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
Data
New AIDS cases
Death
Data
New Infections New Diagnosed cases
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
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
1992
1991
1990
1989
1988
1987
1986
1985
1984
0
1983
• 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
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 (10.000-28.000)
Op de Coul & Van Sighem, 2006
As per mid 2006:
Gras et al, 2006
12.059
12059 patients are registered
1200
1000
N
800
600
400
200
06
04
20
02
20
00
20
98
20
96
19
94
19
92
19
90
19
88
19
86
19
84
19
82
19
19
19
80
0
year of HIV diagnosis
100
80
60
%
40
20
% male
% female
year of diagnosis
05
03
20
01
20
20
99
19
97
19
95
19
93
19
91
89
19
87
19
19
85
19
83
0
19
• 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 (10.000-28.000)
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
AIDS incidence per 100 person-years
• 2048 new AIDS diagnoses
from 6 weeks after HIV
diagnosis
• 1598 after 1996
• Average AIDS incidence:
2.9/100 person-years
• In 1996: 9.6 and in 2005: 2
• Since 2003 no major changes
• 1066 AIDS diagnoses after
start HAART
• 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
AIDS incidence per 100 person-years
3468 AIDS diagnoses
20
After HIV diagnosis
15
10
5
0
1996
1998
2000 2002
calendar year
2004
2006
After start of HAART
15
10
5
0
1996
1998
2000 2002
calendar year
2004
2006
Time to death within 3 years of
starting HAART according to CDC-C
classification
HR (95% CI)
100
10
CRC
PCP
CRS
MYC
TBC
CMV
ECA
WAS
TOX
ISO
KSA
HSV
MAC
DEM
NHL
PML
0.1
PNR
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-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
How many died?
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
Since 1996:
Gras et al, 2006
985
985 deaths
Mortality after HIV diagnosis
6
5
4
3
2
1
0
1996
7
mortality per 100 person-years
• Av mortality ratio: 1.48 per 100
person-years
• Mortality in the total group does
not change: 1.16 in 1996 and
0.84 in 2006
• Mortality is still higher as
compared to the non-infected
population, but comparable 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.
mortality per 100 person-years
7
1998
2000 2002
calendar year
2004
2006
Mortality after start of HAART
6
5
4
3
2
1
0
1996
1998
2000 2002
calendar year
2004
2006
Causes of death
100%
non-HIV-related
80%
pro po rtio n
• In 1996:
• 76% HIV related
• 10% non HIV related
• 14% unknown
• In 2005:
• 39% HIV related
• 50% non HIV related
• 11% unknown
60%
40%
HIV-related
20%
unknown
0%
1996
1998
2000
2002
calendar year
2004
2006
Standardised Mortality Ratio
• SMR r : patient has r times higher probability of death than a
non-infected individual
25
women
25
CD4=350
20
men
CD4=200
CD4=350
20
CD4=600
15
SMR
SMR=1
CD4=600
SMR=1
15
NL diabetes
10
UK diabetes
NL diabetes
10
5
5
0
0
20
30
40
50
age [years]
60
Source diabetes data: Baan et al., Epidemiology 2004;
Laing et al., Diabet Med. 1999
CD4=200
70
UK diabetes
20
30
40
50
age [years]
60
70
Predicted survival probability
• 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
• Predicted probability to reach
a specific age for an
asymptomatic male patient
diagnosed at the age of 34.
0.8
0.6
uninfected
0.4
HIV CD4 600
HIV CD4 350
0.2
HIV CD4 200
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
8292 HAART treated: Virological effect
6
log HIV-RN A copies/m l plasm a
• 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
5
4
3
2
all
1
0
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
• In older patients and patients with viral rebounds after start of
HAART the increase in CD4 cells is less.
>500
HIV resistance in treated patients
0.6
fraction patients failing on therapy
• HAART failure decreased in
ART experienced patients
• Amongst naive patients the
percentage of HAART
failures increased slowly
• In 80% of the patients
experiencing virological
failure during treatment
resistance is found
pre-treated
naïve
0.5
0.4
0.3
0.2
0.1
0.0
1996
1998
2000 2002
kalenderjaar
2004
2006
• However: Resistance is measured in only 17% of the patients with
virological failure during HAART
Transmission of resistant HIV
B
100
250
percentage resistant
• Since 2001 resistance is
found in 7.7% of the new HIV
diagnoses
• In 14 patients high-level
resistance
80
200
newly diagnosed
70
60
150
50
40
100
30
20
50
10
0
0
1995
2000
year of diagnosis
2005
100
70
90
60
80
recent infections
70
50
60
40
50
40
30
30
20
20
10
10
0
0
1995
2000
year of infection
2005
number of sequences
A
percentage resistant
• 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
number of sequences
90
Effect of HAART on the epidemic?
number of diagnoses
500
400
hom osex ual m en
hetero M
hetero F
IDU
37%
300
200
100
0
Nu m ber of of i n c i den t H IV c as es
• 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
1995
600
2000
year of diagnosis
2005
500
400
300
200
100
0
1980 1985 1990 1995 2000 2005
Model Framework
Time to diagnosis
Estimate
Reduced Treatment, halts
risk
progression and onwards
behaviour transmission
Data
New Infections New Diagnosed cases
Risk-behaviour
Data
Data
New AIDS cases
Death
Magnitude and timing constrained by risk-behaviour
and time to diagnosis
Simultaneous fitting, can estimate both these
parameters
HIV concentration over time
weeks
months
HIV concentration over time (treated)
weeks
months
Predictions past
8000
No HAART, R = 1.5
Cumulative
Cumulative infections
infections
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
2000
2002
2004
Had
there
been
no changes
(“noinfections
HAART”),
there
3684
infections
HAART
has
4165
Increased
riskprevented
has
caused
2099
extra
Faster
diagnosis
has prevented
562 infections
would have been 699 fewer infections
Predictions future
10000
No changes, R = 1.1
Proportion failing halved, R = 1.0
Cumulative infections
8000
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
2010
2008
Year
2012
2014
Conclusions
● Less AIDS
● Less death ● More infections
•
• Sharp decline of • Mortality has
decreased since
the number of
HAART
AIDS diagnoses
since introduction
• Percentage of HIV
of HAART
related causes of •
death has declined
• AIDS defining
• Mortality amongst
illnesses seem
HIV positives is still
to change and
higher as compared
are assocated
tot non HIV infected
with survival
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. VeenenbergBenschop, 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)