Transmission of resistant HIV-strains in patients with documented date of HIV-infection in the German HIV-1 Seroconverter Cohort ( ) A decade of observation Bartmeyer B, Kuecherer C, Werning J, Kollan C, Hamouda O Robert Koch-Institute, Berlin, Germany Deptartment of Infectious Disease Epidemiology

2 Objectives HIV-1-Seroconverter Study to determine factors influencing disease progression to analyse occurrence and spread of HIV-1 subtypes to investigate the transmission and the spread of drug resistant HIV-1 National prospective multi-centre open cohort study (1997) among persons with well defined dates of infection

3 Methods Documented Seroconverters last negative and first positive HIV-AB test ≤ 3 years date of infection: mid point between both tests Acute Seroconverters HIV RNA+, EIA– or EIA+ and indeterminate WB date of infection: first reactive test used as proxy HIV Seroconverter: HIV-infected patients with a known or well defined date of infection

4 Background Incidence / Prevalence of TDR Newly diagnosed Incident and prevalent infections Newly diagnosed HIV infections „Chronic“ HIV infections New („acute“) HIV infections Uninfected at risk Incident and prevalent infections not yet diagnosed

5 Background Incidence / Prevalence of TDR Newly diagnosed HIV infections Pre-existing („chronic“) HIV infections New („acute“) HIV infections Assessment of incidence of resistant HIV among newly infected individuals during a defined time intervall Analysis of time trends of TDR should be based on newly infected individuals Assessment of prevalence of resistant HIV among newly diagnosed individuals

6 Methods Genotypic resistance analysis pol-population sequences - Direct sequencing Identification of resistance mutations: - IAS-List 2007, Johnson et al Prediction of resistant phenotype - Stanford algorithm ( Version 4.3.1,Sep 2007) Level of resistance to each drug: sensitive: sensitive + potentially resistant intermediate: low + intermediate highly resistant resistant

7 Results Participants by year of SC and transmission group Year of seroconversion Patients n

8 Results Patient characteristics Study Population 1563 (12/2007) Sex92% men MSM82% IDU4% Heterosexuals11% HPC3% nonB subtype8%

9 Results Patient characteristics Genotyped (N)1043 (67%) ( ) Primary mutations143 (13.7%, CI ) Sex139 men (97%) 4 women (3%) Age33 (IQR, 18-61) CDC classification96% A 3% B 0,7% C CD4 cell count (cells/µl, median)428 cells/µl HIV RNA (copies/ml, median)10 5 copies/ml

10 Results TDR in HIV-1 seroconverters by year of SC Prevalence ( ) 13.7% ( )

11 Results Factors potentially associated with TDR

12 Results Resistance – Drug classes Drug classes percent % Genotyped: N=1043 Susceptible: 86.3% Resistant: 13.7%

13 Results Trends in TDR - predicted phenotype - Year of seroconversion Percent % PI: *p=0.007 NRTI: *p=0.02 NNRTI:p=0.18

14 Results Predominant resistance to single drug classes NRTI PI NNRTI 1 NRTI >1NRTI 1 PI >1PI 1 NNRTI >1NNRTI % mono resistant HIV 88% single class resistance (103/117) 53% caused by singletons (54/103) PI- and NNRTI-singletons >NRTI

15 Summary 1/7 new HIV infections in Germany is with resistant HIV Resistance to single drug classes predominant - mainly singleton resistance mutations (PI, NNRTI) Significant decrease of NRTI and PI resistance TDR was not influenced by exposure category, sex or age Continued monitoring of TDR is neccessary Where possible time trends in TDR should be observed among persons with well defined dates of infection

16 Funded by the German Ministry of Health Robert Koch-Institut Department Infectious Disease Epidemiology HIV/AIDS, STD Unit Johanna Werning Parvin Ghassim Christian Kollan Britta Klose Project HIV Variability and Molecular Epidemiology Dr. Claudia Kücherer Sabrina Neumann Kathrin Gube Hanno v. Spreckelsen

Aachen Augsburg Berlin Bielefeld Bochum Bonn Dortmund Dresden Duisburg Düsseldorf Frankfurt/M Frankfurt/O. Freudenstadt Halle/Saale Dres. Knechten, Habets Klinikum Augsburg Ärzteforum Seestraße Augusta-Viktoria Krankenhaus (Vivantes) Dres. Bienieck, Cordes Dr. Claus Dr. Dobao Dres. Dupke, Carganico Dr. Fenske Dres. Freiwald, Rausch Dres. Gölz, Moll, Schleehauf Dr. Hintsche Dres. Jessen Dres. Krauthausen, Köppe Dr. Reuter Dres. Schlote, Lauenroth-Mai, Schuler Dr. Schmidt Dr. Schüler-Maué Dres. Schranz, Fischer Krankenhaus Prenzlauer Berg Institut für Tropenmedizin Universitätsmedizin Berlin Charité Krankenhaus MARA II St. Joseph Hospital Universitätsklinik Bonn Klinikum Dortmund Städtisches Krankenhaus Dresden-Neus Dr. Becker-Boost Dr. Kwirant Universitätsklinik Düsseldorf Universitätsklinik Joh.-W.-Goethe-Universität Dr. Markus Landratsamt Freudenstadt Universitätsklinik M.-Luther-Universität Hamburg Hannover Karlsruhe Koblenz Köln Leipzig Magdeburg Mainz München Münster Norderstedt Nürnberg Osnabrück Regensburg Remscheid Rostock Stuttgart Ulm Viernheim Wiesbaden ifi Allg.Krankenhaus St. Georg Dres. Adam, Weitner, Schewe Dr. Fenske Dr. Gellermann Universitätsklinik Eppendorf Med. Hochschule Hannover Dres. Buch, Leugner Landratsamt Karlsruhe Krankenhaus Kemperhof Dr. Bihari Dr. Ferdinand Universitätsklinik Köln Universitätsklinik Leipzig Universitätsklinik Otto-v.-Guericke Universität Klinikum der Joh.-Gutenberg-Universität Dr. Malm Dres. Jäger, Jägel-Guedes Dr. Rieger Städtisches Krankenhaus München Schwabing Technische Universität München Universitätsklinik Münster Dr. Soldan Klinikum Nürnberg Städt. Klinik Natruper Holz Universitätsklinik Regensburg Dres. Steege, Walter Dr. Kreft Universitätsklinik Rostock Dres. Schnaitmann, Schaffert, Trein, Ißler Dres. Ulmer, Frietsch, Müller Justizvollzugsanstalt Stuttgart Universitätsklinik Ulm Dr. van Treek Dr. Starke Great Thanks to