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

Open Forum Infect Dis. 2021 May 5;8(6):ofab190. doi: 10.1093/ofid/ofab190. eCollection 2021 Jun.

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 nonadherence.

Methods: We enrolled adult drug-susceptible TB patients, approximately half of whom were people with human immunodeficiency virus (PWH), in Chennai, Vellore, and Mumbai. We conducted a single unannounced home visit to administer a survey assessing reasons for nonadherence and collect a urine sample that was tested for isoniazid content. We described patient-reported reasons for nonadherence and identified factors associated with nonadherence (ie, negative urine test) using multivariable logistic regression. We also assessed the association between nonadherence and treatment outcomes.

Results: Of 650 participants in the cohort, 77 (11.8%) had a negative urine test. Nonadherence was independently associated with daily wage labor (adjusted odds ratio [aOR], 2.7; confidence interval [CI], 1.1-6.5; P = .03), the late continuation treatment phase (aOR, 2.0; CI, 1.1-3.9; P = .03), smear-positive pulmonary disease (aOR, 2.1; CI, 1.1-3.9; P = .03), alcohol use (aOR, 2.5; CI, 1.2-5.2; P = .01), and spending ≥30 minutes collecting medication refills (aOR, 6.6; CI, 1.5-29.5; P = .01). People with HIV reported greater barriers to collecting medications than non-PWH. 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 nonadherence (P < .0001).

Conclusion: Addressing structural and psychosocial barriers will be critical to improve TB treatment adherence in India. Urine isoniazid testing may help identify nonadherent patients to facilitate early intervention during treatment.

Keywords: HIV; India; adherence; alcohol use; tuberculosis.