Frank de Wolf HIV Monitoring Foundation Amsterdam, The Netherlands

Transcriptie

1 Scaling up testing and counselling as it looks from treatment data monitoring perspectives: The applied research outcomes and the policy implications it generates Dutch experience Frank de Wolf HIV Monitoring Foundation Amsterdam, The Netherlands

2 Outline HIV Monitoring Foundation & HIV counselling and testing HIV/AIDS in the Netherlands Antiretroviral treatment Impact on the epidemic Impact of time between infection and HIV diagnosis

3 HMF and T&C HMF is involved in HIV care, collects data from patients followed in one of the 24 HIV treatment centres in the country and monitors changes in the course of infection and the epidemic Data Data Data New Infections New Diagnosed cases New AIDS cases Death Testing and counselling: HIV treatment centres (counselling: specifically trained nurses) STD out-patient facilities (municipal health services; counselling: specifically trained nurses; anonymous testing available) General practitioners (primary care physicians)

4 HIV and AIDS current situation in the Netherlands Less AIDS Less Death More Infections

5 Less AIDS and death Highly active antiretroviral therapy (HAART) was introduced in 1996 as standard of care for the treatment of HIV Before HAART, HIV was treated with on or a combination of two anti-hiv drugs, with a limited effect. After introduction of HAART, the number of AIDS diagnoses and HIV death declined Deaths AIDS cases De Boer et al., RIVM 26 Sources AIDS: AIDS registration Health Inspectorate <2, HMF 2. Sources deaths: CBS <22, HMF

6 Ten years HAART in the Netherlands 1. How many are infected? 2. How many infected are registered? 3. How many got AIDS? 4. How many died? 5. How many are treated? 6. And not treated? 7. What s the effect of HAART on the epidemic?

7 How many are infected? 25 estimate: Op de Coul & Van Sighem, (1.-28.)

8 18.5 HIV infected persons.25% Prevalence (%) adults.2%.15%.1%.5%.% Op de Coul & Van Sighem HIV prevalence amongst adults (age 15-49):.23% Amongst MSM: 5.3% Amongst iv drug users: 5.3% Amongst CSW: 2.7%

9 How many HIV positives are registered? Number HIV+: Op de Coul & Van Sighem, 26 As per mid 26: Gras et al, (1.-28.) 12.59

10 1259 patients are registered 12 In new HIV diagnoses 1 8 In total 9254 men and 2699 women >13 years of age In addition: 16 boys and girls 13 years Percentage of men is increasing since 23 Main risk group: MSM N year of HIV diagnosis % year of diagnosis % male % female

11 How many got AIDS? Number HIV+: Op de Coul & Van Sighem, 26 N registered: Gras et al, 26 At or after HIV diagnose: Gras et al, (1.-28.)

12 3468 AIDS diagnoses c n 248 new AIDS diagnoses rd from 6 ei weeks after HIV diagnosispa 1598 after 1996 Average AIDS incidence: 2.9/1 e person-years In 1996: 9.6 and in 25: 2 Since 23 no major changes i 166 AIDS diagnoses after Sstart D HAART AIDS incidence after start HAART decreases sharply from 14.8 in 1996 to 2.6 in n o e s c r n e d pi Number of AIDS diagnoses in 25: 276 i 1 S e c n d i c n I A 2 After HIV diagnosis calendar year 2 After start of HAART calendar year

13 Time to death within 3 years of starting HAART according to CDC-C classification HR (95% CI) PML NHL DEM MAC HSV PNR KSA ISO Model adjusted for calendar year of starting HAART, CD4 cell count and HIV RNA at starting HAART, age, gender and transmission risk group. Hazard ratio s of the specific CDC-C diseases are relative to no CDC-event. TOX WAS ECA CMV TBC MYC CRS PCP CRC PML: Progressive multifocal leucoencephalopathy NHL:Non-Hodgkin lymphoma DEM: AIDS dementia complex MAC: Mycobacterium avium/kansasii HSV: Herpes simplex virus PNR: Recurrent pneumonia KSA:Kaposi s sarcoma ISO: Isosporidiasis TOX: Toxoplasmosis of the brain WAS: Wasting syndrome ECA: Oesophageal candidiasis CMV: Cytomegalovirus disease TBC:Tuberculosis MYC: Atypical Mycobacterium infection CRS: Cryptosporidiosis PCP: Pneumocystis carinii pneumonia CRC: Extrapulmonar Cryptococcosis

14 How many died? Number HIV+: Op de Coul & Van Sighem, 26 N registered: Gras et al, 26 AIDS: Gras et al, 26 Since 1996: Gras et al, (1.-28.)

