Benefit-risk of TB prevention treatment for people with diabetes

Ending TB requires accelerated effort to intervene in people with TB-associated multimorbidity. Diabetes affects millions in poor countries and increases the risk of TB. Antibiotics to treat TB infection and prevent disease are not recommended for this risk group in settings with a high TB burden. The widely available isoniazid for 6-9 months is lengthy and the trade-off between benefit and harm perceived unfavourable. Moreover, benefit may be limited since effective risk mitigation is possible with optimal diabetes care which increasingly includes metformin, a potential host-directed therapy against TB. One-month of daily rifapentine with isoniazid (1HP) appears safe and is non-inferior to isoniazid in HIV. 1HP may alter the benefit-risk trade off to provide TPT but this unknown. In a randomised study, we will investigate 1HP safety and quantify its added benefit to reduce TB over diabetes care. This is critical to influence WHO policy and alter clinical practice We will enrol N=3,100 HIV-uninfected adults receiving standard diabetes care, have TB infection, and reside in South Africa. The study will have a safety run-in phase including the initial N=410 enrolled, and an embedded pharmacokinetic study on N=60 to characterise direct drug and drug-drug effects of 1HP in people with diabetes.