Project Summary/Abstract Tuberculosis (TB) is the leading cause of death among people living with HIV (PLHIV), responsible for over one-third of all HIV deaths worldwide. Tuberculosis preventive therapy (TPT), which can reduce TB incidence by 30-50%, is recommended for all PLHIV by the World Health Organization (WHO). Although a new 12-dose, once-weekly regimen of isoniazid and rifapentine (3HP) via directly observed therapy (DOT) is now available and recommended, treatment completion remains a concern. Additionally, DOT is not a feasible strategy for increasing TB preventive therapy uptake in high burden, low-income settings. To realize the promising potential of 3HP to reduce TB mortality among PLHIV, there is an urgent need for studies that evaluate approaches to support treatment completion with self-administered therapy. The overall objective of this proposal is to determine whether low-cost digital adherence technologies (DATs) can be used to monitor and support completion of 3HP among PLHIV. Our central hypothesis is that a theory- informed adaptation of DATs to fit users' needs will result in high levels of DAT adoption and implementation fidelity. This hypothesis is based on preliminary data from my work in using human-centered design (HCD) methods to adapt a DAT platform to address the adherence challenges faced by patients with active TB. In my mentor's stepped wedge randomized trial, this adapted DAT platform had high levels of acceptability for patients and providers, and improved completion of treatment for active TB. The proposed studies will build upon this prior work to support the use of DATs for scaling-up TB preventive therapy to a key high-risk population. To test this hypothesis in Aim 1 I will identify barriers and facilitators to the use of DATs for facilitating 3HP completion among PLHIV. In Aim 2 I will then adapt two low-cost DATs to fit users' needs using the human centered design methodology. Last, in Aim 3, I will conduct pilot trials to assess the preliminary effectiveness and implementation of each adapted DAT among PLHIV initiating 3HP. The results will provide the preliminary data needed for an NIH R01 application proposing a randomized trial to evaluate the effectiveness, implementation, and cost-effectiveness of one or both contextually adapted DATs for supporting completion of short-course TB preventive therapy among PLHIV. The proposed research aims map directly onto my training objectives including designing implementation interventions using mixed methods research (Aims 1 & 2), tailoring implementation interventions using human- centered design (Aim 2), and evaluating implementation interventions (Aim 3). Rigorous implementation science-focused training coupled with an interdisciplinary mentorship team committed to my success will catalyze me towards my career goal to become an independent physician-scientist focused on improving uptake of evidence-based interventions to reduce TB burden among PLHIV.