This paper makes methodological and empirical contributions to the study of HIV in the context of Botswana, a country with high HIV prevalence. Comparable evidence is presented from India to put the Botswana results in perspective. The results point to the strong role played by affluence and education in increasing HIV knowledge, promoting safe sex and reducing HIV prevalence. The study presents African evidence on the role played by the empowerment of women in promoting safe sex practices such as condom use. The lack of significant association between HIV prevalence and safe sex practice points to the danger of HIV-infected individuals spreading the disease through multiple sex partners and unprotected sex. This danger is underlined by the finding that females with multiple sex partners are at higher risk of being infected with HIV. These results take on special policy significance in the context of Botswana, where the issue of multiple sex partners has not been adequately addressed in the programme to contain the spread of HIV.