The spread of HIV in sub-Saharan Africa continues largely unabated. To improve prevention interventions, a better understanding of the determinants of HIV infection is required. Conceptual frameworks can guide epidemiological investigation and prevent a misguided focus on single risk factors in isolation. Existing frameworks of HIV infection focus on transmission. However, the transmitting individual is rarely known. By contrast, data on individual HIV acquisition are available from longitudinal studies and tests for recent HIV infection. From the perspective of individuals susceptible to HIV, it is important to distinguish between factors determining the individual’s biological disposition and sexual behavior and community-level factors, which can affect both HIV acquisition and the likelihood that a sex partner chosen from a community will be infected with HIV and transmit the infection. We propose a framework that takes the susceptible individual as a starting point and links distal, proximate and biological determinants of HIV infection at both the individual and the community level. We describe three necessary ingredients for the use of the framework (identification of the relevant community, multilevel analysis and methods for causal inference).