-0.62; moderate-certainty evidence). Adverse events were similar between groups, but evidence is uncertain (low-certainty evidence). Observational data were consistent with these findings, showing higher completion rates and lower hepatotoxicity with shorter treatments. Conclusions Shorter rifamycin-containing regimens for pediatric TBI probably increase treatment completion and have similar safety outcomes, with no important difference in development of TB disease compared with the standard regimen. These findings support current guideline recommendations that favor shorter regimens in children.