Offer of a menu of different nicotine substitute products to REduce Tobacco Use iN pEople living with HIV (RETUNE): a protocol for a pragmatic randomized trial within the Swiss HIV Cohort Study

Abstract Background Among people living with HIV, there has been a shift of focus from HIV-related health issues to cardiovascular diseases and cancer. For both, tobacco smoking is a major but insufficiently addressed etiological factor. Evidence from randomized trials suggests that nicotine substitute products such as e-cigarettes and nicotine patches can reduce tobacco smoking and its associated health burden. However, most previous smoking cessation trials primarily included people who are motivated to quit smoking and focused on testing a single nicotine substitute product. The effectiveness of offering a menu of nicotine substitute products to tobacco smokers regardless of their willingness to quit smoking (“opt-out” approach) is unknown. Methods Reduce tobacco use in people living with HIV in Switzerland (RETUNE, NCT06789692) is a pragmatic, 1:1 randomized, multicenter, superiority clinical trial using the Trials within Cohorts (TwiCs) design within the Swiss HIV Cohort Study. RETUNE assesses the effectiveness of offering a menu of different nicotine substitute products, namely electronic cigarettes, nicotine pouches, and nicotine patches, versus usual care. Cohort participants are eligible if they smoke more than one tobacco cigarette per day, do not use any of the substitute products, and have signed the randomization consent following the TwiCs design. Participants randomized to the intervention may choose any of the offered substitutes to be used free of charge for 6 months or decline the offer. Overall, we plan to recruit 972 participants. The primary outcome is tobacco abstinence at 6 months measured as participant-reported past 7-day prevalence abstinence. The primary outcome will be assessed in the intention-to-treat set using a logistic regression model adjusted for region, men having sex with men, current drug users, and number of cigarettes per day at baseline. Secondary outcomes are long-term smoking cessation rates and tobacco-associated health outcomes. Discussion RETUNE started recruitment in February 2025 and is currently ongoing. RETUNE using the TwiCs design will clarify the effectiveness of a preference-based opt-out smoking cessation intervention among people living with HIV. Trial registration Clinicaltrials.gov NCT06789692. Registered on January 17th, 2025. The manuscript is aligned with the registry. https://clinicaltrials.gov/study/NCT06789692?cond=NCT06789692&rank=1