MD PhD Alain Amstutz

Reduce Tobacco Use in People Living with HIV in Switzerland (RETUNE)

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:

Improving the HIV care cascade in Lesotho: Towards 90-90-90 - A research collaboration with the Ministry of Health

Background: Despite enormous progress in the last decade, HIV/AIDS remains the most important cause of morbidity and mortality in most countries of Southern Africa and a central contributor to economic underdevelopment and poverty in many societies. The 2014 UNAIDS "90-90-90" targets for 2020 represent an important step towards an AIDS-free generation by 2030. The targets emphasize the importance of antiretroviral therapy (ART) to prolong the life of people living with HIV and as the most effective preventative measure for reducing the spread of new infections through better virus control. The three key targets of "90-90-90" are: - 90% of all people living with HIV will know their HIV status. - 90% of all people with diagnosed HIV infection receive treatment. - 90% of all people receiving therapy will have their virus suppressed.

This project represents a collaboration between the Research Coordination Unit (RCU) of the Ministry of Health (MoH) of Lesotho, the District Health Management Team (DHMT) of Butha-Buthe, SolidarMed (Lesotho-based Swiss organization for health in Africa), the Swiss Tropical and Public Health Institute (SwissTPH) and the Molecular Virology unit at the Department of Biomedicine (DBM) of the University of Basel. The project combines epidemiological, operational and clinical research to address key questions related to reaching 90-90-90 targets in rural Lesotho, a country with the second-highest HIV prevalence in the world, high transmission rates and low ART coverage.

Methods: The proposed project is planned in Butha-Buthe district, Northern Lesotho, involving 2 hospitals and 10 health centers. As a crucial first step, the project has established the technical basis for the intended studies. As part of Lesotho's national viral load (VL) roll-out plan, the country's first decentralized VL monitoring platform was installed in the district laboratory of Butha-Buthe by the end of October 2015. Two randomized controlled trials (RCTs) and additional observational studies are planned within the proposed project.

RCT-1 (CASCADE-trial; NCT02692027, www.visibleimpact.org/projects/1197-cascade-trial) addresses the care-cascade from HIV-test to linkage to care to retention in care and achievement of viral suppression in the era of test-and-treat. Individuals who are newly tested HIV-positive during home-based HIV testing and counseling (HTC) are randomized into 2 groups. The control group provides standard of care with post-test counseling and a referral letter for enrolment in pre-ART care at the nearest facility. In the intervention-group, baseline laboratory testing and adherence counseling is provided after a positive HIV test at the participant's home with the option to start ART on the same day. The first primary endpoint is linkage to care at the facility within 3 months. The secondary endpoint is retention in care and viral suppression 12 months after HIV diagnosis. This trial has two nested observational studies. The first examines HTC-coverage achieved through home-based HTC while recruiting trial-participants. The second examines glucose- and lipid-profiles pre-ART and after ART initiation.

RCT-2 (SAVIR-trial): A culturally adapted, short, standardized adherence intervention for patients on ART with unsuppressed VL will be rolled out to the facilities in the district using a step-wedged design with the primary endpoint of VL re-suppression at follow-up determination. Establishing routine viral load monitoring will be linked to a database, a plasma-bank and introduction of genotypic sequencing in the district. This will allow observational studies on roll-out of viral load monitoring, treatment failure, switch to second-line ART and HIV resistance. Based on these observational data, a protocol for a third RCT will be elaborated by end of 2016. This RCT will address challenges identified in the field of treatment failure and switch to second-line ART.

EU-RESPONSE is a 5-year project that includes two European Adaptive Platform Trials: DisCoVeRy and EU-SolidAct. The EU-RESPONSE consortium is composed of 22 partners, bringing together multidisciplinary partners from across the continent.

The group at the Division of Clinical Epidemiology is part of the methods and statistical group and co-leads specific meta-research projects such as several individual participant data meta-analyses (IPDMAs).