PROJECT SUMMARY/ABSTRACT Long-acting (LA) pre-exposure prophylaxis (PrEP) offers a promising alternative to existing HIV prevention methods. Research to assess end-user acceptability and actual experiences of novel delivery formulations has neglected, however, to include male perspectives, despite these products being appropriate for use by both men and women. This research aims to assess acceptability of and preferences for novel LA-PrEP delivery formulation use among key end users: heterosexual men and men who have sex with men (MSM) in South Africa. Early involvement of men in product development is an important opportunity to measure and address product acceptability and foster male ownership of novel strategies, thereby enhancing potential effectiveness and impact, and broadening male engagement in HIV prevention. LA-PrEP delivered by implant or injection addresses user preferences for simplicity, discretion, and longer dose duration. Currently, there are several PrEP implants in preclinical development and a few injectable formulations in early human phase trials. Biomedical strategies have two core components: the active pharmaceutical ingredient and the delivery mechanism; both of which contribute to acceptability and successful use of products. Research to assess acceptability of placebo use of LA-PrEP delivery forms among end users provides insight that may apply to the many products under development. The contraceptive field provides substantial information about potential acceptability and use of LA delivery methods among women in sub-Saharan Africa (SSA). However, there is a gap in knowledge regarding acceptability of implant and injectable dosing platforms among men, particularly in SSA. We propose a 4-year study to comparatively examine acceptability and preferences of placebo implants and injectables using a crossover-designed mixed methods study among heterosexual men and MSM in Johannesburg and Cape Town, South Africa. We hypothesize that men will find implant use acceptable as a delivery form and no less acceptable than intramuscular injections. First, we will do formative qualitative research with men (n=40) to assess knowledge and experiences and inform messages and materials for our Aim 2 and 3 work. Subsequently, we will conduct a clinical crossover in which men (n=200) will wear placebo implants for 6 months and have three bimonthly injections in a randomized sequence. Preferences for these delivery forms and product attributes of these LA methods, oral PrEP, and condoms will then be measured using a discrete choice experiment survey.