Transmission networks of (resistant) HIV-1 among men having sex with men in the Netherlands
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1 Transmission networks of (resistant) HIV-1 among men having sex with men in the Netherlands Daniela Bezemer NCHIV The Royal Tropical Institute Amsterdam, 24 November 2009 Daniela Bezemer1, Ard van Sighem1, Vladimir V. Lukashov2, Lia van der Hoek2, Nicole Back2, Rob Schuurman3, Charles A.B. Boucher3,4, Eric C.J. Claas5, Maarten C. Boerlijst6, Roel A. Coutinho7,8, Frank de Wolf1,9 for the ATHENA observational cohort 1HIV Monitoring Foundation, Amsterdam, The Netherlands; 2Department of Medical Microbiology, Academic Medical Centre, Amsterdam, The Netherlands; 3Department of Virology, University Hospital Utrecht, The Netherlands ; 4Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands; 5Department of Medical Microbiology, Leiden University Medical Center, The Netherlands; 6Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, The Netherlands; 7Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands; 8Center for Infectious Disease Control, National Institute of Public Health and the Environment, Bilthoven, The Netherlands; 9Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom AIDS, 2009/10
2 HIV Polymerase gene (pol) Sequenced to check for resistant mutations in order to start adequate therapy We use the mutual similarities to study the underlying transmission networks 1. Time from infection to onwards transmission 2. Contribution of the treated population
3 Numbers in ATHENA ~ July ,951 HIV-1 infected persons 53% reported to be infected by MSM contact 30 % of all MSM have a subtype B sequence available 403 identified with an HIV-1 subtype B infection with a known date of infection in the period new infections
4 Clustering of new HIV infections 175 of 403 (43%) patients in 63 transmission clusters with a bootstrap value 99, coloured red Difference between closest sequences per patient in a cluster 0.9% (IQR ) 1.4 %
5 The distribution in time between the dates of infections of the most likely transmission pair for all patients in a significant cluster Median time difference between dates of infection 1.4 years (IQR )
6 Transmission of resistant HIV-1 strains among 403 new infections 24 (6%) resistant 2 (1%) MDR study contact networks in a tree of 4090 HIV-1 subtype B pol gene sequences of 2877 persons
7 Sub-epidemics of resistant strains to one drug class 23 persons in 4 clusters with per cluster the same mutations that give resistance to NRT inhibitors
8 Multi Drug Resistance New infections The 2 of 403 new infections with a multidrug resistant strain did not cluster with any other sequence in the database All patients infected with a MDR 22 MDR transmissions found (1%) two were together in a cluster both resistant to all three drug classes.
9 Conclusions 1. Transmission takes place both during and after primary infection 2. Most transmission of resistance to one drug class from the untreated population 3. MDR is till now only transmitted occasionally Earlier diagnosis and treatment! AIDS, 2009/10
