ABSTRACT Cigarette smoking is disproportionately prevalent among persons with HIV as compared to the general population. Currently, smoking is responsible for a greater loss of life years than is HIV itself in this population. Many HIV-positive smokers report a desire to quit but are unable to do so. Poor cessation rates in this population are likely due in part to suboptimal adherence to smoking cessation medications. Mobile technologies, like smartphones, are increasingly ubiquitous and affordable in the U.S., and can be integrated to augment medication adherence. Mobile phone-delivered interventions show promise at improving cessation outcomes relative to usual care in smokers living with HIV. However, the only existing trial to attempt to improve adherence to smoking cessation medication among smokers living with HIV has yielded null results. It is possible that smokers living with HIV may require an additional behavioral component to improve the effectiveness of mobile-phone-based interventions. Thus, we propose to evaluate mSMART, an existing smartphone application that targets medication adherence, in combination with contingency management (CM)—a behavioral intervention shown to improve outcomes for clinically relevant behaviors such as HIV medication adherence and smoking cessation—to improve adherence to varenicline among smokers with HIV. The overarching goal of the research proposed in this application is to develop and evaluate an intervention that targets adherence to varenicline, with the goal of improving adherence and cessation outcomes among smokers living with HIV. The proposed research study has the following specific aims: 1) To conduct formative interviews with smokers living with HIV; 2) To conduct a proof-of-concept trial of mSMART and mSMART+CM; and 3) To characterize determinants of varenicline adherence. The proposed research builds upon the Principal Investigator's previous experience and is closely aligned with her overarching career development goal of becoming an independent investigator with expertise in the development and evaluation of treatments for smoking cessation among smokers living with HIV. Dr. Pacek is a postdoctoral associate at the Duke University Medical Center with expertise in the epidemiology of smoking in persons living with HIV and behavioral pharmacology of smoking. The primary training goals of this proposal are to gain skills in clinical trials research methodology and mobile health intervention development, and develop content expertise in medication adherence. The results of the proposed research and training plans will facilitate Dr. Pacek's development as an independent investigator and provide preliminary data for a future large-scale efficacy study.