Frank de Wolf

Academic Medical Center (AMC), Amsterdamo, North Holland, Netherlands

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Publications (238)1451.29 Total impact

  • S Zhang, A van Sighem, A Kesselring, L Gras, Jm Prins, E Hassink, R Kauffmann, C Richter, F de Wolf, P Reiss
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    ABSTRACT: Certain non-AIDS-related diseases have been associated with immunodeficiency and HIV RNA levels in HIV-infected patients on combination antiretroviral therapy (cART). We aimed to investigate these associations in patients not yet on cART, when potential antiretroviral-drug-related effects are absent and variation in RNA levels is greater. Associations between, on the one hand, time-updated CD4 counts and plasma HIV RNA and, on the other hand, a composite non-AIDS-related endpoint, including major cardiovascular diseases, liver fibrosis/cirrhosis, and non-AIDS-related malignancies, were studied with multivariate Poisson regression models in 12 800 patients diagnosed with HIV infection from 1998 onwards while not yet treated with cART. During 18 646 person-years of follow-up, 203 non-AIDS-related events occurred. Compared with a CD4 count ≥ 500 cells/μL, adjusted relative risks (RRs) for the composite endpoint were 4.71 [95% confidence interval (CI) 2.98-7.45] for a CD4 count < 200 cells/μL, 2.06 (95% CI 1.38-3.06) for a CD4 count of 200-349 cells/μL, and 1.19 (95% CI 0.82-1.74) for a CD4 count of 350-499 cells/μL. There was no evidence for an independent association with HIV RNA. Other important covariates were age [RR 1.40 (95% CI 1.31-1.49) per 5 years older], hepatitis B virus coinfection [RR 5.66 (95% CI 3.87-8.28)] and hepatitis C virus coinfection [RR 9.26 (95% CI 6.04-14.2)]. In persons not yet receiving cART, a more severe degree of immunodeficiency rather than higher HIV RNA levels appears to be associated with an increased risk of our composite non-AIDS-related endpoint. Larger studies are needed to address these associations for individual non-AIDS-related events. © 2015 British HIV Association.
    HIV Medicine 01/2015; · 3.45 Impact Factor
  • 20th International AIDS conference, Melbourne, Australia; 07/2014
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    ABSTRACT: Document progress in HIV-treatment in the Netherlands since 1996 by reviewing changing patterns of cART use and relating those to trends in patients' short-term clinical outcomes between 1996 and 2010. 1996-2010 data from 10,278 patients in the Dutch ATHENA national observational cohort were analysed. The annual number of patients starting a type of regimen was quantified. Trends in the following outcomes were described: i) recovery of 150 CD4 cells/mm(3) within 12 months of starting cART; ii) achieving viral load (VL) suppression ≤1,000 copies/ml within 12 months of starting cART; iii) switching from first-line to second-line regimen within three years of starting treatment; and iv) all-cause mortality rate per 100 person-years within three years of starting treatment. Between 1996 and 2010, first-line regimens changed from lamivudine/zidovudine-based or lamivudine/stavudine-based regimens with unboosted-PIs to tenofovir with either emtricitabine or lamivudine with NNRTIs. Mortality rates did not change significantly over time. VL suppression and CD4 recovery improved over time, and the incidence of switching due to virological failure and toxicity more than halved between 1996 and 2010. These effects appear to be related to the use of new regimens rather than improvements in clinical care. The use of first-line cART in the Netherlands closely follows changes in guidelines, to the benefit of patients. While there was no significant improvement in mortality, newer drugs with better tolerability and simpler dosing resulted in improved immunological and virological recovery and reduced incidences of switching due to toxicity and virological failure.
