BACKGROUND: Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. METHODS: Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. RESULTS: The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. CONCLUSIONS: Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.

AP HP Groupe hospitalier Bichat Claude Bernard IAME INSERM UMR 1137 Université Paris Diderot Sorbonne Paris Cité Paris France

Complejo Hospitalario Universitario de Granada Instituto de Investigación IBS Granada; on behalf of Cohorte de Adultos de la Red de Investigación en SIDA Spain

Department of Infectious Diseases National Institute for Health and Welfare Helsinki Finland

Department of Virology University Medical Center Utrecht The Netherlands

Erasmus MC University Medical Center Rotterdam The Netherlands

Faculty of Medicine Slovenian HIV AIDS Reference Centre University of Ljubljana Slovenia

Faculty of Medicine University of Belgrade Serbia

Hospital of Infectious Diseases Warsaw Poland

Infectiology Center of Latvia Riga

IrsiCaixa Foundation Badalona Spain

Karolinska Institute Solna

Karolinska University Hospital Stockholm Sweden

Lithuanian AIDS Center Vilnius Lithuania

Luxembourg Institute of Health Luxembourg

LuxembourgInstitute of Health Luxembourg

Medical University Vienna Austria

National Center of Infectious and Parasitic Diseases Sofia Bulgaria

National HIV Reference Laboratory Chaim Sheba Medical Center Tel Hashomer Israel

National Institute for Infectious Diseases Prof dr Matei Bals Bucharest Romania

National Reference Laboratory for HIV AIDS National Institute of Public Health Prague Czech Republic

National Retrovirus Reference Center University of Athens Greece

Rega Institute for Medical Research KU Leuven Belgium

Robert Koch Institute Berlin Germany

Slovak Medical University Bratislava Slovakia

St Elisabeth Hospital Tilburg The Netherlands

Statens Serum Institut Copenhagen Denmark

University College Dublin Ireland

University Hospital for Infectious Diseases Dr Fran Mihaljevic Zagreb Croatia

University of Bergen Norway

University of Cyprus Nicosia

University of Siena Italy

Zobrazit více v PubMed

Little SJ, Holte S, Routy JP et al. . Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med 2002; 347:385–94. PubMed

Violin M, Cozzi-Lepri A, Velleca R et al. . Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy. AIDS 2004; 18:227–35. PubMed

Kuritzkes DR, Lalama CM, Ribaudo HJ et al. . Preexisting resistance to nonnucleoside reverse-transcriptase inhibitors predicts virologic failure of an efavirenz-based regimen in treatment-naive HIV-1-infected subjects. J Infect Dis 2008; 197:867–70. PubMed

Wittkop L, Gunthard HF, de Wolf F et al. . Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study. Lancet Infect Dis 2011; 11:363–71. PubMed

European AIDS Clinical Society. EACS guidelines version 8.0. Available at: http://www.eacsociety.org/files/guidelines_8_0-english_web.pdf. Accessed 29 Octobre 2015.

Gunthard HF, Aberg JA, Eron JJ et al. . Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society–USA Panel. JAMA 2014; 312:410–25. PubMed

Wensing AM, Calvez V, Gunthard HF et al. . 2014 Update of the drug resistance mutations in HIV-1. Top Antivir Med 2014; 22:642–50. PubMed PMC

Bennett DE, Camacho RJ, Otelea D et al. . Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS One 2009; 4:e4724. PubMed PMC

Wensing AM, van de Vijver DA, Angarano G et al. . Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical management. J Infect Dis 2005; 192:958–66. PubMed

Wensing AM, Vercauteren J, van de Vijver D et al. . Transmission of drug-resistant HIV-1 in Europe remains limited to single classes. AIDS 2008; 22:625–35. PubMed

Vercauteren J, Wensing AM, van de Vijver DA et al. . Transmission of drug-resistant HIV-1 is stabilizing in Europe. J Infect Dis 2009; 200:1503–8. PubMed

Frentz D, Van de Vijver DA, Abecasis AB et al. . Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. BMC Infect Dis 2014; 14:407. PubMed PMC

Frentz D, van de Vijver D, Abecasis A et al. . Patterns of transmitted HIV drug resistance in Europe vary by risk group. PLoS One 2014; 9:e94495. PubMed PMC

Struck D, Lawyer G, Ternes AM, Schmit JC, Perez Bercoff D. COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification. Nucleic Acids Res 2014; 42:e144. PubMed PMC

Tang MW, Liu TF, Shafer RW. The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology 2012; 55:98–101. PubMed PMC

European Centre for Disease Prevention and Control/ WHO Regional Office for Europe. HIV/AIDS surveillance in Europe 2010. Available at: http://ecdc.europa.eu/en/publications/Publications/20121130-Annual-HIV-Surveillance-Report.pdf. Accessed 17 September 2015.

Gupta RK, Jordan MR, Sultan BJ et al. . Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis. Lancet 2012; 380:1250–8. PubMed PMC

Little SJ, Frost SD, Wong JK et al. . Persistence of transmitted drug resistance among subjects with primary human immunodeficiency virus infection. J Virol 2008; 82:5510–8. PubMed PMC

Castor D, Low A, Evering T et al. . Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. J Acquir Immune Defic Syndr 2012; 61:1–8. PubMed PMC

Burchell AN, Bayoumi AM, Rourke SB et al. . Increase in transmitted HIV drug resistance among persons undergoing genotypic resistance testing in Ontario, Canada, 2002–09. J Antimicrob Chemother 2012; 67:2755–65. PubMed

Xu HT, Colby-Germinario SP, Asahchop EL et al. . Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. Antimicrob Agents Chemother 2013; 57:3100–9. PubMed PMC

Picchio GR, Rimsky LT, Van Eygen V, Haddad M, Napolitano LA, Vingerhoets J. Prevalence in the USA of rilpivirine resistance-associated mutations in clinical samples and effects on phenotypic susceptibility to rilpivirine and etravirine. Antivir Ther 2014; 19:819–23. PubMed

Molina JM, Cahn P, Grinsztejn B et al. . Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet 2011; 378:238–46. PubMed

Rimsky L, Van Eygen V, Hoogstoel A et al. . 96-week resistance analyses of rilpivirine in treatment-naive, HIV-1-infected adults from the ECHO and THRIVE phase III trials. Antivir Ther 2013; 18:967–77. PubMed

Cossarini F, Boeri E, Canducci F et al. . Integrase and fusion inhibitors transmitted drug resistance in naive patients with recent diagnosis of HIV-1 infection. J Acquir Immune Defic Syndr 2011; 56:e51–4. PubMed

Stekler JD, McKernan J, Milne R et al. . Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007–2013. Antivir Ther 2015; 20:77–80. PubMed PMC