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 www.hiv-monitoring.nl
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
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 New Infections New Diagnosed cases
Data New AIDS cases
Data 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)
HIV and AIDS current situation in the Netherlands ● Less AIDS ● Less Death ● More Infections
Less AIDS and death
•
600
500
Deaths AIDS cases
400
300
200
100
2005
2004
2003
2001
2002
1999
2000
1998
1997
1996
1995
1993
1994
1991
1992
1989
1990
1988
1987
1986
1985
0 1984
•
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
1983
•
De Boer et al., RIVM 2006 Sources AIDS: AIDS registration Health Inspectorate <2000, HMF ≥2000. Sources deaths: CBS <2002, HMF ≥2002.
Ten years HAART in the Netherlands 1. 2. 3. 4. 5. 6. 7.
How many are infected? How many infected are registered? How many got AIDS? How many died? How many are treated? And not treated? What’s the effect of HAART on the epidemic?
How many are infected? 2005 estimate: Op de Coul & Van Sighem, 2006
18.500
(10.000-28.000)
18.500 HIV infected persons Prevalence (%) adults
0.25%
• • • •
0.20% 0.15% 0.10% 0.05% Op de Coul & Van Sighem
0.00% 1980 1985 1990 1995 2000 2005 2010
HIV prevalence amongst adults (age 15-49): 0.23% Amongst MSM: 5.3% Amongst iv drug users: 5.3% Amongst CSW: 2.7%
How many HIV positives are registered? Number HIV+:
18.500
Op de Coul & Van Sighem, 2006
As per mid 2006: Gras et al, 2006
12.059
(10.000-28.000)
12059 patients are registered 1200
N
400 200
6 0
0
0
2
2
2
0
0
4
2
0
0
0 0
2
1
9
9
9 9
1
1
8
6
4
2
9 9
9 9
1
1
1
9
9
0
8
6
9
9 1
8
8
4
2
8 9
1
1
1
9
9
8
8
0
0
year of HIV diagnosis
100 80 60 40 20
% male % female
0
5
3
0 2
0
0
1
year of diagnosis
2
2
0
0
9 9
9 1
9
9
7
5 9
1
1
9
9
3
1
9 1
1
9
9
9
7
8
1
9
8 9
1
9
8
5
3
0 8
•
600
9
•
800
1
•
1000
1
•
In 2005 964 new HIV diagnoses In total 9254 men and 2699 women >13 years of age In addition: 106 boys and girls ≤13 years Percentage of men is increasing since 2003 Main risk group: MSM
%
•
How many got AIDS? Number HIV+:
18.500
Op de Coul & Van Sighem, 2006
N registered:
12.059
Gras et al, 2006
At or after HIV diagnose: Gras et al, 2006
3.468
(10.000-28.000)
n e o c s n re e d p i c 0 n 0 i 1 S rD e I p A
3468 AIDS diagnoses • • • • • • •
•
2048 new AIDS diagnoses from 6 weeks after HIV diagnosis e 1598 after 1996 c n Average AIDS incidence: 2.9/100 e person-years d i In 1996: 9.6 and in 2005: 2c n i Since 2003 no major changes 1066 AIDS diagnoses afterSD start I HAART A AIDS incidence after start HAART decreases sharply from 14.8 in 1996 to 2.06 in 2005. Number of AIDS diagnoses in 2005: 276
20
After HIV diagnosis
15 10 5 0 1996
1998
20
2000 2002 2004 calendar year
2006
After start of HAART
15 10 5 0 1996
1998
2000 2002 2004 calendar year
2006
Time to death within 3 years of starting HAART according to CDC-C classification 100
Progressive multifocal leucoencephalopathy NHL:Non-Hodgkin lymphoma DEM: AIDS dementia complex MAC: Mycobacterium avium/kansasii 10 HSV: Herpes simplex virus PNR: Recurrent pneumonia KSA:Kaposi’s sarcoma ISO: Isosporidiasis TOX: Toxoplasmosis of the 1 brain WAS: Wasting syndrome ECA: Oesophageal candidiasis CMV: Cytomegalovirus disease TBC:Tuberculosis MYC: Atypical Mycobacterium 0.1 infection CRS: Cryptosporidiosis Pneumocystis carinii Model adjusted for calendar year of starting HAART, CD4 cell count and HIV RNA PCP: pneumonia at starting HAART, age, gender and transmission risk group. Hazard ratio’s of the CRC: Extrapulmonar specific CDC-C diseases are relative to no CDC-event. Cryptococcosis
CRC
PCP
CRS
MYC
TBC
CMV
ECA
WAS
TOX
ISO
KSA
PNR
HSV
MAC
DEM
NHL
PML
HR (95% CI)
PML:
How many died? Number HIV+:
18.500
Op de Coul & Van Sighem, 2006
N registered:
12.059
Gras et al, 2006
AIDS:
3.468
Gras et al, 2006
Since 1996: Gras et al, 2006
985
(10.000-28.000)
985 deaths • •
•
• •
e e yp y n t o si rl a e t p r o 0 m 0
Av mortality ratio: 1.48 per1100 person-years r e Mortality in the total groupp does not change: 1.16 in 1996 y t and 0.84 in 2006 i l Mortality is still higher as a t compared to the non-infected r population, but comparableom 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 2005.
