[FG] Labhardt Niklaus

Tobacco smoking represents a leading health burden in the aging population of people living with HIV in Switzerland. New tools for smoking cessation like electronic cigarettes or nicotine pouches are promising to reduce the harm caused by tobacco smoking. However, high quality evidence of their effectiveness among people living with HIV and outside of explanatory randomized trials is missing. 

RETUNE is a highly pragmatic randomized trial, fully embedded in the Swiss HIV Cohort Study (SHCS), using the “Trials within Cohorts” (TwiCs) design. 

In the TwiCs design, participants are recruited within a prospective cohort study and can consent not only to regular data collection at cohort visits, but also to be randomized in future low-risk pragmatic trials (“randomization consent”). Participants are informed that only participants randomized to the intervention arm are approached and may then accept or decline the offered intervention. Participants in the intervention who accept the intervention, are asked to sign an “intervention consent”, that only covers additional data collection in this group and the safety/side-effects of the intervention – similar to a routine clinical consent (e.g. consent for a lumbar puncture in clinical care). 

RETUNE aims to assess the effectiveness of the offer of a menu including different tobacco cigarettes substitutional products (e-cigarettes, nicotine pouches, nicotine patches) to quit smoking. People with HIV in the SHCS who smoke tobacco cigarettes and who signed the randomization consent will be randomized in a 1:1 ratio to the offer of the menu or to usual care. People are included regardless of their willingness to quit smoking. The primary endpoint is tobacco abstinence after 6 months. RETUNE is a multicenter trial which will include centers in Basel, Bern, Geneva, Lausanne, St. Gallen, and Zurich. 

RETUNE is funded by the Tobacco Prevention Fund, the Novartis foundation for medical-biological research, and the Swiss National Science Foundation.

Involved partner:

SaDAPT is a randomized controlled trial in Lesotho and Malawi investigating when to start antiretroviral therapy in persons testing positive for HIV and simultaneously showing symptoms of a possible TB infection.

Rapid, if possible same-day initiation (SDI) of antiretroviral therapy (ART) is recommended for all persons living with HIV (PLHIV) without contraindication who are ready to start treatment. A possible contraindication to initiating ART is the presence of an untreated tuberculosis (TB) infection as it increases the risk of TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) after ART initiation. In case of TB symptoms (presumptive TB), previous guidelines recommended to postpone ART initiation until investigations for active TB infection have been completed to avoid initiating ART in presence of untreated TB and thus reduce the risk of TB-IRIS. However, the 2021 guidelines of the World Health Organization (WHO) changed to recommending rapid or SDI even in case of TB symptoms without awaiting results of TB diagnostic tests based on the assumption that TB tests often unnecessarily delay ART initiation increasing the risk for pre-ART attrition from care while the clinical relevance of TB-IRIS outside the central nervous system remains unclear. To date, there is no conclusive evidence about whether SDI of ART or TB test results should be prioritized in PLHIV with presumptive TB.

SaDAPT is a two arm, individually randomized, pragmatic trial comparing two approaches for the timing of ART initiation in PLHIV with presumptive TB (“ART first” versus “TB results first”). PLHIV in Lesotho and Malawi, aged 12 years and older (re)initiating ART who have at least one of TB symptom (cough, fever, night sweats or weight loss) and who do not have signs of meningitis are eligible. Participants in the “ART first” arm will be offered SDI of ART while those in the “TB results first” arm will be offered ART only after results of TB tests are available.

We hypothesize that the “ART first” approach is safe and non-inferior to the “TB results first” approach with regard to HIV viral suppression (<400 copies/ml) six months after enrollment. Secondary outcomes include retention in care and adverse events consistent with TB-IRIS.