Effects of missed anti-tuberculosis therapy doses on treatment outcome: a multi-center cohort studyResearch in context

Summary: 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. Theref...

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Main Authors: Isabella B.B. Ferreira, Rodrigo C. Menezes, Mariana Araújo-Pereira, Valeria C. Rolla, Afrânio L. Kritski, Marcelo Cordeiro-Santos, Timothy R. Sterling, Cody Staats, Gustavo Amorim, Anete Trajman, Bruno B. Andrade, A. Benjamin, Q. Medeiros, F. Ridolfi, A. Gomes-Silva, J. Oliveira, J. Marine, B. Durovni, S. Cavalcante, A. Rezende, A. Bezerra, A. Carvalho, A. Brito, A. Costa, R. Spener-Gomes, M. Rocha, V. Nascimento, B. Nogueira, A. Andrade, E. Silva
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:The Lancet Regional Health. Americas
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667193X25001723
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author Isabella B.B. Ferreira
Rodrigo C. Menezes
Mariana Araújo-Pereira
Valeria C. Rolla
Afrânio L. Kritski
Marcelo Cordeiro-Santos
Timothy R. Sterling
Cody Staats
Gustavo Amorim
Anete Trajman
Bruno B. Andrade
A. Benjamin
Q. Medeiros
F. Ridolfi
A. Gomes-Silva
J. Oliveira
J. Marine
B. Durovni
S. Cavalcante
A. Rezende
A. Bezerra
A. Carvalho
A. Brito
A. Costa
R. Spener-Gomes
M. Rocha
V. Nascimento
B. Nogueira
A. Andrade
E. Silva
author_facet Isabella B.B. Ferreira
Rodrigo C. Menezes
Mariana Araújo-Pereira
Valeria C. Rolla
Afrânio L. Kritski
Marcelo Cordeiro-Santos
Timothy R. Sterling
Cody Staats
Gustavo Amorim
Anete Trajman
Bruno B. Andrade
A. Benjamin
Q. Medeiros
F. Ridolfi
A. Gomes-Silva
J. Oliveira
J. Marine
B. Durovni
S. Cavalcante
A. Rezende
A. Bezerra
A. Carvalho
A. Brito
A. Costa
R. Spener-Gomes
M. Rocha
V. Nascimento
B. Nogueira
A. Andrade
E. Silva
author_sort Isabella B.B. Ferreira
collection DOAJ
description Summary: 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 study that followed adults with drug-sensitive TB for two years after TB treatment initiation at five clinical centers of the RePORT-Brazil cohort between June 2015 and June 2019. Participants not in DOT or followed for less than 30 days were excluded. Nonadherence was defined as the percentage of missed doses relative to the prescribed regimen, monitored daily through DOT. The primary composite outcome comprised treatment failure, disease recurrence, drug resistance, death, or loss to follow-up (LTFU) after 30 days of treatment. Associations were assessed with multivariable logistic regression. Findings: Among the 578 participants analyzed, 218 (37·7%) experienced unfavorable outcomes. Overall, 23% of participants missed more than 10% of prescribed doses, and this group had an 81·2% likelihood of experiencing unfavorable outcomes, compared to only 21·6% among those with complete adherence. A significant association was observed between the percentage of missed doses and unfavorable outcomes (adjusted OR: 1·11, 95% CI: 1·07–1·14, p-value < 0·0001). Interpretation: Even minor nonadherence in TB treatment was associated with an increased risk of unfavorable outcomes, highlighting the role of adherence in successful TB care. Funding: Fundação Oswaldo Cruz, Fundação José Silveira, Departamento de Ciência e Tecnologia, US National Institute of Allergy and Infectious Diseases.
