Daily versus thrice-weekly antituberculosis therapy for drug-susceptible pulmonary tuberculosis in adults: A systematic review and exploratory meta-analysis.
DOI:
https://doi.org/10.51168/z25wzc51Keywords:
Tuberculosis, Pulmonary, Antitubercular Agents, Drug Therapy, Directly Observed Therapy, Treatment Outcome, Drug Resistance, Microbial, Sputum Conversion, Systematic Review, Meta-AnalysisAbstract
Background:
Historical thrice-weekly antituberculosis regimens reduced the number of supervised treatment encounters, but concerns remain regarding microbiological efficacy, relapse, and acquired resistance compared with daily therapy. This systematic review and exploratory meta-analysis aimed to compare the efficacy, safety, treatment outcomes, relapse, and acquired drug resistance associated with daily versus thrice-weekly antituberculosis therapy in adults with drug-susceptible pulmonary tuberculosis.
Methods:
Comparative randomized and observational studies involving adults with drug-susceptible or presumed drug-susceptible pulmonary tuberculosis were synthesized. Risk ratios (RRs) were calculated for dichotomous outcomes. Randomized evidence was prioritized, while pooled analyses incorporating observational studies were considered exploratory. Risk of bias was assessed using Cochrane RoB 2 for randomized trials and ROBINS-I for observational studies, and certainty of evidence was evaluated using GRADE principles.
Results:
Six unique studies constituted the strict/historical adult-focused evidence set, with two additional observational studies included as supportive sensitivity evidence. Two-month culture conversion was higher with daily than thrice-weekly treatment (85% vs 77%; RR 1.10, 95% CI 1.04–1.17). In the HIV-positive whole-course randomized trial, favourable outcome was 91% versus 77% (RR 1.19, 95% CI 1.05–1.35), with acquired rifampicin resistance occurring only in the intermittent arm. The exploratory pooled favourable-outcome estimate was RR 1.08 (95% CI 0.94–1.24; I²=22.6%). Safety evidence remained sparse and heterogeneous.
Conclusions:
Randomized evidence most consistently favours daily therapy for microbiological conversion and prevention of acquired resistance. Planned thrice-weekly therapy should not be preferred over guideline-concordant daily treatment. Future research should prioritize patient-centred delivery of daily therapy, predictors of toxicity and poor drug exposure, consequences of missed doses, and individual-patient-data analyses to identify clinically vulnerable subgroups.
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Copyright (c) 2026 Dr. Suvendu Kumar Panda, Dr. Snehasini Dash, Dr. Pratyush Mishra, Dr. Srikanta Panigrahy, Dr. Rashmi Ranjan Bhadra
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