The prevalence of HIV&AIDS is embedded in social and economic inequity and the relationship between social determinants and HIV incidence is well established. The aim of this study was to determine which socio-economic and demographic factors are related to HIV status in the age group 18 to 49 years in informal settlements in the Eastern Cape, South Africa. This cross-sectional study was conducted in 3 informal settlements (n = 752) during March 2013 within the Nelson Mandela Bay and Buffalo City districts. A proportional cluster sample was selected and stratified by area and formal plot/squatter households in open areas. Respondents who volunteered to participate had to provide informed written consent before trained, bilingual peer educators interviewed them and completed the structured questionnaire. HIV status was determined and information on demographic and socio-economic variables was included in the bivariate analysis. The prevalence of HIV was higher, at 17.3%, than the 2011 estimated national prevalence among the general population in South Africa. The level of education (Ï(2) = 5.50, df = 1, p < 0.05), geographical site (Ï(2) = 7.41, df = 2, p < 0.05), gender (Ï(2) = 33.10, df = 1, p < 0.0005), household food insecurity (Ï(2) = 4.77, df = 1, p < 0.05), cooking with cast iron pots (Ï(2) = 15.0, df = 3, p < 0.05) and availability of perceived 'wealth' indicators like mobile telephones and refrigerators (Ï(2) = 9.67, df = 2, p < 0.05) were significantly associated with HIV-status. No significant associations could be demonstrated between household income, the number of people living in the household and the availability of electricity/water and HIV status. As the observed levels of HIV prevalence underlined gender bias and failure to graduate from high school, future interventions should focus on HIV prevention in female schoolchildren. However, HIV infection is also prevalent among wealthier individuals in informal settlements, which indicates that renewed efforts should be made to improve sexual risk behaviour within this group.