Scaling up testing and counselling as it looks from treatment data monitoring perspectives: The applied research outcomes and the policy implications it.

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 WolfHIV Monitoring FoundationAmsterdam, The Netherlandswww.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

Death

Data

Data

New Diagnosed cases New AIDS casesNew Infections

Data

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

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

• 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.

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Deaths

AIDS cases

De Boer et al., RIVM 2006Sources AIDS: AIDS registration Health Inspectorate <2000, HMF ≥2000.Sources deaths: CBS <2002, HMF ≥2002.

• After introduction of HAART, the number of AIDS diagnoses and HIV death declined

Ten years HAART in the Netherlands1. 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?

How many are infected?

18.500 (10.000-28.000)2005 estimate:Op de Coul & Van Sighem, 2006

18.500 HIV infected persons

0.00%

0.05%

0.10%

0.15%

0.20%

0.25%

1980 1985 1990 1995 2000 2005 2010

Pre

vale

nce

(%)

adul

ts

Op de Coul & Van Sighem

• 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?

18.500 (10.000-28.000)Number HIV+:Op de Coul & Van Sighem, 2006

12.059As per mid 2006:Gras et al, 2006

12059 patients are registered

• 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

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How many got AIDS?

18.500 (10.000-28.000)Number HIV+:Op de Coul & Van Sighem, 2006

12.059N registered:Gras et al, 2006

3.468At or after HIV diagnose:Gras et al, 2006

3468 AIDS diagnoses• 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

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calendar year1996 1998 2000 2002 2004 2006

After HIV diagnosis

After start of HAART

Time to death within 3 years of starting HAART according to CDC-C classification

0.1

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10

100P

ML

NH

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DE

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CR

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CR

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HR

(95

% C

I)

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 sarcomaISO: IsosporidiasisTOX: Toxoplasmosis

of the brainWAS: Wasting

syndromeECA: Oesophageal

candidiasisCMV:

Cytomegalovirus diseaseTBC: TuberculosisMYC: Atypical

Mycobacterium infectionCRS:

CryptosporidiosisPCP:Pneumocystis carinii

pneumoniaCRC: Extrapulmonar

Cryptococcosis

How many died?

18.500 (10.000-28.000)Number HIV+:Op de Coul & Van Sighem, 2006

12.059N registered:Gras et al, 2006

3.468AIDS:Gras et al, 2006

985Since 1996:Gras et al, 2006

985 deaths• 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.

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Mortality after HIV diagnosis

Mortality after start of HAART

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

non-HIV-related

HIV-related

unknown

Standardised Mortality Ratio

• SMR r : patient has r times higher probability of death than a non-infected individual

women

men

Source diabetes data: Baan et al., Epidemiology 2004; Laing et al., Diabet Med. 1999

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

How many patients are (not) on HAART?

18.500 (10.000-28.000)Number HIV+:Op de Coul & Van Sighem, 2006

12.059N registered:Gras et al, 2006

3.468

985Deaths:Gras et al, 2006

8292In 1996:Gras et al, 2006 Untreated: 2136

AIDS:Gras et al, 2006

8292 HAART treated: Virological effect• 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

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diagnosis startHAART

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Immunological effect of HAART

• 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

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Weeks from starting HAART

Dif

fere

nc

e f

rom

ba

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line

(c

ells

/mm

3)

<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.

HIV resistance in treated patients• 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-treatednaïve

fract

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patie

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kalenderjaar1996 1998 2000 2002 2004 2006

• However: Resistance is measured in only 17% of the patients with virological failure during HAART

Transmission of resistant HIV

newly diagnosed

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70• 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

• Since 2001 resistance is found in 7.7% of the new HIV diagnoses

• In 14 patients high-level resistance

Effect of HAART on the epidemic?

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homosexual menhetero Mhetero FIDU

• 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

37%

Model Framework

Death

Data

Data

New Diagnosed cases New AIDS cases

Estimate

New Infections

Data

Time to diagnosis

Reduced risk behaviour

Treatment, halts progression and onwards transmission

Magnitude and timing constrained by risk-behaviour and time to diagnosis

Simultaneous fitting, can estimate both these parameters

Risk-behaviour

HIV concentration over time

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conce

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log)

weeks months

HIV concentration over time (treated)

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HIV

conce

ntr

ati

on (

log)

weeks months

Predictions pastNo HAART, R = 1.5

No earlier diagnosis, R = 1.2

No increase in risk, R= 0.6

No changes, R = 0.9

Model fit, R = 1.1

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3684 infectionsHAART has prevented 4165 infections

Increased risk has caused 2099 extra infections

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infe

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Faster diagnosis has prevented 562 infections

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Had there been no changes (“no HAART”), there would have been 699 fewer infections

Predictions future

No changes, R = 1.1

Proportion failing halved, R = 1.0

Risk as pre-HAART, R = 0.6

Average diagnosis of 1 year, R = 0.9

All three interventions, R = 0.5

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Conclusions

• Sharp decline of the number of AIDS diagnoses since introduction of HAART

• Mortality has decreased since HAART

• There is an increase in new HIV infections, especially amongst MSM

● Less AIDS

• AIDS defining illnesses seem to change and are assocated with survival

• Percentage of HIV related causes of death has declined

• Mortality amongst HIV positives is still higher as compared tot non HIV infected persons

• Transmission of resistant HIV is still limited

● Less death● More infections

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

+

AcknowledgementsTreating 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;

AcknowledgementsProf. 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, 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 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)