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Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe

Dineke Frentz1, David AMC Van de Vijver1, Ana B Abecasis2, Jan Albert34, Osamah Hamouda5, Louise B Jørgensen6, Claudia Kücherer5, Daniel Struck7, Jean-Claude Schmit78, Jurgen Vercauteren9, Birgitta Åsjö10, Claudia Balotta11, Danail Beshkov12, Ricardo J Camacho132, Bonaventura Clotet14, Suzie Coughlan15, Algirdas Griskevicius16, Zehava Grossman17, Andrzej Horban18, Tatjana Kolupajeva19, Klaus Korn20, Leondios G Kostrikis21, Kirsi Liitsola22, Marek Linka23, Claus Nielsen5, Dan Otelea24, Dimitrios Paraskevis25, Roger Paredes13, Mario Poljak26, Elisabeth Puchhammer-Stöckl27, Anders Sönnerborg284, Danica Stanekova29, Maja Stanojevic30, Eric Van Wijngaerden31, Annemarie MJ Wensing32, Charles AB Boucher1* and on behalf of the SPREAD Programme

Author Affiliations

1 Erasmus Medical Center, Rotterdam, the Netherlands

2 Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal

3 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

4 Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden

5 Robert Koch Institute, Berlin, Germany

6 Statens Serum Institute, Copenhagen, Denmark

7 Laboratory of Retrovirology, CRP-Santé, Luxembourg, Luxembourg

8 Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg

9 Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium

10 Section for Microbiology and Immunology, The Gade Institute, University of Bergen, Bergen, Norway

11 University of Milan, Milan, Italy

12 Department of Virology, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria

13 Hospital Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal

14 irsiCaixa AIDS Research Institute & Lluita contra la SIDA Foundation, Hospital Universitari “Germans Trias i Pujol”, Badalona, Spain

15 University College Dublin, Dublin, Ireland

16 National Public Health Surveillance Laboratory, Vilnius, Lithuania

17 Sheba Medical Center, Tel Hashomer, Israel

18 Warsaw Medical University and Hospital of Infectious Diseases, Warsaw, Poland

19 Infectology Center of Latvia, Riga, Latvia

20 University of Erlangen-Nuremberg, Erlangen, Germany

21 University of Cyprus, Nicosia, Cyprus

22 National Institute for Health and Welfare, Helsinki, Finland

23 National Institute of Public Health, Prague, Czech Republic

24 Molecular Diagnostics, “Prof. Dr. Matei Bals” Institute for Infectious Diseases, Bucharest, Romania

25 Medical School, University of Athens, Athens, Greece

26 University of Ljubljana, Ljubljana, Slovenia

27 Medical University Vienna, Vienna, Austria

28 Divisions of Infectious Diseases and Clinical Virology, Karolinska Institute, Stockholm, Sweden

29 Slovak Medical University, Bratislava, Slovakia

30 University of Belgrade School of Medicine, Belgrade, Serbia

31 Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium

32 Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands

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BMC Infectious Diseases 2014, 14:407  doi:10.1186/1471-2334-14-407

Published: 21 July 2014



One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.


Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy.


The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM.


During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring.

Europe; HIV-1; Resistance; Transmission