Title: Effects of e-cigarettes (ECIGs) on pulmonary inflammation and behavior in HIV infected smokers

Purpose of the Study: Even though smoking is the leading cause of preventable disease and deaths in the U.S., millions of Americans continue to smoke cigarettes, including 16% of persons in the general population and 40-70% of all HIV-infected patients. In contrast to the relatively known adverse effects of combustible cigarettes, the rapid emergence of e-cigarettes have raised numerous questions regarding their health effects which may be amplified in vulnerable populations and those already immunocompromised such as HIV-infected patients. The goal of the proposed research is to gain an understanding of the cellular and inflammatory mechanisms that occur in the lung of HIV-infected smokers who transition from conventional tobacco cigarettes to e-cigarettes and to characterize their behavioral and neurocognitive effects. These efforts will provide first in kind data on the effects of ECIGs in this study population and provide valuable data to develop needed regulatory policies.

Background \& Significance: While rates of cigarette smoking are gradually decreasing in the US, the burden of tobacco abuse among people living with HIV remains undisputedly high with prevalence estimates two to three times higher than the general population (42.4% vs. 16%). Although ECIGs likely contain significantly fewer numbers of toxicants compared to combustible cigarettes, it is not yet clear whether ECIG are less harmful than their traditional tobacco counterparts and what, if any, effects they have on behavior and neurocognitive functioning. The biological effects of ECIG on lung health have not yet been sufficiently characterized due the relatively nascent nature of the field. While combustible tobacco use induces oxidant stress in the airways of healthy smokers, little work to date has established the effect of ECIG use on oxidant stress in human airways. Transitioning the smoker from combustible tobacco to ECIG may decrease lung oxidative stress, improve lung function and decrease withdrawal symptoms and deficits in neurocognition commonly seen with tobacco withdrawal.

Design \& Procedures: 15 HIV-infected adults will be recruited from the Duke Infectious Diseases Clinic. In addition, 5 HIV-negative adults will be recruited from the community through flyers. For this pilot study, 15 willing subjects will receive ECIGs and 5 control subjects will continue to smoke their chosen usual brand of combustible cigarettes (UB). Each group will receive either ECIG or UB for a total of 4 weeks and undergo pulmonary and behavioral assessments during this period. In order to examine pulmonary and behavioral effects of ECIG in the absence of combustible cigarette use, a mobile contingency management (mCM) procedure will be used to provide monetary reinforcement for biochemically verified discontinuation of the use of combustible cigarettes. Participants in the UB group will also undergo mCM procedures, but contingencies will differ. After 4 weeks, the ECIG group will be allowed to transition back to their chosen combustible cigarette product for an additional 2 weeks with additional pulmonary and behavioral assessments. All subjects will undergo three respiratory assessments in the Duke Clinical Research Unit (DCRU). The first respiratory assessment will occur at study arm assignment (V1) to establish baseline measures of lung function, oxidative stress, and systemic inflammation. Pulmonary assessments will be repeated again 4 weeks after transition to ECIG or continued UB use (V4). A final respiratory assessment (V5) will occur 2 weeks after stopping ECIG or after 6 weeks of continued UB use to measure changes relative to baseline lung function, oxidative stress, and inflammation. Neuro-cognitive and behavioral visits will take place in Duke South or at the Center for Addiction Science and Technology (CfAST) and occur at Visit 2 (mCM transition), and respiratory visits (V4 \& V5) as well as 2 weeks after ECIG transition/ continued UB use (V3)