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Abstract: This paper is about expectations of oral PrEP, ‘a pill a day’ HIV pre-exposure prophylaxis that could be the first systemic form of HIV prevention for sexual or needle stick exposures. If found safe and effective—a difficult criteria to establish and, as such, is central to this paper—PrEP has the potential to significantly alter HIV prevention, well ahead of a vaccine or topical microbicide. Hence, despite uncertainty about PrEP''s viability, the potential significance of its impact on the HIV field requires early planning. In order to address this potentiality, we use a methodological approach drawn from the sociology of expectations to examine interviews with United States-based scientific stakeholders in the trialing of PrEP. We identify how PrEP is anticipated as both stable object and process involving multiple contingencies. These divergent conceptions enable us to illuminate a range of social, cultural, ethical, pharmaceutical and medical possibilities understood to potentially arise with PrEP. Further, they lead us to propose that the multiple contingencies that enact PrEP as an emergent entity offer scope for rethinking PrEP and, more broadly, the challenges of HIV prevention. [Copyright &y& Elsevier]