The sociopolitical impact and consequent scale and scope of the human immunodeficiency virus (HIV) treatment program are unprecedented in the history of infectious diseases. Internationally coordinated efforts, such as the “3 by 5” initiative, as well as the updated global target of providing antiretroviral therapy (ART) to 15 million people by the end of 2015, resulted in ART becoming accessible, not only in unparalleled volumes, but also in previously inconceivable locations. Globally, the number of people receiving ART has tripled over the last 5 years and, of the estimated 10.6 million people on treatment at the end on 2012, 9.7 million were in lowand middle-income countries (LMICs). This number is expected to increase sharply, given that a total of 26 million people in LMICs are now eligible for ART under the 2013 World Health Organization (WHO) Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection. The exponential expansion of treatment programs has averted an estimated 6.6 million AIDS-related deaths between 1995 and 2012, including 5.5 million deaths in LMICs [1]. Despite the undisputed benefits of ART in terms of reduced HIV-related morbidity and mortality, the long-term success of the treatment program is threatened by the emergence and spread of drug-resistant HIV. The development of HIV drug resistance (HIVDR) has significant public health implications, such as limiting the response to ART, restricting future treatment options, increasing treatment costs, and creating a reservoir for transmission of resistant virus to newly infected individuals [2]. National health systems in many LMICs are plagued by unique treatment and program deficiencies that may facilitate the development of HIVDR, such as the use of low-cost, less-tolerable (eg, stavudine), and substandard regimens (eg, singledose nevirapine for prevention of motherto-child HIV transmission); limited access to HIV RNA monitoring; drug stockouts; suboptimal systems to support long-term adherence; and frequent drug– drug interactions due to the unavailability of newer medications (eg, unavailability of rifabutin necessitates the use of rifampicin together with nevirapine or lopinavir in patients coinfected with tuberculosis) [3–7]. Given the limited number of ART regimens available in resourceconstrained settings, the emergence of high-level HIVDR can devastate the goal of long-term treatment success. Acknowledging and responding to the threat of HIVDR, the WHO and the US Centers for Disease Control and Prevention (CDC), in collaboration with HIVResNet, an advisory body of international laboratories, clinicians, epidemiologists, and other HIVDR experts from >50 institutions, developed a global drug resistance surveillance strategy. As individual HIVDR testing is neither recommended nor feasible in most LMICs, this is a public health strategy, based on standardized, minimum-resource, routine population-level laboratory-based surveillance of HIVDR and assessments of ART program and clinic function. The strategy consists of 3 main assessment elements: (1) early warning indicators (EWI) of HIVDR; (2) surveys of acquired and transmitted HIVDR; and (3) surveys of HIVDR in children <18 months of age. EWIs are quality-of-care Received 17 February 2014; accepted 18 February 2014; electronically published 27 February 2014. Correspondence: T. M. Rossouw, MBChB, MPH, PhD, Faculty of Health Sciences, University of Pretoria, HW Snyman Bldg South 2-17, Bophelo Road, Prinshof, 0084 (OR), University of Pretoria, PO Box 667, Pretoria 0001, South Africa (theresa. rossouw@up.ac.za). Clinical Infectious Diseases 2014;58(11):1615–7 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/ciu114