15 985 deaths Av mortality ratio: 1.48 per 11 person-years Mortality in the total groupp does not change: 1.16 in 1996 y t and.84 in 26 Mortality is still higher as compared to the non-infected r o population, but comparable m to other chronic diseases In total 854 deaths after start of HAART Mortality declines after start of HAART from 4.4 in 1996 to 1.54 in 25. e y p - n y o t s i r l e a p t r o m r e i l a t 7 Mortality after HIV diagnosis calendar year 7 Mortality after start of HAART calendar year

16 Causes of death In 1996: 76% HIV related 1% non HIV related 14% unknown In 25: 39% HIV related 5% non HIV related 11% unknown p r o p o r t i o n 1% 8% 6% 4% 2% % non-hiv-related HIV-related unknown calendar year

17 Standardised Mortality Ratio SMR r : patient has r times higher probability of death than a non-infected individual SMR women CD4=2 CD4=35 CD4=6 SMR=1 NL diabetes UK diabetes men CD4=2 CD4=35 CD4=6 SMR=1 NL diabetes UK diabetes age [years] Source diabetes data: Baan et al., Epidemiology 24; Laing et al., Diabet Med age [years]

18 Predicted survival probability Predicted probability to reach a specific age for an asymptomatic male patient diagnosed at the age of 34. Probability to reach age of 7 72% non-infected 68% CD4 6 cells/mm 3 67% CD4 35 cells/mm 3 65% CD4 2 cells/mm 3 58% CD4 5 cells/mm 3 surival probability uninfected.4 HIV CD4 6 HIV CD HIV CD4 2 HIV CD age [years]

19 How many patients are (not) on HAART? Number HIV+: Op de Coul & Van Sighem, 26 N registered: Gras et al, 26 AIDS: Gras et al, 26 Deaths: Gras et al, (1.-28.) In 1996: 8292 Untreated: 2136 Gras et al, 26

20 8292 HAART treated: Virological effect After the first 24 weeks of HAART, the amount of HIV in blood has declined 3 logs 8% are below the detection threshold 388/534 naïve patients show viral rebounds after initial success Incidence of viral rebound is 3.2 per 1 person-years of follow-up log HIV-RNA copies/ml plasma a l l I Q R I Q R d i a g n o s i s start HAART 24 wks 48 wks

21 Immunological effect of HAART Patients continuously on HAART do show an increase of CD4 cells from median 221/mm 3 at start to 67/mm 3 after 7 years of treatment The highest increase is seen in the first 24 weeks and levels off thereafter The increase does not differ between baseline groups Difference from baseline (cells/mm3) Weeks from starting HAART < >5 In older patients and patients with viral rebounds after start of HAART the increase in CD4 cells is less.

22 f HIV resistance in t treated patients HAART failure decreased n in o ART experienced patients i Amongst naive patients cthe a percentage of HAART r failures increased slowlyf In 8% of the patients experiencing virological failure during treatment resistance is found s t n e i a p t pre-treated naïve kalenderjaar However: Resistance is measured in only 17% of the patients with virological failure during HAART

23 Transmission of resistant e g HIV t s i s e r a t n t e n c a r t e p s i s e r Since 21 resistance is found in 7.7% of the new HIV diagnoses In 14 patients high-level resistance In 6.% of the recent infections one or more mutations associated with resistance are found 3 patients with high-level resistance; 1 to all drug classes e g a t n e c r e p B A f o 25 r e newly diagnosed b 2 sm eu 15 cn n e 1 u q 5 e s f 25 year of diagnosis o 7 r e 6 recent infections b m 5 u 4 n 3 c n e u q e s year of infection 2 1

24 Effect of HAART on the epidemic? After the initial decrease following the introduction of HAART, the number of new HIV diagnoses increased again, especially amongst MSM The relative high CD4 cell counts found at diagnosis indicate that these new cases reflect more recent HIV infections The HIV epidemic seems to grow amongst MSM number of diagnoses Number of of incident HIV cases year of diagnosis homosexual men hetero M hetero F IDU %

25 Model Framework Time to diagnosis Reduced risk behaviour Treatment, halts progression and onwards transmission Estimate Data Data Data New Infections New Diagnosed cases New AIDS cases Death Risk-behaviour Magnitude and timing constrained by riskbehaviour and time to diagnosis Simultaneous fitting, can estimate both these parameters