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spelling doaj-art-c4d64dba801e4a21983f0932ff2ab1782025-08-20T03:26:56ZengElsevierThe Lancet Regional Health. Americas2667-193X2025-08-014810116210.1016/j.lana.2025.101162Effects of missed anti-tuberculosis therapy doses on treatment outcome: a multi-center cohort studyResearch in contextIsabella B.B. Ferreira0Rodrigo C. Menezes1Mariana Araújo-Pereira2Valeria C. Rolla3Afrânio L. Kritski4Marcelo Cordeiro-Santos5Timothy R. Sterling6Cody Staats7Gustavo Amorim8Anete Trajman9Bruno B. Andrade10A. BenjaminQ. MedeirosF. RidolfiA. Gomes-SilvaJ. OliveiraJ. MarineB. DurovniS. CavalcanteA. RezendeA. BezerraA. CarvalhoA. BritoA. CostaR. Spener-GomesM. RochaV. NascimentoB. NogueiraA. AndradeE. SilvaEscola Bahiana de Medicina e Saúde Pública, Pós-graduação em Medicina e Saúde Humana, Salvador, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Institute, Salvador, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Institute, Salvador, Brazil; Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Muniz, Fundação Oswaldo Cruz, Salvador, Brazil; Curso de Medicina, Faculdade ZARNS, Clariens Educação, Salvador, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Institute, Salvador, Brazil; Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Muniz, Fundação Oswaldo Cruz, Salvador, Brazil; Curso de Medicina, Faculdade ZARNS, Clariens Educação, Salvador, BrazilLaboratório de Pesquisa Clínica em Micobacterioses, Instituto Nacional de Infectologia Evandro Chagas/FIOCRUZ, Rio de Janeiro, BrazilUniversidade Federal do Rio de Janeiro, Programa Acadêmico de Tuberculose, Rio de Janeiro, BrazilGrupo de Pesquisa em Tuberculose, Fundação Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil; Curso de Medicina, Universidade do Estado do Amazonas (UEA), Manaus, BrazilDivision of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USADivision of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, USADepartamento de Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilEscola Bahiana de Medicina e Saúde Pública, Pós-graduação em Medicina e Saúde Humana, Salvador, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Institute, Salvador, Brazil; Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Muniz, Fundação Oswaldo Cruz, Salvador, Brazil; Curso de Medicina, Faculdade ZARNS, Clariens Educação, Salvador, Brazil; Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Corresponding author. Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, 40296-710, Brazil.Summary: 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 study that followed adults with drug-sensitive TB for two years after TB treatment initiation at five clinical centers of the RePORT-Brazil cohort between June 2015 and June 2019. Participants not in DOT or followed for less than 30 days were excluded. Nonadherence was defined as the percentage of missed doses relative to the prescribed regimen, monitored daily through DOT. The primary composite outcome comprised treatment failure, disease recurrence, drug resistance, death, or loss to follow-up (LTFU) after 30 days of treatment. Associations were assessed with multivariable logistic regression. Findings: Among the 578 participants analyzed, 218 (37·7%) experienced unfavorable outcomes. Overall, 23% of participants missed more than 10% of prescribed doses, and this group had an 81·2% likelihood of experiencing unfavorable outcomes, compared to only 21·6% among those with complete adherence. A significant association was observed between the percentage of missed doses and unfavorable outcomes (adjusted OR: 1·11, 95% CI: 1·07–1·14, p-value < 0·0001). Interpretation: Even minor nonadherence in TB treatment was associated with an increased risk of unfavorable outcomes, highlighting the role of adherence in successful TB care. Funding: Fundação Oswaldo Cruz, Fundação José Silveira, Departamento de Ciência e Tecnologia, US National Institute of Allergy and Infectious Diseases.http://www.sciencedirect.com/science/article/pii/S2667193X25001723TuberculosisAdherenceTreatmentComplianceUnfavorable treatment outcome
spellingShingle Isabella B.B. Ferreira
Rodrigo C. Menezes
Mariana Araújo-Pereira
Valeria C. Rolla
Afrânio L. Kritski
Marcelo Cordeiro-Santos
Timothy R. Sterling
Cody Staats
Gustavo Amorim
Anete Trajman
Bruno B. Andrade
A. Benjamin
Q. Medeiros
F. Ridolfi
A. Gomes-Silva
J. Oliveira
J. Marine
B. Durovni
S. Cavalcante
A. Rezende
A. Bezerra
A. Carvalho
A. Brito
A. Costa
R. Spener-Gomes
M. Rocha
V. Nascimento
B. Nogueira
A. Andrade
E. Silva
Effects of missed anti-tuberculosis therapy doses on treatment outcome: a multi-center cohort studyResearch in context
The Lancet Regional Health. Americas
Tuberculosis
Adherence
Treatment
Compliance
Unfavorable treatment outcome
title Effects of missed anti-tuberculosis therapy doses on treatment outcome: a multi-center cohort studyResearch in context
title_full Effects of missed anti-tuberculosis therapy doses on treatment outcome: a multi-center cohort studyResearch in context
title_fullStr Effects of missed anti-tuberculosis therapy doses on treatment outcome: a multi-center cohort studyResearch in context
title_full_unstemmed Effects of missed anti-tuberculosis therapy doses on treatment outcome: a multi-center cohort studyResearch in context
title_short Effects of missed anti-tuberculosis therapy doses on treatment outcome: a multi-center cohort studyResearch in context
title_sort effects of missed anti tuberculosis therapy doses on treatment outcome a multi center cohort studyresearch in context
topic Tuberculosis
Adherence
Treatment
Compliance
Unfavorable treatment outcome
url http://www.sciencedirect.com/science/article/pii/S2667193X25001723
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