The HIV Prevention Trials Network (HPTN) is conducting the HPTN 071 (PopART) study in 21 communities in Zambia and South Africa with support from a consortium of funders. HPTN 071 (PopART) is a community-randomized trial of a combination prevention strategy to reduce HIV incidence in the context of the generalized epidemic of southern Africa. The full PopART intervention strategy is anchored in home-based HIV testing and facilitated linkage of HIV-infected persons to care through community health workers and universal antiretroviral therapy for seropositive persons regardless of CD4+ cell count or HIV viral load. To further reduce the risk of HIV acquisition among uninfected individuals, the study aims to expand voluntary medical male circumcision, diagnosis and treatment of sexually transmitted infections, behavioral counseling, and condom distribution. The full PopART intervention strategy also incorporates promotion of other interventions designed to reduce HIV and tuberculosis transmission, including optimization of the prevention of mother-to-child HIV transmission and enhanced individual and public health tuberculosis services. Success for the PopART strategy depends on the ability to increase coverage for the study interventions whose uptake is a necessary antecedent to a prevention effect. Processes will be measured to assess the degree of penetration of the interventions into the communities. A randomly sampled population cohort from each community will be used to measure the impact of the PopART strategy on HIV incidence over 3 years. We describe the strategy being tested and progress to date in the HPTN 071 (PopART) study.