26 HIV concentration over time 7 6 HIV concentration (log) weeks months

27 HIV concentration over time (treated) 7 6 HIV concentration (log) weeks months

28 Predictions past 8 No HAART, R = Cumulative infections 4 2 No earlier diagnosis, R = 1.2 Model fit, R = 1.1 No changes, R =.9 No increase in risk, R= Year Had Increased 3684 Faster HAART there infections diagnosis been risk has prevented has changes caused has prevented ( no infections extra HAART ), 562 infections there would have been 699 fewer infections

29 Predictions future 1 No changes, R = Proportion failing halved, R = 1. Cumulative infections Year Average diagnosis of 1 year, R =.9 Risk as pre-haart, R =.6 All three interventions, R =.5

30 Conclusions Less AIDS Sharp decline of the number of AIDS diagnoses since introduction of HAART AIDS defining illnesses seem to change and are assocated with survival Less death Mortality has decreased since HAART Percentage of HIV related causes of death has declined Mortality amongst HIV positives is still higher as compared tot non HIV infected persons More infections There is an increase in new HIV infections, especially amongst MSM Transmission of resistant HIV is still limited

31 Conclusions HAART only slowed down but not retract the HIV epidemic Reduction of risk behaviour together with HAART have resulted in retraction of the epidemic in the Netherlands Through its effect on behavioural changes, timely diagnosis adds to this retraction Prevention, focussed on reducing transmission risk behaviour was and remains crucial in reducing the HIV epidemic In the Netherlands, testing & counselling should again focus on high risk behaviour with the aim to in time provide effective antiretroviral treatment for those tested positive and to achieve substantial impact on the epidemic

32 Testing & Counselling should be effective Why testing? Timely access to treatment + Opportunity to timely change risk behaviour Impact on the epidemic Next to risk behaviour, transmission depends on the amount of HIV circulating in infected population unaware aware untreated treated

