Factors Associated with Discontinuation of Tuberculosis Preventive Treatment: Post-Hoc Analysis of Two Randomized Controlled Trials.

BACKGROUND: Adherence to tuberculosis preventive treatment (TPT) is an important determinant of clinical benefit. We assessed the association of participant behaviors early in TPT with subsequent discontinuation.

METHODS: We used data from a phase 3 randomized trial, and preceding phase 2 trial, comparing four-months rifampin to nine-months isoniazid for TPT. We excluded participants whose providers discontinued TPT due to adverse events or tuberculosis disease. We analyzed four outcomes: discontinuing TPT within the first month of treatment, between the first and second month, after the second month, and completing treatment, but not per protocol. We analysed the association of outcomes with regimen and participant characteristics and four behavioral predictors of discontinuation recorded at the month 1 and month 2 follow-up visits: reporting symptoms of intolerance, missing >20% of doses, rescheduling appointments, and not bringing their medication bottle.

RESULTS: Overall, 6656 participants were included (Phase 3, 5848; Phase 2, 808); of whom 4318 (64.9%) completed treatment per protocol. Participant characteristics were inconsistently associated with discontinuation. Phase 3 trial participants with one, two, or three-four behavioral predictors at the month one follow-up had 5.0 (95%CI 3.6-6.7), 18.6 (13.3-26.1), and 79.4 (38.2-165.0), respectively, higher odds of discontinuing before the second month. The corresponding number of predictors at the month two follow-up had 1.8 (1.4-2.2), 4.7 (3.6-6.2) and 7.4 (4.6-11.9) higher odds of discontinuing before completing treatment. Phase 2 findings were similar.

CONCLUSIONS: Four behavioral predictors recorded early in therapy were more strongly associated with subsequent discontinuation than participant characteristics, particularly when more than one behavioural predictor was recorded.Clinical trials registration: (NCT00170209; NCT00931736).