10 Acknowledgements DB was supported by grant 7014 from AIDS Fund Netherlands. The authors thank Maus Sabelis for useful discussions, Maria Prins for helping in identifying new infections, Luuk Gras for statistical assistance, and Sally Ebeling for English revision. The ATHENA national observational cohort is a collaboration between 24 HIV treatment centres in the Netherlands: Treating physicians (*Site coordinating physicians) Academisch Medisch Centrum bij de Universiteit van Amsterdam - Amsterdam: Dr. J.M. Prins*, Drs. J.C. Bos, Dr. J.K.M. Eeftinck-Schattenkerk, Dr. S.E. Geerlings, Dr. M.H. Godfried, Prof. dr. J.M.A. Lange, Dr. J.T.M. van der Meer, Dr. F.J.B. Nellen, Drs. D.P. Olszyna, Dr. T. van der Poll, Prof. dr. P. Reiss, Drs. S.U.C. Sankatsing, Drs. R. Steingrover, Drs. M. van der Valk, Drs. J.N. Vermeulen, Drs. S.M.E. Vrouenraets, Dr. M. van Vugt, Dr. F.W.M.N. Wit. Academisch Ziekenhuis Maastricht - Maastricht: Dr. G. Schreij*, Dr. S. van der Geest, Dr. A. Oude Lashof, Dr. S. Lowe, Dr. A. Verbon. Catharina Ziekenhuis - Eindhoven: Dr. B. Bravenboer*, Drs. M.J.H. Pronk. Emma Kinderziekenhuis - AMC Amsterdam: Prof. dr. T.W. Kuijpers, Drs. D. Pajkrt, Dr. H.J. Scherpbier. Erasmus MC - Rotterdam: Dr. M.E. van der Ende*, Drs. H. Bax, Drs. M. van der Feltz, Dr. L.B.S. Gelinck, Drs. Mendoca de Melo (until September 1, 2008), Dr. J.L. Nouwen, Dr. B.J.A. Rijnders, Dr. E.D. de Ruiter, Dr. L. Slobbe, D rs. C.A.M. Schurink, Dr. T.E.M.S. de Vries. Erasmus MC - Sophia - Rotterdam: Dr. G. Driessen, Dr. M. van der Flier, Dr. N.G. Hartwig. Flevoziekenhuis - Almere: Dr. J. Branger. Haga Ziekenhuis, locatie Leyenburg - Den Haag: Dr. R.H. Kauffmann*, Drs. K. Pogány (until August 1, 2008), Dr. E.F. Schippers (from May 1, 2008). Isala Klinieken - Zwolle: Dr. P.H.P. Groeneveld*, Dr. M.A. Alleman. Kennemer Gasthuis - Haarlem: Prof. dr. R.W. ten Kate*, Dr. R. Soetekouw. Leids Universitair Medisch Centrum - Leiden: Dr. F.P. Kroon*, Dr. S.M. Arend, Drs. M.G.J. de Boer, Prof. dr. P.J. van den Broek, Prof. dr. J.T. van Dissel, Drs. C. van Nieuwkoop. Maasstadziekenhuis - locatie Clara - Rotterdam: Dr. J.G. den Hollander*. Medisch Centrum Alkmaar - Alkmaar: Dr. W. Bronsveld*. Medisch Centrum Haaglanden -locatie Westeinde - Den Haag: Dr. R. Vriesendorp*, Dr. F.J.F. Jeurissen, Dr. E.M.S. Leyten. Medisch Centrum Leeuwarden - Leeuwarden: Dr. D. van Houte*, Dr. M.B. Polée. Medisch Spectrum Twent e - Enschede: Dr. C.H.H. ten Napel*, Dr. G.J. Kootstra. Onze Lieve Vrouwe Gasthuis - Amsterdam: Prof. dr. K. Brinkman*, Drs. G.E.L. van den Berk, Dr. W.L. Blok, Dr. P.H.J. Frissen, Drs. W.E.M. Schouten.St. Medisch Centrum Jan van Goyen - Amsterdam: Dr. A. van Eeden*, Dr. D.W.M. Verhagen. Slotervaart Ziekenhuis - Amsterdam: Dr. J.W. Mulder*, Dr. E.C.M. van Gorp, Dr. A.T.A. Mairuhu, Drs. R. Steingrover, Dr. J. Wagenaar. St. Elisabeth Ziekenhuis - Tilburg: Dr. J.R. Juttmann*, Dr. M.E.E. van Kasteren. St. Lucas Andreas Ziekenhuis - Amsterdam: Dr. J. Veenstra*, Dr. W.L.E. Vasmel. Universitair Medisch Centrum St. Radboud - Nijmegen: Dr. P.P. Koopmans*, Drs. A.M. Brouwer, Dr. A.S.M. Dofferhoff, Prof. dr. R. de Groot, Drs. H.J.M. ter Hofstede, Dr. M. Keuter, Dr. A.J.A.M. van