33 Acknowledgements Treating physicians (*Site coordinating physicians) Dr. W. Bronsveld*, Drs. M.E. Hillebrand-Haverkort, Medisch Centrum Alkmaar, Alkmaar; Dr. J.M. Prins*, Dr. J. Branger, Dr. J.K.M. Eeftinck Schattenkerk, Dr. S.E. Geerlings, Drs. J. Gisolf, Dr. M.H. Godfried, Prof.dr. J.M.A. Lange, Dr. K.D. Lettinga, Dr. J.T.M. van der Meer, Drs. F.J.B. Nellen, Dr. T. van der Poll, Prof dr. P. Reiss, Drs. Th.A. Ruys, Drs. R. Steingrover, Drs. G. van Twillert, Drs. J.N. Vermeulen, Drs. S.M.E. Vrouenraets, Dr. M. van Vugt, Dr. F.W.M.N. Wit, Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam; Prof. dr. T.W. Kuijpers, Drs. D. Pajkrt, Dr. H.J. Scherpbier, Emma Kinderziekenhuis, AMC, Amsterdam; Drs. A. van Eeden*, St. Medisch Centrum Jan van Goyen, Amsterdam; Prof. dr. K. Brinkman*, Drs. G.E.L. van den Berk, Dr. W.L. Blok, Dr. P.H.J. Frissen, Dr. J.C. Roos, Drs. W.E.M. Schouten, Dr. H.M. Weigel, Onze Lieve Vrouwe Gasthuis, Amsterdam; Dr. J.W. Mulder*, Dr. E.C.M. van Gorp, Dr. J. Wagenaar, Slotervaart Ziekenhuis, Amsterdam; Dr. J. Veenstra*, St. Lucas Andreas Ziekenhuis, Amsterdam; Prof. dr. S.A. Danner*, Dr. M.A. van Agtmael, Drs. F.A.P. Claessen, Dr. R.M. Perenboom, Drs. A. Rijkeboer, Dr. M.G.A. van Vonderen, VU Medisch Centrum, Amsterdam; Dr. C. Richter*, Drs. J. van der Berg, Ziekenhuis Rijnstate, Arnhem; Dr. R. Vriesendorp*, Dr. F.J.F. Jeurissen, Medisch Centrum Haaglanden, locatie Westeinde, Den Haag; Dr. R.H. Kauffmann*, Drs. K. Pogány, Haga Ziekenhuis, locatie Leyenburg, Den Haag; Dr. B. Bravenboer*, Catharina Ziekenhuis, Eindhoven; Dr. C.H.H. ten Napel*, Dr. G.J. Kootstra, Medisch Spectrum Twente, Enschede; Dr. H.G. Sprenger*, Dr. W.M.A.J. Miesen, Dr. J.T.M. van Leeuwen, Universitair Medisch Centrum, Groningen; Dr. R. Doedens, Dr. E.H. Scholvinck, Universitair Medisch Centrum, Beatrix Kliniek, Groningen; Prof. dr. R.W. ten Kate*, Dr. R. Soetekouw, Kennemer Gasthuis, Haarlem; Dr. D. van Houte*, Dr. M.B. Polée, Medisch Centrum Leeuwarden, Leeuwarden; Dr. F.P. Kroon*, Prof. dr. P.J. van den Broek, Prof. dr. J.T. van Dissel, Dr. E.F. Schippers, Leids Universitair Medisch Centrum, Leiden; Dr. G. Schreij*, Dr. S. van der Geest, Dr. S. Lowe, Dr. A. Verbon, Academisch Ziekenhuis Maastricht; Dr. P.P. Koopmans*, Dr. R. van Crevel, Prof. dr. R. de Groot, Dr. M. Keuter, Dr. F. Post, Dr. A.J.A.M. van der Ven, Dr. A. Warris, Universitair Medisch Centrum St. Radboud, Nijmegen; Dr. M.E. van der Ende*, Dr. I.C. Gyssens, Drs. M. van der Feltz, Dr. J.L Nouwen, Dr. B.J.A. Rijnders, Dr. T.E.M.S. de Vries, Erasmus Medisch Centrum, Rotterdam; Dr. G. Driessen, Dr. M. van der Flier, Dr. N.G. Hartwig, Erasmus Medisch Centrum, Sophia, Rotterdam; Dr. J.R. Juttman*, Dr. C. van de Heul, Dr. M.E.E. van Kasteren, St. Elisabeth Ziekenhuis, Tilburg; Prof. dr. I.M. Hoepelman*, Dr. M.M.E. Schneider, Prof. dr. M.J.M. Bonten, Prof. dr. J.C.C. Borleffs, Dr. P.M. Ellerbroek, Drs. C.A.J.J. Jaspers, Dr. T. Mudrikova, Dr. C.A.M. Schurink, Dr. E.H. Gisolf, Universitair Medisch Centrum Utrecht, Utrecht; Dr. S.P.M. Geelen, Dr. T.F.W. Wolfs, Dr. T. Faber, Wilhelmina