Understanding Nonadherence to Tuberculosis Medications in India Using Urine Drug Metabolite Testing: A Cohort Study

Abstract

Background Poor adherence to tuberculosis (TB) treatment is associated with disease recurrence and death. Little research has been conducted in India to understand TB medication non-adherence. Methods We enrolled adult drug-susceptible TB patients, about half of whom were people living with HIV (PLHIV), in Chennai, Vellore, and Mumbai. We conducted a single unannounced home visit to administer a survey assessing reasons for non-adherence and collect a urine sample that was tested for isoniazid content. We described patient-reported reasons for non-adherence and identified factors associated with non-adherence (i.e., negative urine test) using multivariable logistic regression. We also assessed the association between non-adherence and treatment outcomes. Results Of 650 participants in the cohort, 77 (11.8%) had a negative urine test. Non-adherence was independently associated with daily wage labor (aOR 2.7, CI: 1.1—6.5, p=0.03), the late continuation treatment phase (aOR 2.0, CI:1.1—3.9, p=0.03), smear-positive pulmonary disease (aOR 2.1, CI: 1.1—3.9, p=0.03), alcohol use (aOR 2.5, CI: 1.2—5.2, p=0.01), and spending >=30 minutes collecting medication refills (aOR 6.6, CI: 1.5—29.5, p=0.01). PLHIV reported greater barriers to collecting medications than non-PLHIV. Among 167 patients reporting missing doses, reported reasons included traveling from home, forgetting, feeling depressed, and running out of pills. The odds of unfavorable treatment outcomes were 4.0 (CI: 2.1—7.6) times higher among patients with non-adherence (p<0.0001). Conclusion Addressing structural and psychosocial barriers will be critical to improve TB treatment adherence in India. Urine isoniazid testing may help identify non-adherent patients to facilitate early intervention during treatment.

Measuring tuberculosis medication adherence: a comparison of multiple approaches in relation to urine isoniazid metabolite testing within a cohort study in India

“…During August 2017 to February 2019, we sequentially recruited people with drug-susceptible TB who were ≥18 years of age and eligible for 99DOTS monitoring [ 4 , 15 ]. Participants were recruited during clinic visits to start TB treatment or collect medication refills, excluding those in the last treatment month (to allow time for study procedures).…”

“…At enrollment, we consented participants for a future unannounced home visit and administered a socio-behavioral questionnaire [ 4 ]. We conducted the home visit at least 3 weeks after enrollment, or after the start of the continuation phase for participants randomized to undergo the home visit in that phase.…”

“…At the visit, we administered an adherence questionnaire and collected a urine sample for isoniazid metabolite testing. Although the single visit limits understanding of adherence throughout treatment for individual participants, the visits provide information distributed throughout the treatment course for the sample as a whole [ 4 ].…”

“…In clinical trials, missing >10% of doses during TB therapy is associated with ~6 times increased risk of poor outcomes [ 2 ]. Similarly, in India’s TB program, poor adherence has been associated with higher unfavorable treatment outcomes and disease recurrence [ 3 , 4 ].…”

“…In this manuscript, we compared multiple measures of adherence to drug-susceptible TB therapy through secondary analysis of a cohort study conducted in India. Primary findings from this cohort study have been published previously [ 4 , 15 ]. We conducted a single unannounced home visit for each participant, during which we collected a urine sample that was tested for isoniazid metabolites.…”