    PLoS ONE 09/2013; 8(9):e76071. · 3.53 Impact Factor
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    ABSTRACT: Background: We estimated the impact of loss to follow-up (LTFU) on the mortality rate amongst HIV-1 infected patients in Curaçao. Methods: A total of 214 therapy-naïve HIV-1 infected patients aged 15 years or older upon entering into HIV care between January 2005 and July 2009 were included. Persons who discontinued follow-up for more than 365 days were defined as LTFU and traced with the aim of registering their vital status. If no personal contact could be made, data were matched with the Curaçao National Death Registry. Mortality rates were estimated before and after starting combined antireteroviral therapy (cART). We used log-rank tests to compare survival rates amongst patients LTFU and patients who experienced continuous follow-up. Results: Pre-cART mortality in patients LTFU was similar to pre-cART mortality in those with continuous follow-up (p=0.79). All pre-cART deaths occurred within 6 months after entry. Late diagnosis was predictive for a shorter time to death after entry. Adjusting for those who were LTFU, the mortality rate after starting cART increased from 4.3 to 5.5 per 100 person years of observation (p=0.06). Mortality after starting cART was highest in the first 2 months after starting cART, especially for those who had late disease stage. Mortality rates were lower in patients with continuous follow-up compared to LTFUs (p<0.001). Conclusion: Mortality rates in HIV-1 infected patients who have started cART in Curaçao are underestimated as a result of inefficient patient administration combined with people starting cART at very late disease stage. Monitoring HIV treatment could help reducing the risk of LTFU and may improve the effect of treatment.
    AIDS research and human retroviruses 08/2013; · 2.18 Impact Factor
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    ABSTRACT: The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org).
    International Journal of Epidemiology 04/2013; · 9.20 Impact Factor
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    ABSTRACT: Abstract Retention in care is one of the major challenges to scaling up and maximizing the effectiveness of combination antiretroviral therapy (cART). High attrition rates have been reported in the Caribbean region, varying from 6% to 23%. We studied the incidence of and risk factors for intermittent care in a cohort of adult HIV-1-positive patients, who entered into care in Curaçao between January 2005 and July 2009. A total of 214 therapy-naïve HIV-1-infected patients aged 15 years or older, entered HIV care between January 2005 and July 2009. Intermittent care was defined as at least one period of 365 days or longer in which there was no HIV care contact in Curaçao. Cox regression models were used to identify characteristics associated with time to intermittent care. In all, 203 (95%) patients could be classified as having intermittent or continuous care. The incidence of intermittent care before starting cART was 25.4 per 100 person years observation (PYO), whilst it was 6.1 per 100 PYO after starting cART. Being born outside Curaçao was associated with intermittent care before and after starting cART. Time from diagnosis to entry into care was an independent predictor for intermittent care before starting cART. Younger age was independently associated with intermittent care after starting cART. Half of the patients returned to care after intermitting care. Upon returning to care, median CD4 count was 264 cells/mm(3) (IQR, 189-401) for those who intermitted care before starting cART, and 146 cells/mm(3) (IQR, 73-436) in those who intermitted care after starting cART. In conclusion, the incidence of intermitting care is high in Curaçao, especially before starting cART, and intermitting care before starting cART is an independent predictor for starting cART late.