Kinderziekenhuis, UMC, Utrecht; Dr. A.A. Tanis*, Ziekenhuis Walcheren, Vlissingen; Dr. P.H.P. Groeneveld*, Isala Klinieken, Zwolle; Dr. J.G. den Hollander*, Medisch Centrum Rijnmond Zuid, locatie Clara, Rotterdam; Dr. A. J. Duits, Dr. K. Winkel, St. Elisabeth Hospitaal/Stichting Rode Kruis Bloedbank, Willemstad, Curaçao; Virologists Dr. N.K.T. Back, M.E.G. Bakker, Prof. dr. B. Berkhout, Dr. S. Jurriaans, Dr. H.L. Zaaijer, Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam; Dr. Th. Cuijpers, CLB Stichting Sanquin Bloedvoorziening, Amsterdam; Dr. P.J.G.M. Rietra, Dr. K.J. Roozendaal, Onze Lieve Vrouwe Gasthuis, Amsterdam; Drs. W. Pauw, Dr. A.P. van Zanten, P.H.M. Smits, Slotervaart Ziekenhuis, Amsterdam; Dr. B.M.E. von Blomberg, Dr. P. Savelkoul, Dr. A. Pettersson, VU Medisch Centrum, Amsterdam; Dr. C.M.A. Swanink, Ziekenhuis Rijnstate, Arnhem; Dr. P.F.H. Franck, Dr. A.S. Lampe, HAGA ziekenhuis, locatie Leyenburg, Den Haag; C.L. Jansen, Medisch Centrum Haaglanden, locatie Westeinde, Den Haag; Dr. R. Hendriks, Streeklaboratorium Twente, Enschede; C.A. Benne, Streeklaboratorium Groningen, Groningen; Dr. D. Veenendaal, Dr. J. Schirm, Streeklaboratorium Volksgezondheid Kennemerland, Haarlem; Dr. H. Storm, Drs. J. Weel, Drs. J.H. van Zeijl, Laboratorium voor de Volksgezondheid in Friesland, Leeuwarden; Prof. dr. A.C.M. Kroes, Dr. H.C.J. Claas, Leids Universitair Medisch Centrum, Leiden; Prof. dr. C.A.M.V.A. Bruggeman, Drs. V.J. Goossens, Academisch Ziekenhuis Maastricht, Maastricht; Prof. dr. J.M.D. Galama, Dr. W.J.G. Melchers, Y.A.G. Poort, Universitair Medisch Centrum St. Radboud, Nijmegen; Dr. G.J.J. Doornum, Dr. H.G.M. Niesters, Prof. dr. A.D.M.E. Osterhaus, Dr. M. Schutten, Erasmus Medisch Centrum, Rotterdam; Dr. A.G.M. Buiting, C.A.M. Swaans, St. Elisabeth Ziekenhuis, Tilburg; Dr. C.A.B. Boucher, Dr. R. Schuurman, Universitair Medisch Centrum Utrecht, Utrecht; Dr. E. Boel, Dr. A.F. Jansz, Catharina Ziekenhuis, Eindhoven; Pharmacologists Dr. A. Veldkamp, Medisch Centrum Alkmaar, Alkmaar; Prof. dr. J.H. Beijnen, Dr. A.D.R. Huitema, Slotervaart Ziekenhuis, Amsterdam; Dr. D.M. Burger, Dr. P.W.H. Hugen, Universitair Medisch Centrum St. Radboud, Nijmegen; Drs. H.J.M. van Kan, Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam; HIV Monitoring Foundation Governing Board 26 Drs. M.A.J.M. Bos, treasurer (from July 26), ZN; Prof. dr. R.A. Coutinho, observer, RIVM; Prof. dr. S.A. Danner, chairman, NVAB; Prof. dr. J. Goudsmit, member, AMC-UvA; Prof. dr. L.J. Gunning-Schepers, member, NFU; Dr. D.J. Hemrika, secretary, NVZ; Drs. J.G.M. Hendriks, treasurer (until July 26), ZN; Drs. H. Polee, member, Dutch HIV Association; Drs. M.I. Verstappen, member, GGD; Dr. F. de Wolf, director, HMF; Advisory Board Prof. dr. R.M. Anderson, Imperial College, Faculty of Medicine, Dept. Infectious Diseases Epidemiology, London, United Kingdom; Prof. dr. J.H. Beijnen, Slotervaart Hospital, Dept. of Pharmacology, Amsterdam; Dr. M.E. van der Ende, Erasmus Medical Centre, Rotterdam; Dr. P.H.J. Frissen (until February 26), Onze Lieve Vrouwe Gasthuis, Dept. of Internal Medicine, Amsterdam;

