SUPPLEMENT ARTICLE PEPFAR’s Evolving HIV Prevention Approaches for Key Populations—People Who Inject Drugs, Men Who Have Sex With Men, and Sex Workers: Progress, Challenges, and Opportunities Richard Needle, PhD, MPH,* Joe Fu, BS,* Chris Beyrer, MD, MPH,† Virginia Loo, PhD,‡ Abu S. Abdul-Quader,§ James A. McIntyre, MBChB, FRCOG,k Zhijun Li, MD,¶ Jessie K. K. Mbwambo, MD,# Mercy Muthui,** and Billy Pick, JD†† Abstract: 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 popula- tion. 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 inter- ventions. 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 appropri- ate 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 tech- nical 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. Key Words: PEPFAR, key populations, HIV prevention (J Acquir Immune Defic Syndr 2012;60:S145–S151) INTRODUCTION Substantial evidence indicates that high population coverage of combinations of structural, biological, and behavioral interventions—linked with a supportive social and political environment—can decrease HIV risk and vul- nerability among key populations (KPs) such as people who inject drugs (PWID), men who have sex with men (MSM), and sex workers (SWs). 1–3 Yet, coverage of core interventions for these KPs that have proven to have the greatest impact in preventing the further spread of HIV is limited in most low- income and middle-income countries—including countries receiving support from the President’s Emergency Plan for AIDS Relief (PEPFAR). 3–7 In this article, we review the progress made by PEPFAR since 2004 in implementing programs for KPs. Specifically, we examine epidemiological patterns, the avail- ability and use of surveillance, surveys, size estimation methods, and scientific findings to plan and implement evidence-based HIV prevention interventions for KPs. Also included in this review are PEPFAR-specific and illustrative case studies, which reflect best program practices for each of the KPs. We also examine the challenges ahead for PEP- FAR’s programming and make recommendations for KPs to ensure that efforts to introduce and scale-up evidence-based combination intervention packages for PWID, MSM, and SWs are implemented in all affected countries. Progress and Challenges in Implementing Surveillance, Surveys, and Size Estimation Activities for KPs During PEPFAR’s early years, limited data on hard- to-reach, hidden, and stigmatized populations made it difficult to target resources and plan and implement programs to From the *Office of the US Global AIDS Coordinator, Department of State, Washington, DC; †Center for Public Health and Human Rights, Johns Hopkins Center for AIDS Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; ‡Partnership for Epidemiological Anal- ysis, Honolulu, HI; §Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, GA; kAnova Health Institute, Johannes- burg, South Africa and School of Public Health and family medicine, university of Cape Town, Cape Town, South Africa; ¶Division of Global HIV/AIDS, US CDC Global AIDS Program, China Office, China; #Department of Psychiatry and Mental Health, Muhimbili National Hospital, Dar es Salaam, Tanzanial; **Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Kenya; and ††US Agency for International Development. Various authors have professional relationships with PEPFAR (either as employees of PEPFAR-supported US Government agencies or as grantees/ contractors) as outlined in the Copyright Transfer Agreement forms. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, the US Government, or the World Health Organization. CB serves on the PEPFAR Scientific Advisory Board (unpaid). The authors have no other funding or conflicts of interest to disclose. Correspondence to: Richard Needle, PhD, MD, Office of the Global AIDS Coordinator, SA-29, 2nd floor 2201 C. Street NW, Washington, DC 20522–2920. Copyright © 2012 by Lippincott Williams & Wilkins J Acquir Immune Defic Syndr  Volume 60, Supplement 3, August 15, 2012 www.jaids.com | S145