The expanding reliance on the health sciences to address social problems is well documented, as are the effects of the social construction of public (health) problems on ‘target’ populations, intervention design and broader social systems. Less attention has been given in the literature to the cultural meanings that configure public health efforts themselves. This study demonstrates how the cultural understandings of sex and sexuality that inform US human immunodeficiency virus (HIV) prevention policy in sub-Saharan Africa shape policy recommendations. Based on an analysis of 119 US policy documents, a relatively stable and highly gendered narrative of sexual risk was found across the Clinton and (G.W.) Bush administrations. This narrative locates HIV risk in (what is constructed to be) the inevitable clash between women’s sexuality and men’s sexuality, and delineates HIV risk by the form of relationship in which sex occurs. The two narratives diverge at this point, offering different definitions of ‘bad’ sex and ‘good’ sex. This divergence helps to explain the different prevention foci of the administrations – condoms during the Clinton era and abstinence-outside-of-marriage during the Bush administration. In both cases, the sexual risk narrative points to individual targeted prevention strategies, even as the policy identifies structural factors as driving global HIV epidemics.