34 Acknowledgements Prof. dr. R. de Groot, Sophia Children s Hospital, Rotterdam; Prof. dr. I.M. Hoepelman, UMC Utrecht, Utrecht; Dr. R.H. Kauffmann, Leyenburg Hospital, Dept. of Internal Medicine, Den Haag; Prof. dr. A.C.M. Kroes, LUMC, Clinical Virological Laboratory, Leiden; Dr. F.P. Kroon (vice chairman), LUMC, Dept. of Internal Medicine, Leiden; Dr. M.J.W. van de Laar, RIVM, Centre for Infectious Diseases Epidemiology, Bilthoven; Prof. dr. J.M.A. Lange (chairman), AMC, Dept. of Internal Medicine, Amsterdam; Prof. dr. A.D.M.E. Osterhaus (until February 26), Erasmus Medical Centre, Dept. of Virology, Rotterdam; Prof. dr. G. Pantaleo, Hôpital de Beaumont, Dept. of Virology, Lausanne, Switzerland; Dhr. C. Rümke, Dutch HIV Association, Amsterdam; Prof. dr. P. Speelman, AMC, Dept of Internal Medicine, Amsterdam; Working group Clinical Aspects Dr. K. Boer, AMC, Dept. of Obstetrics/Gynaecology, Amsterdam; Prof. dr. K. Brinkman (vice chairman), OLVG, Dept of Internal Medicine, Amsterdam; Dr. D.M. Burger (subgr. Pharmacology), UMCN St. Radboud, Dept. of Clinical Pharmacy, Nijmegen; Dr. M.E. van der Ende (chairman), Erasmus Medical Centre, Dept. of Internal Medicine, Rotterdam; Dr. S.P.M. Geelen, UMCU- WKZ, Dept of Paediatrics, Utrecht; Dr. J.R. Juttmann, St. Elisabeth Hospital, Dept. of Internal Medicine, Tilburg; Dr. R.P. Koopmans, UMCN-St. Radboud, Dept. of Internal Medicine, Nijmegen; Prof. dr. T.W. Kuijpers, AMC, Dept. of Paediatrics, Amsterdam; Dr. W.M.C. Mulder, Dutch HIV Association, Amsterdam; Dr. C.H.H. ten Napel, Medisch Spectrum Twente, Dept. of Internal Medicine, Enschede; Dr. J.M. Prins, AMC, Dept. of Internal Medicine, Amsterdam; Prof. dr. P. Reiss (subgroup Toxicity), AMC, Dept. of Internal Medicine, Amsterdam; Dr. G. Schreij, Academic Hospital, Dept. of Internal Medicine, Maastricht; Drs. H.G. Sprenger, Academic Hospital, Dept. of Internal Medicine, Groningen; Dr. J.H. ten Veen, OLVG, Dept. of Internal Medicine, Amsterdam; Working group Virology Dr. N.K.T. Back, AMC, Dept. of Human Retrovirology, Amsterdam; Dr. C.A.B. Boucher, UMCU, Eykman-Winkler Institute, Utrecht; Dr. H.C.J. Claas, LUMC, Clinical Virological Laboratory, Leiden; Dr. G.J.J. Doornum, Erasmus Medical Centre, Dept. of Virology, Rotterdam; Prof. dr. J.M.D. Galama, UMCN- St. Radboud, Dept. of Medical Microbiology, Nijmegen; Dr. S. Jurriaans, AMC, Dept. of Human Retrovirology, Amsterdam; Prof. dr. A.C.M. Kroes (chairman), LUMC, Clinical Virological Laboratory, Leiden; Dr. W.J.G. Melchers, UMCN St. Radboud, Dept. of Medical Microbiology, Nijmegen; Prof. dr. A.D.M.E. Osterhaus, Erasmus Medical Centre, Dept. of Virology, Rotterdam; Dr. P. Savelkoul, VU Medical Centre, Dept. of Medical Microbiology, Amsterdam; Dr. R. Schuurman, UMCU, Dept. of Virology, Utrecht; Dr. A.I. van Sighem, HIV Monitoring Foundation, Amsterdam; Data collectors Y.M. Bakker, C.R.E. Lodewijk, Y.M.C. Ruijs-Tiggelman, D.P. Veenenberg-Benschop, I. Farida, Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam; C. Leenders, R. Vergoossens, Academisch Ziekenhuis Maastricht, Maastricht; B. Korsten, S. de Munnik, Catharina Ziekenhuis, Eindhoven; M. Bendik, C. Kam-van de Berg, A. de Oude, T. Royaards, Erasmus Medisch Centrum, Rotterdam; G. van der Hut, Haga Ziekenhuis, locatie Leyenburg, Den Haag; A. van den Berg, A.G.W. Hulzen, Isala Klinieken, Zwolle; P. Zonneveld, Kennemer Gasthuis, Haarlem; M.J. van Broekhoven-Kruijne, W. Dorama, Leids Universitair Medisch Centrum, Leiden; D. Pronk, F.A. van Truijen-Oud, Medisch Centrum Alkmaar, Alkmaar; S. Bilderbeek, Medisch Centrum Haaglanden, locatie Westeinde, Den Haag; A. Ballemans, S. Rotteveel, Medisch Centrum Leeuwarden, Leeuwarden; J. Smit, J. den Hollander, Medisch Centrum Rijnmond Zuid, locatie Clara, Rotterdam; H. Heins, H. Wiggers, Medisch Spectrum Twente, Enschede; B.M. Peeck, E.M. Tuyn-de Bruin, Onze Lieve Vrouwe Gasthuis, Amsterdam; C.H.F. Kuiper, Stichting Medisch Centrum Jan van Goyen, Amsterdam; E. Oudmaijer-Sanders, Slotervaart Ziekenhuis, Amsterdam; R. Santegoeds, B. van der Ven, St. Elisabeth Ziekenhuis, Tilburg; M. Spelbrink, St. Lucas Andreas Ziekenhuis, Amsterdam; M. Meeuwissen, Universitair Medisch Centrum St. Radboud, Nijmegen; J. Huizinga, C.I. Nieuwenhout, Universitair Medisch Centrum Groningen, Groningen; M. Peters, C.S.A.M. van Rooijen, A.J. Spierenburg, Universitair Medisch Centrum Utrecht, Utrecht; C.J.H. Veldhuyzen, VU Medisch Centrum, Amsterdam; C.W.A.J. Deurloo-van Wanrooy, M. Gerritsen, Ziekenhuis Rijnstate, Arnhem; Y.M. Bakker, Ziekenhuis Walcheren, Vlissingen; S. Meyer, B. de Medeiros, S. Simon, S. Dekker, Y.M.C. Ruijs-Tiggelman, St. Elisabeth Hospitaal/Stichting Rode Kruis Bloedbank, Willemstad, Curaçao; Personnel HIV Monitoring Foundation Amsterdam E.T.M. Bakker, assistant personnel (until September 26); Y.M. Bakker, data collection AMC; R.F. Beard, registration & patient administration; Drs. D.O. Bezemer, data analysis; D. de Boer, financial controlling; I. de Boer, assistant personnel (from November 26); M.J. van Broekhoven-Kruijne, data collection LUMC; S.H. Dijkink, assistant data monitor (from March 26); I. Farida, data collection AMC; D.N. de Gouw, communication manager; Drs. L.A.J. Gras, data analysis; Drs. S. Grivell, data monitor ; Drs. M.M. Hillebregt, data monitor; Drs. A.M. Kesselring, data analysis (from January 26); Drs. B. Slieker, data monitoring; C.H.F. Kuiper, data collection St. Medisch Centrum Jan van Goyen; C.R.E. Lodewijk, data collection AMC; Drs. H.J.M. van Noort, assistant financial controlling; B.M. Peeck, data collection OLVG; Oosterpark; Dr. T. Rispens, data monitor (until April 26); Y.M.C. Ruijs-Tiggelman, data collection AMC; Drs. G.E. Scholte, executive secretary; Dr. A.I. van Sighem, data analysis; Ir. C. Smit, data analysis; E.M. Tuyn-de Bruin, data collection OLVG Oosterpark; Drs. E.C.M. Verkerk, data monitoring (from June 26); D.P. Veenenberg-Benschop, data collection AMC; Y.T.L. Vijn, data collection OLVG Prinsengracht (until May 26); C.W.A.J. Deurloo-van Wanrooy, data collection Rijnstate; Dr. F. de Wolf, director; Drs. S. Zaheri, data quality control; Drs. J.A Zeijlemaker, editor (until April 26); Drs. S. Zhang, data analysis (from February 26)

