Patterns of Treatment Interruption among Patients with Multidrug-Resistant TB (MDR TB) and Association with Interim and Final Treatment Outcomes

BACKGROUND The reasons that patients with multidrug-resistant tuberculosis (MDR TB) miss treatment are multi-factorial and complex. Identifying patterns of treatment interruption that predict poor outcomes can be used to target program activities aiming to improve treatment adherence. OBJECTIVE To characterize patterns of treatment interruption among MDR TB patients and determine the association between patterns and treatment outcomes. METHODS Retrospective analysis of MDR TB patients. A treatment interruption was defined as any time that a patient missed a prescribed dose of treatment for at least 1 day but for a period of less than 2 consecutive months. Patients were characterized by the number, length and variability of interruptions, variability of time between interruptions, and percent of missed doses. Final treatment outcome was dichotomized as a successful (cured or completed) or poor outcome (defaulted, failed, or died). Risk ratios were calculated to determine the association between characteristics of treatment interruption and treatment outcomes. All analyses were conducted in 6 month treatment intervals. RESULTS Only 7.0% of 583 patients completed treatment without interruption. Of the remaining 542 patients, the median time to the first interruption was 2 ½ months (70 days). In multivariate analysis, patients who had longer interruptions with sporadic variability during the 6-12 month or the 12-18 month treatment period had a significantly increased risk for poor outcomes compared to patients who had short, regular interruptions (RR(adj) 4.37, 95% CI 1.2-15.8;  = 0.03 and RR(adj) 3.38, 95% CI 1.6-7.1; p = 0.001, respectively). In addition, missing 10% or more of the prescribed doses during any 6 month period in the initial 18 months of therapy significantly increased the risk for poor outcomes (RR(adj) range 1.55-2.35; p-value range 0.01-0.005). CONCLUSION Patients that miss more consecutive days of treatment with sporadic interruption patterns or a greater proportion of treatment are at an increased risk for poor treatment outcomes.