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Effects of Missed Anti-Tuberculosis Therapy Doses on Treatment Outcome: A Multi-Center Cohort Study
23 Pages Posted: 8 Jan 2025
More...Abstract
Background: Tuberculosis (TB) remains a leading cause of infectious disease mortality globally. Although directly observed therapy (DOT) has been widely implemented to improve adherence, nonadherence continues to compromise treatment success rates, especially in real-world settings. Therefore, this study aims to assess the impact of missed doses on TB treatment outcomes.
Methods: prospective observational cohort that followed participants for two years after TB treatment initiation at five clinical centers in Salvador, Rio de Janeiro, and Manaus, as part of the RePORT-Brazil cohort. Adult participants with drug-sensitive TB undergoing DOT between June 2015 and June 2019 were included. Participants were excluded if not enrolled in DOT or if follow-up was less than 30 days. Nonadherence was defined as the percentage of missed doses relative to the prescribed regimen, monitored daily through DOT and recorded monthly. The primary outcome was a composite of treatment failure, disease relapse, drug resistance, death, or loss to follow-up after 30 days of treatment. The secondary outcome excluded loss to follow-up to focus on clinical and bacteriological failure directly associated with missed doses.
Findings: Among the 578 participants analyzed, 23% missed more than 10% of prescribed doses. Participants missing 10% or more had an 81·2% likelihood of unfavorable outcomes, while those with complete adherence exhibited only a 21·6% probability of unfavorable outcomes. A significant association was observed between the percentage of missed doses and unfavorable outcomes (adjusted OR: 1·11 per 1% increase in missed doses, 95% CI: 1·07–1·14, p<0·001). Even minimal nonadherence, such as missing 2·8% of doses, led to a 10% increase in the predicted risk of unfavorable outcomes.
Interpretation: Even minor nonadherence in TB treatment was associated with an increased risk of unfavorable outcomes, highlighting the critical role of adherence in successful TB care. Targeted interventions to support adherence are essential to improve TB outcomes.
Funding: Fundação Oswaldo Cruz, Fundação José Silveira, Departamento de Ciência e Tecnologia, US National Institute of Allergy and Infectious Diseases.
Declaration of Interest: We declare no competing interests.
Ethical Approval: The study was conducted according to the principles in the Declaration of Helsinki. The RePORT-Brazil protocol was approved by the institutional review boards at each study site and at Vanderbilt University Medical Center. Participation in RePORT-Brazil was voluntary, and written informed consent was obtained from all participants.
Keywords: Tuberculosis, Adherence, Treatment, Compliance, Unfavorable Treatment Outcome
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