PROJECT ABSTRACT Tobacco use is highly prevalent among people living with HIV/AIDS (PLWH) especially in southern Africa where HIV is most heavily concentrated. Among PLWH, tobacco use impacts HIV-related co-morbidities and is the leading cause of premature mortality from non-HIV related malignancies such as lung cancer which account for 20% of the cancer burden. Integrating an evidence-based intervention, such as Screening, Brief Intervention and Referral to Treatment (SBIRT) into a HIV care system presents an important opportunity to establish and evaluate a modifiable cancer prevention strategy into a low- and middle-income country (LMIC) setting where both lay health workers (LHW) and non-physician clinicians are widely used. Botswana, where the University of Maryland Baltimore (UMB) has worked since 2015, oversees a wide network of HIV care clinics for its citizens. Demographic Health Surveys from sub-Saharan Africa show that smoking prevalence among PLWH ranges 12.5-44.3%. Yet, based on our pilot data the system of care is highly unprepared to meet the challenge of integrating evidence-based smoking cessation treatment into routine HIV care. The Government of Botswana wants more to be done to assist its citizen in smoking cessation. To meet this challenge, the Botswana Smoking Abstinence Reinforcement Trial (BSMART) proposes to use a Type 2 hybrid effectiveness-implementation study design to evaluate the effectiveness and implementation of a well-established SBIRT intervention consisting of the 5As, (Ask, Advise, Assess, Assist, Arrange) delivered by trained LHW case managers, followed by referral to treatment with varenicline (a medication demonstrated to be efficacious for smoking cessation among PLWH1-3 and on formulary in Botswana) prescribed and monitored by trained nurse prescribers-dispensers, in the network of outpatient HIV care facilities in Botswana. The specific aims guided by the RE-AIM Framework and informed by an Implementation Governance Structure are to: 1) Assess Reach and Effectiveness of BSMART; 2) Assess the Adoption and Implementation indexed by quality and consistency of intervention delivery; 3) Assess whether the intervention becomes Maintained as part of routine practices; 4) Determine the preliminary cost-effectiveness of BSMART.