7 6
Mortality after HIV diagnosis
5 4 3 2 1 0 1996 1998 2000 2002 2004 2006 calendar year 7 6
Mortality after start of HAART
5 4 3 2 1 0 1996 1998 2000 2002 2004 2006 calendar year
Causes of death
•
In 1996: • 76% HIV related • 10% non HIV related • 14% unknown In 2005: • 39% HIV related • 50% non HIV related • 11% unknown
100%
non-HIV-related
80% proportion
•
60% 40%
HIV-related
20%
unknown
0% 1996
1998
2000
2002
calendar
2004
year
2006
Standardised Mortality Ratio •
SMR r : patient has r times higher probability of death than a non-infected individual 25
women
20
CD4=200 CD4=350
25
men
20
SMR
CD4=600 SMR=1
15
UK diabetes
SMR=1
15
NL diabetes
5
0
0 30
40 50 age [years]
60
Source diabetes data: Baan et al., Epidemiology 2004; Laing et al., Diabet Med. 1999
UK diabetes
10
5
20
CD4=350 CD4=600
NL diabetes 10
CD4=200
70
20
30
40 50 age [years]
60
70
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 70 • 72% non-infected • 68% CD4 600 cells/mm3 • 67% CD4 350 cells/mm3 • 65% CD4 200 cells/mm3 • 58% CD4 50 cells/mm3
1
surival probability
•
0.8 0.6 uninfected HIV CD4 600
0.4
HIV CD4 350 HIV CD4 200
0.2
HIV CD4 50
0 30
40
50
60
70
age [years]
80
90
100
How many patients are (not) on HAART? Number HIV+:
18.500
(10.000-28.000)
Op de Coul & Van Sighem, 2006
N registered:
12.059
Gras et al, 2006
AIDS:
3.468
Gras et al, 2006
Deaths:
985
Gras et al, 2006
In 1996: Gras et al, 2006
8292
Untreated: 2136
•
• •
•
After the first 24 weeks of HAART, the amount of HIV in blood has declined 3 logs 80% are below the detection threshold 388/5304 naïve patients show viral rebounds after initial success Incidence of viral rebound is 3.2 per 100 person-years of follow-up
log HIV-RNA copies/ml plasma
8292 HAART treated: Virological effect 6 5 4 3 2 1 0
all IQR IQR diagnosis
start HAART
24 wks
48 wks
•
• •
•
Patients continuously on HAART do show an increase of CD4 cells from median 221/mm3 at start to 607/mm3 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)
Immunological effect of HAART 500 450 400 350 300 250 200 150 100 50 0 0
48
96 144 192 240 288 336
Weeks from starting HAART <50
50-200
200-350
350-500
>500
In older patients and patients with viral rebounds after start of HAART the increase in CD4 cells is less.
