Evaluating smoking cessation interventions for people living with HIV in a factorial randomised clinical trial in South Africa using the Multiphase Optimization Strategy (MOST) framework: The Tlogela Trial protocol

Leisha P Genade; Laura Steiner; Firdaus Nabeemeeah; Raymond S Niaura; Bareng A S Nonyane; Christopher J Hoffmann; Hojoon Sohn; Christopher G Kemp; Kate Guastaferro; Lebohang Mlambo; Deshan Chetty; Ziyaad Waja; Neil Martinson; Jonathan E Golub; Jessica L Elf

doi:10.1016/j.cct.2025.107985

Evaluating smoking cessation interventions for people living with HIV in a factorial randomised clinical trial in South Africa using the Multiphase Optimization Strategy (MOST) framework: The Tlogela Trial protocol

Contemp Clin Trials. 2025 Jun 19:155:107985. doi: 10.1016/j.cct.2025.107985. Online ahead of print.

Authors

Affiliations

¹ Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Post Office Box 114, Diepkloof, Johannesburg, South Africa. Electronic address: genadel@phru.co.za.
² Johns Hopkins University, School of Medicine, 1550 Orleans St, Baltimore, MD 21231, USA. Electronic address: lsteine5@jhmi.edu.
³ Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Post Office Box 114, Diepkloof, Johannesburg, South Africa. Electronic address: nabeemeeahf@phru.co.za.
⁴ New York University, School of Global Public Health, 708 Broadway, New York, NY 10003, USA. Electronic address: niaura@nyu.edu.
⁵ Johns Hopkins Bloomberg School of Public Health, Department of International Health, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: bnonyan1@jhu.edu.
⁶ Johns Hopkins University, School of Medicine, 1550 Orleans St, Baltimore, MD 21231, USA. Electronic address: choffmann@jhmi.edu.
⁷ Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, South Korea. Electronic address: hsohn@snu.ac.kr.
⁸ Johns Hopkins Bloomberg School of Public Health, Department of International Health, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: ckemp11@jhu.edu.
⁹ New York University, School of Global Public Health, 708 Broadway, New York, NY 10003, USA. Electronic address: kate.guastaferro@nyu.edu.
¹⁰ Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Post Office Box 114, Diepkloof, Johannesburg, South Africa. Electronic address: mlambol@phru.co.za.
¹¹ Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Post Office Box 114, Diepkloof, Johannesburg, South Africa. Electronic address: chettyd@phru.co.za.
¹² Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Post Office Box 114, Diepkloof, Johannesburg, South Africa. Electronic address: wajaz@phru.co.za.
¹³ Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Post Office Box 114, Diepkloof, Johannesburg, South Africa; Johns Hopkins University, School of Medicine, 1550 Orleans St, Baltimore, MD 21231, USA. Electronic address: martinson@phru.co.za.
¹⁴ Johns Hopkins University, School of Medicine, 1550 Orleans St, Baltimore, MD 21231, USA; Johns Hopkins Bloomberg School of Public Health, Department of International Health, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: jgolub@jhmi.edu.
¹⁵ Colorado State University, Department of Environmental and Radiological Health Sciences, 1681 Campus Delivery, Fort Collins, CO 80523, USA. Electronic address: jessica.elf@colostate.edu.

PMID: 40543725
DOI: 10.1016/j.cct.2025.107985

Abstract

Background: Human immunodeficiency virus (HIV) remains an important cause of morbidity and mortality in South Africa (SA) with a gradual shift from opportunistic illness to pulmonary and cardiovascular disease among people living with HIV (PLWH). This shift is exacerbated by increases in prevalence of tobacco smoking and also few resources to support smoking cessation. Evidence-based smoking cessation strategies are yet to be fully evaluated among PLWH in this setting.

Objective: This project will optimize a smoking cessation treatment package for PLWH that can be integrated into existing HIV care in SA. We will identify the most effective and/or combination of the interventions and evaluate their potential for implementation and cost-effectiveness.

Methods: A balanced 2⁴ full factorial clinical trial will randomise 660 PLWH who smoke tobacco into one of 16 combinations of four intervention components (behavioural counselling, peer counselling, varenicline, and combination nicotine replacement therapy). Participants will be recruited from four healthcare facilities in SA, receive 12 weeks of intervention and the primary outcome will be 7-day point prevalence tobacco abstinence from smoking at one year, measuring both exhaled breath carbon monoxide (CO) and urinary cotinine. A mixed methods approach will be used to evaluate implementation using the Reach, Effectiveness, Adoptions, Implementation, Maintenance framework. Cost, cost-effectiveness, and budget impact of each intervention combination will be evaluated.

Conclusion: Results will inform which intervention components, and in what combination, are most efficacious in supporting smoking abstinence among PLWH in SA and those that have the greatest potential for effectiveness when brought to scale.

Clinical trial registration number: South African National Clinical Trials Registry.

Trial no: DOH-27-062023-9076.

Clinicaltrials: gov ID: NCT05413122.

Keywords: Behavioural counselling; HIV; Nicotine replacement therapy; Peer counselling; Tobacco smoking cessation; Varenicline.

Associated data

ClinicalTrials.gov/NCT05413122