Introduction: The search is on to find a cure for HIV/AIDS, but for the time being the adage ‘prevention is better than cure’ could not be more relevant to the HIV/AIDS context. Recently, attention to social and behavioral risk factors gave researchers the opportunity to explore new ways of developing interventions. Objectives: In an attempt to further explore these risk factors this study is comparing the difference in prevalence between the genders, and assessing the HIV-related knowledge, attitudes, and behavior in two populations; Zimbabwe, an African country with high HIV prevalence, and Senegal, an African country with low HIV prevalence. Method: The 2010-2011 Senegal DHS and the 2010-2011 Zimbabwe DHS were used secondary data for this study. They were both nationally representative datasets. Sample sizes of study population were 16,271from Zimbabwe and 20,102 from Senegal. IBM SPSS 22 was used to run chi-square tests for descriptive results of all independent and dependent variables, and binary logistic regression for associations between HIV-related knowledge, attitudes, and behavior and HIV status, as well as the women’s status and HIV status, and associations between these factors. Results: The results showed that n both countries, HIV infection had significantly positive associations with having more than one sex partners (Zimbabwe OR 1.117, Senegal OR 2.779). Moreover, the variables of women’s status varied between Zimbabwe and Senegal. HIV status in Zimbabwe was negatively associated with women's participation in decision-making about their own health, while it associated with this variable positively in Senegal (Zimbabwe OR 0.651, Senegal OR 1.969). Conclusion: Having more than one sexual partner were important indicators for HIV infection in both countries. Women in Zimbabwe seem to be more powerful than women in Senegal. Continued intervention research is warranted as there are clear patterns of risk between Zimbabwe and Senegal that highlight opportunities for more tailored prevention efforts surrounding gender roles, HIV knowledge, attitudes, and sexual risk-taking behavior.