Temporal complexity in missed doses of rifampicin-sensitive anti-tuberculosis treatment: a prospective cohort study in Tanzania

Background: Non-adherence to anti-tuberculosis (TB) regimens is not simplistic; rather, doses are missed in complex patterns. In a cohort of individuals being treated for rifampicin-sensitive pulmonary TB in Tanzania, we sought to examine how doses were missed across the treatment course and within a day, as well as the reasons for missed dose periods.

Methods: 200 participants aged ≥18 years treated with the standard six-month regimen were recruited March 2022-June 2023. Missed doses were measured using evriMED pillboxes and by pill count. The reasons for up to three missed dose periods per month were collected. Patterns of missed doses- across treatment and within a day- and their reasons were visualised and 44 described.

Findings: Two participants died early in treatment, leaving 198 with missed dose data. The increase in the percentage of participants that missed any given dose as time progressed was driven by early discontinuation (median doses missed 0.0% in month 1 vs. 6.7% in month 6) from treatment, as opposed to sporadic missed doses (median doses missed 3.1% in month 1 vs. 4.1% in month 6). There was a median of one sporadic missed dose period (ranging between 0 and 42 doses in length) per participant. Out of all reported reasons for missed dose periods, 53 forgot or forgot and inconvenience were the most common (59.6%).

Interpretation: Missing doses of anti-TB treatment is a temporally complex phenomenon and the result of the intersection of multifaceted day-to-day events in an individual’s life, with complicated implications for effective drug levels across the treatment course. This complexity limits our ability to predict an individual’s missed doses at the start of treatment.