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A decade after the world’s leaders committed to fight the global HIV epidemic, UNAIDS notes progress in halting the spread of the virus. Access to treatment has in particular increased, with noticeable beneficial effects on HIV-related mortality. Further scaling-up treatment requires substantial human and financial resources and the continued investments that are required may further erode the limited resources for HIV prevention. Treatment can play a role in reducing the transmission of HIV, but treatment alone is not enough and cost-effective behavioural prevention approaches are available that in recent years have received less priority. HIV prevention may in the future benefit from novel biomedical approaches that are in development, including those that capitalize on the use of treatment. To date, evidence of effectiveness of biomedical prevention in real-life conditions is limited and, while they can increase prevention options, many biomedical prevention approaches will continue to rely on the behaviours of individuals and communities. These behaviors are shaped and constrained by the social, cultural, political and economic contexts that affect the vulnerability of individuals and communities. At the start of the 4th decade of the epidemic, it is timely to re-focus on strengthening the theory and practice of behavioural prevention of HIV.