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The scale of the human immunodeficiency virus (HIV)/AIDS epidemic has exceeded all expectations since its identification 20 years ago. Globally, an estimated 36 million people are currently living with HIV, and some 20 million people have already died, with the worst of the epidemic centred on sub-Saharan Africa. But just as the spread of HIV has been greater than predicted, so too has been its impact on social capital, population structure and economic growth. Responding to AIDS on a scale commensurate with the epidemic is a global imperative, and the tools for an effective response are known. Nothing less than a sustained social mobilization is necessary to combat one of the most serious crises facing human development.

SUMMARY We have entered a new era in HIV prevention whereby priorities have expanded from biomedical discovery to include implementation, effectiveness, and the effect of combination prevention at the population level. However, gaps in knowledge and implementation challenges remain. In this Review we analyse trends in the rapidly changing landscape of HIV prevention, and chart a new path for HIV prevention research that focuses on the implementation of effective and efficient combination prevention strategies to turn the tide on the HIV pandemic.

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Background Through major efforts to reduce costs and expand access to antiretroviral therapy worldwide, widespread delivery of effective treatment to people living with HIV/AIDS is now conceivable even in severely resource-constrained settings. However, the potential epidemiologic impact of treatment in the context of a broader strategy for HIV/AIDS control has not yet been examined. In this paper, we quantify the opportunities and potential risks of large-scale treatment roll-out. Methods and Findings We used an epidemiologic model of HIV/AIDS, calibrated to sub-Saharan Africa, to investigate a range of possible positive and negative health outcomes under alternative scenarios that reflect varying implementation of prevention and treatment. In baseline projections, reflecting “business as usual,” the numbers of new infections and AIDS deaths are expected to continue rising. In two scenarios representing treatment-centered strategies, with different assumptions about the impact of treatment on transmissibility and behavior, the change in the total number of new infections through 2020 ranges from a 10% increase to a 6% reduction, while the number of AIDS deaths through 2020 declines by 9% to 13%. A prevention-centered strategy provides greater reductions in incidence (36%) and mortality reductions similar to those of the treatment-centered scenarios by 2020, but more modest mortality benefits over the next 5 to 10 years. If treatment enhances prevention in a combined response, the expected benefits are substantial—29 million averted infections (55%) and 10 million averted deaths (27%) through the year 2020. However, if a narrow focus on treatment scale-up leads to reduced effectiveness of prevention efforts, the benefits of a combined response are considerably smaller—9 million averted infections (17%) and 6 million averted deaths (16%). Combining treatment with effective prevention efforts could reduce the resource needs for treatment dramatically in the long term. In the various scenarios the numbers of people being treated in 2020 ranges from 9.2 million in a treatment-only scenario with mixed effects, to 4.2 million in a combined response scenario with positive treatment–prevention synergies. Conclusions These analyses demonstrate the importance of integrating expanded care activities with prevention activities if there are to be long-term reductions in the number of new HIV infections and significant declines in AIDS mortality. Treatment can enable more effective prevention, and prevention makes treatment affordable. Sustained progress in the global fight against HIV/AIDS will be attained only through a comprehensive response.