Documented Prevalence of HIV Type 1 Antiretroviral Transmitted Drug Resistance in Ireland from 2004 to 2008 Cillian F. De Gascun, 1,2 Allison Waters, 1 Ciara Regan, 1 Jane O’Halloran, 3 Gillian Farrell, 4 Suzie Coughlan, 1 Colm Bergin, 4 William G. Powderly, 2 and William W. Hall 1,2 Abstract HIV-1-infected individuals with transmitted HIV drug resistance (TDR) begin antiretroviral therapy (ART) with a lower genetic barrier to resistance and a higher risk of both virological failure and of developing further resistance. TDR surveillance informs HIV-1 public health strategies and first line ART. TDR has not been studied nationally in an Irish population. This study includes all new HIV diagnoses from January 2004 to September 2008 from the National Virus Reference Laboratory, University College Dublin. HIV-1 protease and reverse transcriptase sequences were generated, and resistance mutations identified using the Siemens TRUGENE HIV-1 Genotyping System. Subtypes were determined using web-based genotyping tools. The study comprised 1579 patients. There were 305 new diagnoses in 2004 (173 male; 132 female), 298 in 2005 (175M; 123F), 321 in 2006 (197M; 124F), 297 in 2007 (184M; 113F), and 358 (235M; 123F) in 2008. HIV-1 RNA was sequenced from 158/305 patients in 2004, 199/298 in 2005, 225/321 in 2006, 203/297 in 2007, and 275/358 in 2008. The overall TDR rate was 6.3%, peaking in 2006 at 10.4% and declining to 5.3% in 2008. The majority of TDR was seen in Irish born individuals with HIV-1 subtype B infection. The TDR rate in Ireland is comparatively low. Thus, a health technology assessment is required to ascertain the most cost effective use of genotypic antiretroviral resistance testing (GART) in the future: the current approach of performing baseline GART on all new diagnoses, or perhaps a more targeted approach that focuses on patients commencing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Introduction H uman immunodeficiency virus type 1 (HIV-1) was introduced into humans during the first half of the twentieth century. 1 While there are now more than 25 anti- viral agents available for the treatment of HIV infection, and the prognosis for those infected—in the developed world at least—continues to improve, effective control of the HIV pandemic remains elusive. Although there are a number of reasons for this, one of the most significant is drug resistance, which may be primary (transmitted) or secondary (acquired). Transmitted (or primary) HIV drug resistance occurs when a virus already possessing resistance-associated mutations infects a drug-naive individual. Although both acquired and transmitted HIV-1 drug resistance (TDR) are public health concerns, it is the latter that has the potential to more signif- icantly impact the effectiveness of first-line antiretroviral therapy (ART) at the population level. Persons with TDR begin ART with a lower genetic barrier to resistance, a higher risk of virological failure, and a higher risk of developing further resistance, even to those drugs in their treatment regimen that were originally fully active. 2 Consequently, HIV drug resistance surveillance has been advocated and pro- grams funded by the WHO and the European Union estab- lished to support public health bodies in designing education and prevention programs, to minimize the development and transmission of drug-resistant viruses, and to support the rational use of ART by treatment programs, clinicians, and policy makers. Studies in Europe and North America have reported TDR prevalence of between 5% and 15% in newly diagnosed in- dividuals, and from 10% to 25% in acutely infected individ- uals. 2 For this reason, routine genotypic antiretroviral resistance testing (GART) is recommended for all newly 1 National Virus Reference Laboratory, University College Dublin, Dublin, Ireland. 2 School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. 3 Department of Infectious Diseases, Mater Misericordiae Hospital, Dublin, Ireland. 4 Department of Genito-Urinary Medicine and Infectious Diseases, St. James’ Hospital, Dublin, Ireland. AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 27, Number 00, 2011 ª Mary Ann Liebert, Inc. DOI: 10.1089/aid.2011.0166 1