35 Time to death within 3 years of starting HAART according to CDC-C classification in 3198 therapy naïve patients starting with <2 CD4 cells/mm 3 1 HR (95% CI) PML NHL DEM MAC HSV PNR KSA ISO TOX WAS ECA CMV TBC MYC CRS PCP CRC Model adjusted for calendar year of starting HAART, CD4 cell count and HIV RNA at starting HAART, age, gender and transmission risk group. Hazard ratio s of the specific CDC-C diseases are relative to no CDC-event. PML progressive multifocal leucoencephalopathy, NHL non-hodgkins lymphoma (including primary brain lymphoma), DEM AIDS dementia complex, MAC mycobacterium avium/kansasii, HSV herpes simplex virus, PNR pneumonia recurrent, KSA Kaposi s sarcoma, ISO Isosporiasis, TOX Toxoplasmosis of the brain, WAS Wasting syndrome, ECA esophageal candidiasis, CMV cytomegalovirus disease, TBC tuberculosis, MYC mycobacterium atypical, CRS cryptosporidiosis, PCP Pneumocystis carinii pneumonia, CRC Cryptococcosis extrapulmonar

36 Cumulative number of HIV infections Predictions future Assuming a constant rate of imported cases Year All as in 24 R(t) = 1.1 Average diagnosis 3 1 year R(t) =.9 Risk-behavior 66% lower R(t)=.6 (as pre-haart)

37 Simulations past N cumulative of HIV infections Year No HAART R(t) = 1.5 No earlier diagnosis R(t) = 1.2 Modelfit R(t)=1.1 As in 1994 R(t)=.9 No increase in risk R(t) =.6

38 HIV Monitoring Foundation