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As understanding and integrating the structural and biomedical determinants of HIV infection is essential for the success of prevention efforts, there is a need for biomedical and social scientists to work together.A review of the biomedical research literature indicates that the two major routes of HIV transmission, sexual and injection drug use behaviours, are primarily understood as biological. A review of the social science literature, however, indicates that such a positioning provides a very weak basis for prevention, as these behaviours or practices are socially produced; that is, they are patterned by socio-cultural, economic and political forces as well as by biological factors. This paper compares successful with unsuccessful prevention interventions/programmes highlighting the central importance of the structural determinants of risk. For HIV-prevention programmes to be effective, the focus must shift from behaviour, for example, from vaginal intercourse, to the cultural forms in which it is enacted; that is, to marriage, concurrent partnering, sex work, and so forth.This paper concludes that multidisciplinary teams provide a good starting place for the development of effective prevention programmes.