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In most countries, the burden of HIV among people who inject drugs, men who have sex with men, and sex workers is disproportionately high compared with that in the general population. Meanwhile, coverage rates of effective interventions among those key populations (KPs) are extremely low, despite a strong evidence base about the effectiveness of currently available interventions. In its first decade, President's Emergency Plan for AIDS Relief (PEPFAR) is making progress in responding to HIV/AIDS, its risk factors, and the needs of KPs. Recent surveillance, surveys, and size estimation activities are helping PEPFAR country programs better estimate the HIV disease burden, understand risk behavior trends, and determine coverage and resources required for appropriate scale-up of services for KPs. To expand country planning of programs to further reduce HIV burden and increase coverage among KPs, PEPFAR has developed a strategy consisting of technical documents on the prevention of HIV among people who inject drugs (July 2010) and prevention of HIV among men who have sex with men (May 2011), linked with regional meetings and assistance visits to guide the adoption and scale-up of comprehensive packages of evidence-based prevention services for KPs. The implementation and scaling up of available and targeted interventions adapted for KPs are important steps in gaining better control over the spread and impact of HIV/AIDS among these populations.

Civil society has been part of the HIV/AIDS response from the very beginning of the epidemic, often becoming engaged before national governments. Traditional roles of civil society--advocacy, activism, serving as government watchdog, and acting as community caretaker--have been critical to the response. In addition, civil society organizations (CSOs) play an integral part in providing world-class HIV prevention and treatment services and helping to ensure continuity of care. The President's Emergency Program for AIDS Relief (PEPFAR) has significantly increased the global scale-up of combination antiretroviral therapy reaching for more than 5 million people in developing countries, as well as implementation of effective evidence-based combination prevention approaches. PEPFAR databases in 5 countries and annual reports from a centrally managed initiative were mined and analyzed to determine the numbers and types of CSOs funded by PEPFAR over a 5-year period (2006-2011). Data are also presented from Uganda showing the overall resource growth in CSO working for HIV. Case studies document the evolution of 3 indigenous CSOs that increased the capacity to implement activities with PEPFAR funding. A legacy of PEPFAR has been the growth of civil society to address social and health issues as well as recognition by governments that partnerships with beneficiaries and civil society result in better outcomes. Scale-up of the global response could not have happened without the involvement of civil society and people living with HIV. This game changing partnership to jointly tackle the problems that countries face may well be the greatest benefit emerging from the HIV epidemic.