Treatment adherence and clinical outcomes amongst in people with drug-susceptible tuberculosis using medication monitor and differentiated care approach compared with standard of care in South Africa: a cluster randomized trial.

Background: Poor treatment adherence contributes to lower treatment completion and higher loss to follow-up among people with tuberculosis (PWTB). Medication monitors have shown some evidence of improved adherence. Methods: We conducted a cluster randomised trial in 18 primary health clinics in South Africa between May 2019-February 2022. Persons (aged ≥ 2 years) with drug-sensitive tuberculosis (DS-TB) were enrolled. All participants were provided with monitors which were silent in the standard of care (SoC) arm. In the intevention arm, weekly adherence reports were reviewed and participants received intensified support as appropriate (text, phone call, home visit, motivational counselling). The primary outcome was adherence, which was calculated as days box was opened (proxy for drug taken)/total expected treatment days as a binary variable (<80% versus ≥80%). Analysis took into account clustered design. The trial was registered with the Pan African Trial Registry PACTR20190268115772. Findings: We enrolled 2727 participants (38% women, median age 36 (IQR 27-45 years), of whom 2584 had available adherence data. The primary outcome (measured as ≥80% adherence) was higher in intervention versus SoC arm (81.0% versus 50.8%, adjusted risk ratio (ARR) 1.51 (1.36-1.66). Similarly, overall percentage adherence was higher in intervention versus SoC arm (88.5% versus 69.7%, adjusted risk difference 16.8% (13.3%-20.4%)). Interpretation: People with DS-TB had improved treatment adherence in the intervention arm. We believe the effect on adherence is important and warrants continued use and evaluation of these technologies. Funding: The study is funded by Bill & Melinda Gates Foundation, Uinted States, the Stop TB Partnership, Switzerland, and the South African Medical Research Council, South Africa.