PROJECT SUMMARY Global health organizations have called for integrating tobacco control into HIV and tuberculosis (TB) responses. Tobacco use worsens health outcomes of people with HIV, including conferring higher risks of TB and of noncommunicable diseases such as cardiovascular disease and cancer. How to most effectively and efficiently incorporate tobacco control into HIV and TB care remains unclear; resource constraints necessitate thoughtful and evidence-based planning. Determining which interventions are most effective and cost-effective, and how to combine delivery approaches for optimal outcomes, is critically important for informing clinical guidelines. This requires understanding the benefits and costs of various interventions, which cost- effectiveness modeling is specifically designed to address. The overall goal of this proposal is to promote an evidence-based approach to decisions surrounding the integrated care and services for the overlapping tobacco, HIV, and TB epidemics in low- and middle-income countries (LMICs). Tobacco use and cessation behaviors in LMICs may differ from those in high-income countries and can influence the effectiveness of interventions. In this proposal, we will focus on South Africa, a country with colliding tobacco, HIV, and TB epidemics. Our research plan includes: developing an integrated simulation model of tobacco, HIV, and TB; parameterizing the model with behavioral, clinical, and cost data from a community-based population cohort in South Africa and from other databases and studies; projecting clinical and economic outcomes associated with tobacco use and cessation among people with HIV; and conducting model-based cost-effectiveness analysis of tobacco cessation interventions, including those combined with other HIV and TB care interventions. This proposal brings together internationally recognized experts in fields that are complementary for the project, including clinical policy-relevant HIV and TB simulation modeling, health behaviors, tobacco treatment interventions, and epidemiology of HIV and comorbidities in South Africa. The investigators and institutions have a history of highly productive collaboration. The innovative model will be the first to integrate tobacco, HIV, and TB. The methods are highly significant and crucial for addressing questions around cost- effectiveness and policies for integrating tobacco cessation with HIV and TB care. The model structure will enable future analyses of tobacco cessation interventions in other settings, establishing a broad, durable framework for policy-relevant clinical and health economic analyses.