Adverse Drug Reactions in Tuberculosis Treatment: Incidence, Duration and Resolution Pathways from a Mixed-Methods Patient-centric Study in India
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Adverse drug reactions (ADRs) remain a major barrier to successful tuberculosis (TB) treatment. They undermine adherence, prolong morbidity, and increase the risk of treatment failures and mortality. Yet, evidence on their incidence, duration, and management across diverse patient groups remains limited. We conducted a mixed-methods study to address this gap, using a representative sample of patients from six states in India. Specifically, we combined ethnographic observations and interviews with 40 patients and stakeholders across three districts with a quantitative survey of 2,000 randomly selected TB patients across eight districts. The ethnographic analysis revealed a novel taxonomy of ADRs, distinguishing active ADRs (acute, clinically urgent conditions), from passive ADRs (persistent, lower-intensity conditions) that quietly undermine adherence in later treatment phases. Passive ADRs such as skin darkening and fatigue typically warrant little clinical attention, yet their persistence makes them highly relevant for patient management strategies aimed at supporting adherence and achieving TB elimination. This finding was further contextualized and strengthened by quantitative analysis, which provided robust statistical insights into their incidence across diverse patient profiles. The quantitative analyses also reveal a near-universal burden of ADRs, with 86% of patients reporting at least one ADR (Mean = 3.1, SD 2.38). Women reported ADRs more frequently and for longer durations, particularly cutaneous ADRs, while elderly patients were more prone to gastrointestinal and musculoskeletal ADRs. Younger patients and women reported the highest prevalence of vomiting (41%), which emerged as the only independent predictor of unsuccessful treatment completion (OR = 0.39, 95% CI: 0.20–0.76). The overall number of ADRs was also strongly correlated with adverse treatment outcomes (OR = 0.88, 95% CI: 0.78–0.98). The active-passive taxonomy, along with risk-group profiling, offers a roadmap for differentiated counselling and pro-active patient-centric ADR management. We recommend embedding this approach into national TB protocols, with structured risk-based patient counselling at different stages of treatment, supported by adequate training for treatment coordinators and providers. While further research is warranted to assess scalability and cost-effectiveness, our findings demonstrate both the urgency and the feasibility of structured ADR management in high-burden TB settings.
Author Summary
Adverse drug reactions (ADRs) among drug-sensitive TB patients pose a significant challenge in TB treatment, particularly in resource-constrained settings. Yet, literature on their incidence, duration and resolutions pathways remains scarce - especially studies documenting these across socio-demographic profiles. Our study addresses this gap using a sequential mixed-methods design, combining qualitative and quantitative methodologies. The approach contributes two key advances to the literature. First, it introduces a novel taxonomy of ADRs, grounded in patients’ lived experiences and the support received. This taxonomy segregates ADRs into “active” ADRs, which are more severe and require urgent medical attention, and “passive” ADRs, which are less severe but persist for a longer time, and quietly undermine adherence. Second, it provides statistically validated evidence on the incidence, duration, and resolution of eleven ADRs, disaggregated across socio-demographic profiles. Together, these findings provide a roadmap for developing differentiated, risk-tailored protocols that emphasize gender- and age-responsive counselling. We recommend adapting these insights to inform dedicated ADR guidance within the National TB Elimination Frameworks (NTEP) for India, as well as other high-burden countries, clearly outlining the roles and responsibilities of healthcare providers - particularly treatment coordinators and physicians - and supporting them through targeted training led in collaboration with the NTEP.
