Implementing oral (event-driven and daily) and long-acting pre-exposure prophylaxis in mobile men in Sub-Saharan Africa: a phase 3b, open-label, hybrid type 2 implementation and effectiveness trial (MOBILE MEN)

Abstract Background: Men who are mobile for work are a key population at high risk of acquiring HIV. Flexible pre-exposure prophylaxis (PrEP) options, including event-driven (ED) oral PrEP and long-acting injectable cabotegravir (CAB-LA), may offer increased access and acceptability for these men. However, limited data exist on the effectiveness and implementation of CAB-LA and ED PrEP among mobile men in Africa. Our study aims to assess the effectiveness and implementation of CAB-LA and oral Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (both daily and ED) through comparison of uptake, retention in care, coital coverage, and participant choice. Methods: We will conduct a mixed method, phase 3b, open-label, hybrid type 2 implementation and effectiveness randomized controlled trial (RCT). The trial will be carried out in 400 HIV negative men aged 18 years or older in South Africa and Uganda. Men will be randomized 1:1 to either Group A: oral TDF/FTC PrEP (ED or daily) or Group B: CAB-LA over 9-months. After 9 months, participants from both groups will be offered a choice of PrEP (oral TDF/FTC or CAB-LA) for a further 9 months, with the ability to change their choice as required. Various strategies to support PrEP adoption, initiation, and persistence will be implemented, monitored, and reported on using a RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) implementation science framework. Discussion: This study will provide critical data to inform scalable delivery models for both oral and injectable PrEP among mobile men at high risk for HIV acquisition. Findings will also highlight the potential of PrEP choice delivery and its benefits, offering evidence for governments to consider in the roll out of injectable PrEP in public health systems. Trial registration: NCT06133686, registered 14 November 2023. PACTR202409632006463, registered on 2 September 2024