    AIDS Care 02/2013; · 1.60 Impact Factor
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    ABSTRACT: BACKGROUND:: In HIV-negative patients radiotherapy (RT) decreases CD4T-cell counts. We studied the effects of RT in HIV-1 positive patients. METHODS:: HIV-1 positive patients with a subsequent diagnosis of a solid tumor were selected from the Dutch national observational HIV cohort (ATHENA). Patients were grouped according to whether they had received RT or not. Primary endpoint of the study was time from baseline to reaching CD4 cell counts higher than those at baseline. Kaplan-Meier estimates of the percentage of patients reaching the endpoint were calculated. RESULTS:: 90 patients were included of which 36 received RT and 54 not. Median duration of RT was 46 (IQR 30-63) days. Median first CD4 cell count after stopping RT was 150 (IQR 30-270) x10/L lower compared with baseline. In 13 of the 36 patients receiving RT, CD4 cell counts recovered to baseline, after a median of 469 (IQR 345-595) days. In 35 of the 54 patients without RT CD4 cell count recovered to baseline or higher, after a median of 112 (IQR 42-182) days. After 3 years, in 39% of patients who had RT compared to 71% of patients without RT CD4 cell counts recovered to baseline or higher (p<0.0001). In a Cox regression adjusted for potential confounders, RT was associated with a longer (HR 0.29 (95% CI 0.13 - 0.63), and cART use with a shorter time to return to baseline (HR 2.46 (95% CI 1.11-5.48). CONCLUSION:: RT resulted in a significant and prolonged decrease in CD4 cell counts.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2013; · 4.39 Impact Factor
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    ABSTRACT: The emergence of CXCR4-using HIV variants (X4-HIV) is associated with accelerated disease progression in the absence of antiretroviral therapy. However, the effect of X4-HIV variants on the treatment response remains unclear. Here we determined whether the presence of X4-HIV variants influenced the time to undetectable viral load and CD4+ T cell reconstitution after initiation of cART in 732 patients. The presence of X4-HIV variants was determined by MT-2 assay prior to cART initiation and viral load and CD4+ T cell counts were analyzed every 3 to 6 months during a three year follow-up period. Kaplan-Meier and Cox proportional hazard analyses were performed to compare time to viral suppression and the absolute CD4+ T cell counts and increases in CD4+ T cell counts during follow-up were compared for patients with and without X4-HIV at start of cART. Patients harboring X4-HIV variants at baseline showed a delay in time to achieve viral suppression below the viral load detection limit. This delay in viral suppression was independently associated with high viral load and the presence of X4-HIV variants. Furthermore, the absolute CD4+ T cell counts were significantly lower in patients harboring X4-HIV variants at all time points during follow-up. However, no differences were observed in the increase in absolute CD4+ T cell numbers after treatment initiation, indicating that the reconstitution of CD4+ T cells is independent of the presence of X4-HIV variants. The emergence of X4-HIV has been associated with an accelerated CD4+ T cell decline during the natural course of infection and therefore, patients who develop X4-HIV variants may benefit from earlier treatment initiation in order to obtain faster reconstitution of the CD4+ T cell population to normal levels.
    PLoS ONE 01/2013; 8(10):e76255. · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVE:: HIV-associated Pneumocystis jirovecii pneumonia (PJP) remains one of the commonest opportunistic infections in Western countries. Although it has been suggested that racial differences in PJP incidence exist, early studies report conflicting results. This study aims to investigate differences in PJP incidence in a developed country among patients originating from sub-Saharan Africa compared to other regions of origin. DESIGN AND METHODS:: A retrospective observational cohort study was performed among 13,844 HIV-infected patients from the Dutch ATHENA cohort. The main outcome measure was occurrence of PJP. RESULTS:: A total number of 1,055 PJP infections were diagnosed. Patients originating from sub-Saharan Africa had a significantly lower risk for having PJP at time of HIV diagnosis after adjustment for confounders compared to patients from Western origin (Western Europe, Australia and New Zealand; adjusted odds ratio (aOR) 0.21 (95% CI 0.15-0.29)). Other factors associated with higher PJP risk were increasing age (aOR 1.01 per year (95% CI 1.00-1.02)), a low CD4 count at HIV diagnosis (CD4 <50 versus >350 cells/mm aOR 123.3 (95% CI 77.8-195.5)) and a high plasma HIV-RNA (>100,000 copies/μl) at HIV diagnosis (aOR 1.41 (95% CI 1.19-1.66)). Moreover, a clearly lower risk for PJP acquisition later during follow-up was observed among Sub-Saharan Africans versus Western patients (aHR 0.60 (95% CI 0.39-0.90)). CONCLUSION:: Among HIV-infected patients living in the Netherlands, PJP occurrence is substantially lower in patients originating from sub-Saharan Africa, as compared to Western patients. Differences in genetic susceptibility may partially explain the lower PJP incidence in these patients.