der Ven. Universitair Medisch Centrum Groningen - Groningen: Dr. H.G. Sprenger*, Dr. S. van Assen, Dr. J.T.M. van Leeuwen, Dr. C.J. Stek. Universitair Medisch Centrum Groningen - Beatrix Kliniek - Groningen: Dr. R. Doedens, Dr. E.H. Scholvinck. Universitair Medisch Centrum Utrecht - Utrecht: Prof. dr. I.M. Hoepelman*, Dr. M.M.E. Schneider, Prof. dr. M.J.M. Bonten, Dr. P.M. Ellerbroek, Drs. C.A.J.J. Jaspers, Drs. L.J. Maarschalk-Ellerbroek, Dr. J.J. Oosterheert, Dr. E.J.G. Peters, Dr. T. Mudrikova, Drs. M.W.M. Wassenberg, Dr. S. Weijer. WilhelminaKinderziekenhuis - UMC Utrecht: Dr. S.P.M. Geelen, Dr. T.F.W. Wolfs. VU Medisch Centrum - Amsterdam: Prof. dr. S.A. Danner*, Dr. M.A. van Agtmael, Drs. W.F.W. Bierman, Drs. F.A.P. Claessen, Drs. M.E. Hillebrand, Drs. E.V. de Jong, Drs. W. Kortmann, Dr. R.M. Perenboom, Drs. E.A. bij de Vaate. Ziekenhuis Rijnstate - Arnhem: Dr. C. Richter*, Drs. J. van der Berg, Dr. E.H. Gisolf. Ziekenhuis Walcheren - Vlissingen: Dr. A.A. Tanis*. St. Elisabeth Hospitaal/Stichting Rode Kruis Bloedbank - Willemstad, Curaçao: Dr. A.J. Duits, Dr. K. Winkel. Virologists: Academisch Medisch Centrum bij de Universiteit van Amsterdam - Amsterdam:Dr. N.K.T. Back, Dr. M.E.G. Bakker, Dr. H.L. Zaaijer.Prof. dr. B. Berkhout, Dr. S. Jurriaans. CLB Stichting Sanquin Bloedvoorziening -Amsterdam: Dr. Th. Cuijpers.Onze Lieve Vrouwe Gasthuis - Amsterdam: Dr. P.J.G.M. Rietra, Dr. K.J. Roozendaal; Slotervaart Ziekenhuis - Amsterdam: Drs. W. Pauw, Drs. P.H.M. Smits, Dr. A.P. van Zanten.VU Medisch Centrum - Amsterdam: Dr. B.M.E. von Blomberg, Dr. A. Pettersson, Dr. P. Savelkoul; Ziekenhuis Rijnstate - Arnhem:Dr. C.M.A. Swanink; HAGA, ziekenhuis, locatie Leyenburg - Den Haag: Dr. P.F.H. Franck, Dr. A.S. Lampe; Medisch Centrum Haaglanden, locatie Westeinde - Den Haag: Drs. C.L. Jansen.; Streeklaboratorium Twente - Enschede: Dr. R. Hendriks.Streeklaboratorium Groningen - Groningen: Dr. C.A. Benne;.Streeklaboratorium Volksgezondheid Kennemerland - Haarlem: Dr. J. Schirm, Dr. D. Veenendaal.Laboratorium voor de Volksgezondheid in Friesland - Leeuwarden: Dr. H. Storm, Drs. J. Weel, Drs. J.H. van Zeijl; Leids Universitair Medisch Centrum - Leiden: Dr. H.C.J. Cla as, Prof. dr. A.C.M. Kroes.Academisch Ziekenhuis Maastricht - Maastricht: Prof. dr. C.A.M.V.A. Bruggeman, Drs. V.J. Goossens.Universitair Medisch Centrum St. Radboud - Nijmegen: Prof. dr. J.M.D. Galama, Dr. W.J.G. Melchers, Dr. Verduyn-Lunel.Erasmus MC - Rotterdam:Dr. G.J.J. van Doornum, Dr. H.G.M. Niesters, Prof. dr. A.D.M.E. Osterhaus, Dr. M. Schutten.St. Elisabeth Ziekenhuis - Tilburg: Dr. A.G.M. Buiting.Universitair Medisch Centrum Utrecht - Utrecht: Dr. C.A.B. Boucher, Dr. E. Boel, Dr. R. Schuurman.Catharina Ziekenhuis - Eindhoven: Dr. A.F. Jansz, drs. M. Wulf; Pharmacologists: Medisch Centrum Alkmaar - Alkmaar: Dr. A. Veldkamp.Slotervaart Ziekenhuis - Amsterdam: Prof. dr. J.H. Beijnen, Dr. A.D.R. Huitema.Universitair Medisch Centrum St. Radboud - Nijmegen: Dr. D.M.Burger.Academisch Medisch Centrum bij de Universiteit van Amsterdam - Amsterdam: Drs. H.J.M. van Kan.
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