Impact of adverse drug reactions on the outcomes of tuberculosis treatment

Flávia M Sant Anna; Mariana Araújo-Pereira; Carolina A S Schmaltz; María B Arriaga; Bruno B Andrade; Valeria C Rolla

doi:10.1371/journal.pone.0269765

Impact of adverse drug reactions on the outcomes of tuberculosis treatment

PLoS One. 2023 Feb 7;18(2):e0269765. doi: 10.1371/journal.pone.0269765. eCollection 2023.

Authors

Flávia M Sant Anna^{1

2}, Mariana Araújo-Pereira^{3

4

5}, Carolina A S Schmaltz², María B Arriaga^{3

4

5}, Bruno B Andrade^{3

4

5

6

7}, Valeria C Rolla^{1

2}

Affiliations

¹ Postgraduate Program Clinical Research in Infectious Diseases, National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
² Clinical Research Laboratory on Mycobacteria, (LAPCLIN-TB), National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
³ School of Medicine, Federal University of Bahia, Salvador, Brazil.
⁴ Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil.
⁵ Laboratory of Inflammation and Biomarkers, Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.
⁶ Curso de Medicina, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil.
⁷ Curso de Medicina, Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil.

Abstract

Background: Adverse drug reactions (ADR) challenge successful anti-tuberculosis treatment (ATT). The aim of this study was to evaluate the impact of ATT-associated ADR and related factors on ATT outcomes.

Methods: A prospective cohort study of persons with tuberculosis (TB) at a referral center in Rio de Janeiro, Brazil, from 2010 to 2016. Baseline information: race, sex, schooling, economic status, tobacco, drugs and alcohol abuse, HIV-infection status and comorbidities were captured during TB screening and diagnosis. Laboratory exams were performed to confirm TB diagnosis and monitor ADRs, favorable (cure and treatment completion) and unfavorable (death, loss to follow up and failure) outcomes were prospectively captured. The Kaplan-Meier curve was used to estimate the probability of ADR-free time. A logistic regression analysis (backward elimination) was performed to identify independent associations with unfavorable outcomes.

Results: 550 patients were enrolled, 35.1% were people living with HIV (PLHIV) and ADR occurred in 78.6% of all participants. Smoking (OR: 2.32; 95% CI:1.34-3.99) and illicit-drug use (OR:2.02; 95% CI:1.15-3.55) were independent risk factors for unfavorable outcomes. In PLHIV, alcohol abuse and previous ART use were associated with unfavorable outcomes. In contrast, ADR increased the odds of favorable outcomes in the overall population. PLHIV more frequently experienced grade 3/4-ADR (18.36%), especially "liver and biliary system disorders". Lower CD4 counts (<100 cells/uL) were associated with hepatotoxicity (p = 0.03). ART-naïve participants presented a higher incidence of ADR in comparison with ART-experienced patients.

Conclusion: Substance use was associated with unfavorable outcomes, highlighting the need for better strategies to reduce this habit. In contrast, ADRs were associated with favorable outcomes. Attention to the occurrence of ADR in PLHIV is essential, especially regarding hepatotoxicity in those with high immunosuppression.

Copyright: © 2023 Sant´Anna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alcoholism* / drug therapy
Antitubercular Agents / therapeutic use
Brazil / epidemiology
Chemical and Drug Induced Liver Injury* / drug therapy
Drug-Related Side Effects and Adverse Reactions* / drug therapy
HIV Infections* / epidemiology
Humans
Prospective Studies
Risk Factors
Tuberculosis* / drug therapy

Substances

Antitubercular Agents

Grants and funding

This work was supported by Brazilian Program of STD-AIDS and Viral Hepatitis, in partnership with the UNODC and the Clinical Research Laboratory on Mycobacteria of INI, FIOCRUZ, edital modalidade pesquisas n° 01/2013. The study was partially supported by the Intramural Research Program of the Fundação Oswaldo Cruz. B.B.A and V.C.R. are senior scientists from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). M.B.A. received a scholarship from Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). M.A.P. received a research fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, finance code: 001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.