    AIDS (London, England) 12/2012; · 6.56 Impact Factor
  • Netherlands Conference on HIV Pathogenesis, Epidemiology, Prevention and Treatment, Amsterdam, The Netherlands; 11/2012
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    AIDS (London, England) 09/2012; 26(15):1974-1977. · 6.56 Impact Factor
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    ABSTRACT: BACKGROUND: New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. METHODOLOGY/PRINCIPAL FINDINGS: The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995-1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. CONCLUSIONS/SIGNIFICANCE: The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.
    PLoS ONE 09/2012; 7(9):e44819. · 3.53 Impact Factor
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    ABSTRACT: Background We assessed whether quadruple or triple-class therapy for the initial treatment of HIV-1 infection provides a virological benefit over standard triple therapy in patients with a very high plasma viraemia.Design National observational HIV cohort in the Netherlands.Methods Inclusion criteria were age ≥18 years, treatment-naïve, plasma viral load (pVL) ≥500.000 copies/ml and initiation of quadruple or triple therapy between 2001-2011. Time to viral suppression, defined as pVL <50 c/ml, was compared between the two groups using Kaplan-Meier plots and multivariate Cox regression analysis.Results 675 patients were included: 125 (19%) initiated quadruple and 550 (81%) triple therapy. Median pVL was 5.9 (IQR 5.8-6.1) log(10) c/ml in both groups (P=0.49). 22 (18%) patients on quadruple and 63 (12%) on triple therapy interrupted the treatment regimen because of drug-related toxicity (P=0.06). Median time to viral suppression was 5.8 (IQR 4.6-7.9) and 6.0 (4.0-9.4) months in the patients on quadruple and triple therapy (log rank, P=0.42). In the adjusted Cox analysis, quadruple therapy was not associated with time to viral suppression (HR 1.07 (95% CI 0.86-1.33), P=0.53). Similar results were seen when comparing triple- versus dual-class therapy (n=72 vs. n=601, respectively).Conclusions Initial quadruple or triple-class therapy was equally effective as standard triple therapy in the suppression of HIV-1 in treatment-naïve patients with very high viraemia and did not result in a faster pVL decline, but did expose patients to additional toxicity.
    Antiviral therapy 08/2012; · 3.14 Impact Factor
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    ABSTRACT: Changes in risk behaviour among men who have sex with men (MSM) in the Netherlands were estimated by fitting a mathematical model to annual HIV and AIDS diagnoses in the period 1980-2009 and, independently, from rates of unprotected anal intercourse in a prospective cohort study in Amsterdam. The agreement between the two approaches was very good, confirming that in terms of incidence, increasing risk behaviour between MSM is offsetting benefits offered by enhanced testing and treatment.
    AIDS (London, England) 07/2012; 26(14):1840-3. · 6.56 Impact Factor
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    ABSTRACT: : To quantify the performance of existing first-line and second-line combination antiretroviral therapy (cART) regimens on patient's clinical outcomes in the Netherlands using ATHENA data and to evaluate the potential for new drug regimens to improve patient's clinical outcomes using a data-based mathematical model. : We analysed data from 3995 patients from the Dutch ATHENA national observational cohort between 2000 and 2010. We quantified the main drug-related reasons for switching from first-line and second-line cART, classified as toxicity, simplification/new medication becoming available, virological failure, or other reasons. We developed a deterministic model describing HIV infection and treatment in the Netherlands parameterized on the basis of these data. The model simulated how a new drug regimen, with either improved toxicity or virological failure profile, could impact on patient's clinical outcomes. : The main reason for switching current first-line and second-line regimens was toxicity, accounting for around 50% of switching from first-line and from second-line cART. The model found that a new drug regimen with increased tolerability profile could have the highest potential impact on patient's outcomes, especially as a first-line treatment. A new first-line drug regimen with improved tolerability could increase the time patients spend on first-line cART, decrease their risk of switching from first-line cART and thus simplify patient management. : New drug regimens with improved toxicity profiles could have the greatest impact on patient outcomes and simplify patient management in the Netherlands.
