Integrating point-of-care urine isoniazid testing into routine care for tuberculosis disease in India to detect medication nonadherence and improve treatment outcomes

Tufts University Boston, Boston MA

Investigators

Abstract

Tuberculosis (TB) is the leading infectious cause of death globally. India has the largest TB epidemic, accounting for one-quarter of cases and one-third of TB deaths worldwide. Nonadherence to medications is a central challenge in TB care leading to increased death, disease recurrence, and drug resistance. Despite its importance, detecting nonadherence in routine care is challenging, as current measurement approaches are inaccurate, not person-centered, or ineffective at improving outcomes. Early and accurate detection of nonadherence may serve as an entry point for differentiated care, in which people with TB at risk for poor outcomes can be given intensified interventions. Urine isoniazid testing is a validated, low-cost, point-of-care, and direct adherence measure that may be predictive of TB outcomes and therefore serve as an ideal triage test to enable differentiated care. However, to integrate urine testing into routine care, research is needed to: (1) understand how the test performs at scheduled clinic visits, (2) gain a rich understanding of root causes of nonadherence to better leverage urine test results, and (3) identify barriers and facilitators to implementation. In this R01, we propose conducting a prospective cohort study with translational research involving clinical, behavioral, and implementation science to facilitate integration of urine isoniazid testing into India’s national TB program. Our central hypothesis is that urine testing can be integrated into routine care to facilitate early and accurate identification of people with TB who are likely to suffer poor outcomes, including death and TB recurrence. In Aim 1, we will assess the accuracy of urine test results assessed at scheduled clinic visits in comparison to those assessed at unannounced home visits. In Aim 2, we will assess the relationship between nonadherence detected by urine testing and subsequent unfavorable TB outcomes of death, loss to follow-up, treatment failure, and post-treatment TB recurrence. In Aim 3, we will identify reasons for nonadherence across the TB treatment course by conducting qualitative interviews with participants in the cohort who are urine test-negative. We will then conduct a mixed methods analysis by integrating qualitative and quantitative findings to identify interventions to improve adherence that may be appropriate at different timepoints in TB treatment. In Aim 4, we will identify implementation factors that can inform integration of urine testing into routine care by conducting qualitative interviews with people with TB in the cohort study, TB clinic care providers, and policymakers in India’s TB program. This R01 proposal aims to develop an innovative but pragmatic strategy for early identification of TB medication nonadherence that is feasible in low- and middle- income countries with a high TB burden, in a manner that aligns with the NIAID strategic objective of discovering “novel biomarkers for prediction of TB outcomes.” Our findings will inform a future R01 randomized trial in which urine testing is used to triage people with TB, to identify those at high risk, as part of an adaptive differentiated care strategy, which has great potential to improve TB outcomes in India and globally.