Journal of Medical Virology 87:978–984 (2015) Limited Increase in Primary HIV-1C Drug Resistance Mutations in Treatment Naı ¨ve Individuals in Ethiopia Kahsay Huruy, 1,2 Melanie Maier, 1 * Andargachew Mulu, 1 and Uwe G. Liebert 1 1 Institute of Virology, Leipzig University, Leipzig, Germany 2 Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, University of Gondar, Gondar, Ethiopia Antiretroviral drug resistance is a major chal- lenge for management and control of HIV-1 infection worldwide and particularly in resource limited countries. The frequency of primary drug resistance mutations (DRMs) and of naturally occurring polymorphisms was determined in 83 antiretroviral treatment (ART) naı¨ve Ethiopian individuals infected with HIV-1, consecutively enrolled in 2010. In all individuals HIV-1C was found. The median (interquartile range) of CD4 þ T-cell count and viral load were 100 (49–201) cells/ml and 44,640 (12,553–134,664) copies/ml, respec- tively. Protease (PR) and reverse transcriptase (RT) genes of HIV-1 RNA were amplified and sequenced. The proportion of primary DRM to any drug class, using the World Health Organization mutation lists, was 7.2% (6/83), thus exceeding the WHO threshold limit of 5%. Three individuals (3.6%) had non- nucleoside reverse transcriptase inhibitor (NNRTI) mutations, two individuals (2.4%) had protease inhibitor mutations, and one (1.2%) had mutations associated with two drug classes (nucleoside reverse transcriptase inhibitor and NNRTI). In addition, the fre- quency of polymorphisms in the PR and RT genes was higher compared with previous studies in Ethiopian as well as worldwide isolates. Hence, genotypic drug resistance testing as part of routine management of indi- viduals seems reasonable even in resource limited countries prior to treatment in order to allow proper choice of ART. J. Med. Virol. 87:978–984, 2015. # 2015 Wiley Periodicals, Inc. KEY WORDS: ART; primary drug resistance; protease; reverse transcrip- tase; polymorphism INTRODUCTION Infection with human immunodeficiency virus type 1 (HIV-1) and acquired immunodeficiency syndrome (AIDS) remain a major world-wide health problem. In 2012 an estimated 35 million people were living with the virus. Like other sub-Saharan Africa countries, Ethiopia is heavily affected with approximately 760,000 individuals living with HIV/AIDS and an adult prevalence of 1.3% [UNAIDS, 2013]. The avail- ability of antiretroviral treatment (ART) has led to a significant decrease in mortality and morbidity rates of HIV-1 [UNAIDS, 2013]. According to the World Health Organization (WHO) report the number of individuals receiving ART in low- and middle-income nations increased approximately 32-fold from 2002 to 2012 [WHO, 2013]. However, antiretroviral drug resistance remains a major challenge for manage- ment and control of HIV-1 infection [Imaz et al., 2011]. The large-scale accessibility of ART regimens in resource-constrained settings also bears the risk of an unnoticed evolution of resistant variants in ART experienced patients and their subsequent transmis- sion [Deeks, 2008]. The awareness of primary DRM led to the recommendation for HIV-1 drug resistance testing as soon as HIV-1 infection is diagnosed [Hirsch et al., 2008]. Primary DRM has declined over time in Europe [Wittkop et al., 2011]. In contrast, in the United States and Africa, the frequency of Conflict of interest: None. Authors’ contribution: KH, MM, AM and UGL participated in the design, analysis, and interpretation of the study results. First draft was prepared by KH and MM; final version was prepared by UGL. All authors approved the final manuscript.  Correspondence to: Melanie Maier, Institute of Virology, Leipzig University, Leipzig, Germany. E-mail: maier@medizin.uni-leipzig.de Accepted 4 November 2014 DOI 10.1002/jmv.24110 Published online 3 February 2015 in Wiley Online Library (wileyonlinelibrary.com).  C 2015 WILEY PERIODICALS, INC.