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

BACKGROUND HIV prevention pre-exposure prophylaxis (PrEP) has not been evaluated in men who mainly have sex with women and who may be at high risk of HIV acquisition due to high HIV prevalence in partners or particularly risky behaviours. Research to fill these data gaps is required to facilitate their inclusion in PrEP guidelines. Furthermore, with increasing PrEP options, recommendations to users and providers in high-burden / resource constrained settings is a key focus of the Sustainable Development Goal target to end AIDS by 2030. To date, HIV prevention research has largely focussed on adolescent girls and young women (AGYW) in low and middle income countries and men who have sex with men (MSM) in high income countries. Research on the user experience and choice of oral PrEP or CAB-LA PrEP amongst vulnerable heterosexual men is required.

Men consistently fare worse than women in levels of HIV testing and ART initiation with significant challenges in sub-Saharan Africa (SSA) for engagement and persistence in HIV treatment programmes well described. Despite this, heterosexual men represent the largest unaddressed gap in HIV services in SSA. Indeed, the failure of Treatment As Prevention trials (TASP) to show effect was in the main due to the failure to test and treat young men. Men who are mobile for work or through looking for work, are viewed by the WHO as a key population at high risk for HIV. As Africa's large youth bulge moves into young adulthood, the search for work and consequent mobile lifestyles will further increase.

In order to improve uptake, persistence, and effective use of all forms of PrEP, there is a need for simplified and differentiated delivery of PrEP that is person- and community-centred specifically for men. Effective use requires that all sex acts are covered by an effective prevention intervention such as PrEP. Given the importance of flexibility due to travel in this group, our hypothesis is that both oral PrEP (in particular, event-driven) and CAB-LA PrEP will be highly acceptable to men in two high-burden, resource limited, African countries, with high levels of effective use including persistence and coital coverage.

This is the first multi-country PrEP study for implementing both event-driven oral PrEP and Long-acting injectable cabotegravir (CAB-LA) in men in SSA (South Africa and Uganda). The programme will provide the evidence and cost-effectiveness analysis which is critical to decision making by African governments and donors on how to prioritise prevention resources and inform guidelines.

STUDY OBJECTIVES Effective use is defined as PrEP uptake and persistence, retention in care, and HIV exposure coverage with adequate drug tissue levels.