Cigarette smoking is the leading cause of death and disability in the United States (U.S.), contributing to over 440,000 deaths each year. Still, over 40 million adults in the U.S. currently smoke despite well-established links to morbidity and mortality. Studies suggest HIV+ adults are at a higher risk for being current smokers and that quitting smoking may be particularly difficult for individuals with anxiety problems. Although panic and related anxiety disorders frequently co-occur with smoking and are prevalent among persons living with HIV, there has been very little attention given to improving cessation outcome among this high-risk group of HIV+ smokers. This neglect sits on the backdrop of a larger issue in the smoking cessation literature: a general lack of innovation in efficacious psychosocial treatments for nicotine dependence, particularly among persons living with HIV. Researchers have frequently called attention to the links across smoking and anxiety-related states. Recent evidence suggests that anxiety disorders and related anxiety vulnerability factors, specifically anxiety sensitivity (or fear of somatic arousal), negatively impact cessation. These findings indicate that there is clinical and theoretical merit to targeting anxiety symptoms among HIV+ smokers to improve cessation outcomes. A growing body of work suggests that anxiety disorders can be effectively treated with transdiagnostic cognitive behavioral treatment (CBT). Accordingly, we are proposing a 3-year study to develop an integrated treatment for smoking cessation for anxiety-vulnerable HIV+ smokers. The intervention development approach will follow a staged model consistent with NIH guidelines for developing and standardizing behavioral interventions, with the proposed research representing a Stage IB study. Specifically, during the first year, startup activities will include piloting the integrated intervention on a subset of individuals (N = 12), soliciting internal and external expert consultant and participant feedback, and development of the final treatment manual and procedures. The goal during this phase will be to establish feasibility of treatment delivery, participant acceptability, and potential for an effect. During the following two years, a small two-arm efficacy study (N = 60) will be undertaken comparing the new intervention to a control intervention. This study represents an important step in the larger landscape of translating basic research to more efficacious strategies for treating nicotine dependence in HIV. This study addresses an important public health issue by assessing an intervention that may lead to a more effective application for the treatment of at-risk HIV+ smokers. The expected findings should: (1) Guide advances in the theoretical conceptualization of the mechanisms involved in HIV-anxiety-smoking relations. (2) Directly inform the development of a novel and psychosocial/behavioral and pharmacological smoking cessation intervention(s) for HIV+ smokers with anxiety disorders. This is an interdisciplinary research proposal that involves collaboration between clinical psychologists, physicians, and mental health/HIV counselors. PUBLIC HEALTH RELEVANCE: This trial will provide important information regarding the potential efficacy and mechanisms of an integrated intervention for and at risk group of HIV+ smokers, namely those who also have clinically significant anxiety problems (>60% of HIV+ smokers). Identifying efficacious treatments for smoking cessation for HIV+ adults has considerable public health significance because cigarette smoking is the leading cause of death and disability in the United States (U.S.), contributing to over 440,000 deaths each year, and HIV+ smokers comprise an overrepresented group among smokers. Moreover, this study will guide advances in the theoretical conceptualization of the mechanisms involved in HIV-anxiety- smoking relations.