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The HIV epidemic has had a widespread impact on global scientific and cultural discourses related to gender, sexuality, and identity. ‘Male sex workers’ have been identified as a ‘key population’ in the global HIV epidemic; however, there are methodological and conceptual challenges for defining inclusion and exclusion of transgender women within this group. To assess these potential implications, this study employs self-critique and reflection to grapple with the empiric and conceptual implications of shifting understandings of sexuality and gender within the externally re-created etic category of ‘MSM’ and ‘transgender women’ in epidemiologic HIV research. We conducted a sensitivity analysis of our previously published meta-analysis which aimed to identify the scope of peer-reviewed articles assessing HIV prevalence among male sex workers globally between 2004 and 2013. The inclusion of four studies previously excluded due to non-differentiation of cisgender male from transgender women participants (studies from Spain, Thailand, India, and Brazil: 421 total participants) increased the overall estimate of global HIV prevalence among ‘men’ who engage in sex work from 10.5% (95% CI 9.4–11.5%) to 10.8% (95% CI 9.8–11.8%). The combination of social science critique with empiric epidemiologic analysis represents a first step in defining and operationalising ‘reflexive epidemiology’. Grounded in the context of sex work and HIV prevention, this paper highlights the multiplicity of genders and sexualities across a range of social and cultural settings, limitations of existing categories (i.e. ‘MSM’, ‘transgender’), and their global implications for epidemiologic estimates of HIV prevalence. [ABSTRACT FROM AUTHOR]