f s t n e i t a p
HIV resistance in treated patients • •
•
•
n in HAART failure decreased o ART experienced patients i t Amongst naive patients cthe percentage of HAART ar failures increased slowlyf In 80% of the patients experiencing virological failure during treatment resistance is found
0.6 0.5
pre-treated naïve
0.4 0.3 0.2 0.1 0.0 1996
1998 2000 2002 2004 kalenderjaar
2006
However: Resistance is measured in only 17% of the patients with virological failure during HAART
t s i s e r
Transmission of resistant HIV •
•
•
•
e g a t n e tc n r a e tp s i s e r
Since 2001 resistance is found in 7.7% of the new HIV diagnoses In 14 patients high-level resistance e g a t n e c r e p
In 6.0% of the recent infections one or more mutations associated with resistance are found 3 patients with high-level resistance; 1 to all drug classes
B 100 90 80 70 60 50 40 30 20 10 0
A
100 90 80 70 60 50 40 30 20 10 0
newly diagnosed
1995
2000 year of diagnosis
recent infections
c n e u q e s f o r e b sm eu cn n e u q e s
250 200 150 100 50
0 2005 f o 70 r 60 e b 50 m u 40 n 30 20 10
1995
2000 year of infection
2005
0
•
•
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 of incident HIV cases
•
number of diagnoses
Effect of HAART on the epidemic? 500 400
homosexual hetero M hetero F IDU
men
37%
300 200 100 0 1995 600
2000 2005 year of diagnosis
500 400 300 200 100 0 1980 1985 1990 1995 2000 2005
Model Framework Time to diagnosis Estimate
Reduced Treatment, halts risk progression and behaviour onwards transmission
Data
New Infections New Diagnosed cases
Risk-behaviour
Data New AIDS cases
Magnitude and timing constrained by riskbehaviour and time to diagnosis Simultaneous fitting, can estimate both these parameters
Data Death
HIV concentration over time 7
HIV concentration (log)
6
5
4
3
2
weeks 1
months
HIV concentration over time (treated) 7
HIV concentration (log)
6
5
4
3
2
weeks 1
months
Predictions past 8000 8000
No HAART, R = 1.5
Cumulative Cumulative infections infections
6000 6000
No earlier diagnosis, R = 1.2
4000
Model fit, R = 1.1 No changes, R = 0.9
2000
No increase in risk, R= 0.6
0 1994
1996
1998
Year Year
2000
2002
2004
Had there been no changes (“noinfections HAART”), there 3684 HAART infections has prevented 4165 Increased Faster diagnosis risk has caused has prevented 2099 extra 562infections infections would have been 699 fewer infections
Predictions future 10000 No changes, R = 1.1
Cumulative infections
8000
Proportion failing halved, R = 1.0
6000 Average diagnosis of 1 year, R = 0.9
4000
2000
Risk as pre-HAART, R = 0.6 All three interventions, R = 0.5
0 2004
2006
2008
2010 Year
2012
2014
Conclusions ● Less AIDS •
•
● Less death
Sharp decline of • the number of AIDS diagnoses since introduction • of HAART AIDS defining illnesses seem to change and are assocated with survival
•
Mortality has decreased since HAART
● More infections •
Percentage of HIV related causes of • death has declined Mortality amongst HIV positives is still higher as compared tot non HIV infected persons
There is an increase in new HIV infections, especially amongst MSM Transmission of resistant HIV is still limited
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
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
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 2006 Drs. M.A.J.M. Bos, treasurer (from July 2006), 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 2006), 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 2006), Onze Lieve Vrouwe Gasthuis, Dept. of Internal Medicine, Amsterdam;
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 2006), 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, UMCUWKZ, 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 2006); 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 2006); M.J. van Broekhoven-Kruijne, data collection LUMC; S.H. Dijkink, assistant data monitor (from March 2006); 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 2006); 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 2006); 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 2006); D.P. Veenenberg-Benschop, data collection AMC; Y.T.L. Vijn, data collection OLVG Prinsengracht (until May 2006); 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 2006); Drs. S. Zhang, data analysis (from February 2006)
Time to death within 3 years of starting HAART according to CDC-C classification in 3198 therapy naïve patients starting with <200 CD4 cells/mm3
HR (95% CI)
100
10
1
CRC
PCP
CRS
MYC
TBC
CMV
ECA
WAS
TOX
ISO
KSA
PNR
HSV
MAC
DEM
NHL
PML
0.1
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
Cumulative number of HIV infections
Predictions future Assuming a constant rate of imported cases
10000
All as in 2004 R(t) = 1.1
8000 6000
Average diagnosis 3 1 year R(t) = 0.9
4000 2000 0 2005
Risk-behavior 66% lower R(t)=0.6 (as pre-HAART)
2007
2009 2011 Year
2013
Ncumulative of HIV infections
Simulations past 8000 No HAART R(t) = 1.5
6000 No earlier diagnosis R(t) = 1.2
4000
Modelfit R(t)=1.1 As in 1994 R(t)=0.9
2000 No increase in risk R(t) = 0.6
0 1995
1997
1999 Year
2001
2003
HIV Monitoring Foundation
