The President's Emergency Plan for AIDS Relief (PEPFAR), announced January 2003, aims to provide 2 million people with anti-retroviral (ARV) treatment in 14 of the world's most severely affected countries. In May 2003 legislation established the position of the U.S. Global AIDS Coordinator in the State Department. GAO was asked to (1) identify major challenges to U.S. efforts to expand ARV treatment in resource-poor settings and (2) assess the Global AIDS Coordinator's response to these challenges. GAO interviewed 28 field staff from the U.S. Agency for International Development (USAID) and the Department of Health and Human Services (HHS), who most frequently cited the following five challenges to implementing and expanding ARV treatment in resource-poor settings: (1) coordination difficulties among both U.S. and non-U.S. entities; (2) U.S. government policy constraints; (3) shortages of qualified host country health workers; (4) host government constraints; and (5) weak infrastructure, including data collection and reporting systems and drug supply systems.