    AIDS (London, England) 06/2012; 26(15):1953-9. · 6.56 Impact Factor
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    ABSTRACT: OBJECTIVES: The aim of the study was to compare health-related quality of life (HRQL) over 96 weeks in patients receiving no treatment or 24 or 60 weeks of combination antiretroviral therapy (cART) during primary HIV-1 infection (PHI). METHODS: A multicentre prospective cohort study of PHI patients, with an embedded randomized trial, was carried out. HRQL was assessed with the Medical Outcomes Study Health Survey for HIV (MOS-HIV) and a symptom checklist administered at weeks 0, 8, 24, 36, 48, 60, 72, 84 and 96. Mixed linear models were used for the analysis of differences in HRQL among the three groups. RESULTS: A total of 112 patients were included in the study: 28 received no treatment, 45 received 24 weeks of cART and 39 received 60 weeks of cART. Over 96 weeks of follow-up, the groups receiving 24 and 60 weeks of cART had better cognitive functioning than the no-treatment group (P = 0.005). Patients receiving 60 weeks of cART had less pain (P = 0.004), better role functioning (P = 0.001), better physical functioning (P = 0.02) and a better physical health summary score (P = 0.006) than the groups receiving no treatment or 24 weeks of cART. Mental health was better in patients receiving 24 weeks of cART than in patients in the no-treatment group or the group receiving 60 weeks of cART (P = 0.02). At week 8, patients in the groups receiving 24 and 60 weeks of cART reported more nausea (P = 0.002), diarrhoea (P < 0.001), abdominal pain (P = 0.02), stomach pain (P = 0.049) and dizziness (P = 0.01) than those in the no-treatment group. These differences had disappeared by week 24. CONCLUSIONS: Temporary cART during PHI had a significant positive impact on patients' HRQL as compared with no treatment, despite the initial, short-term occurrence of more physical symptoms, probably related to drug toxicity.
    HIV Medicine 04/2012; 13(10):630-635. · 3.45 Impact Factor
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    ABSTRACT: Several studies reported an association between immunodeficiency and non-AIDS-defining diseases. We investigated whether nonstructured treatment interruptions and episodes of viremia during suppressive combination antiretroviral therapy were independently associated with non-AIDS diseases. Six thousand four hundred forty patients with viral suppression (<50 copies/mL) within 48 weeks of starting combination antiretroviral therapy were selected from the Dutch ATHENA cohort. In proportional hazards models, associations between treatment interruptions, viral suppression, low-level (50-400 copies/mL), and high-level viremia (>400), and serious non-AIDS diseases (cardiovascular disease, chronic renal failure, liver fibrosis/cirrhosis) were investigated by including time-updated cumulative exposure to either viremia and interruptions or HIV RNA >400 copies per milliliter. During 24,603 person-years, of which 88.5% occurred during viral suppression, 102 patients developed cardiovascular disease, 54 chronic renal failure, and 70 liver fibrosis/cirrhosis. Overall incidence of non-AIDS diseases ranged from 1.41 (95% confidence interval: 0.73 to 2.46) per 100 person-years for CD4 counts <200 to 0.71 (0.49 to 1.00) for CD4 ≥500 cells per cubic millimeter. Compared with viral suppression, high-level viremia was associated only with cardiovascular disease (relative hazard: 1.37, 1.04 to 1.81 per year longer), whereas interruptions and low-level viremia were not associated with non-AIDS diseases. Relative hazards for cumulative exposure to RNA >400 versus ≤400 copies per milliliter were 1.32 (1.01 to 1.73) for cardiovascular disease, 1.13 (0.66 to 1.92) for renal failure, and 0.86 (0.51 to 1.44) for fibrosis/cirrhosis. Lower CD4 counts are associated with increased risk of non-AIDS diseases, whereas high-level viremia seems to be independently associated with cardiovascular disease. However, the power to detect associations with viremia or interruptions may have been limited as most events occurred during viral suppression.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2012; 60(3):265-72. · 4.39 Impact Factor

Publication Stats

9k Citations
1,451.29 Total Impact Points

Institutions

  • 2009–2013
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 2001–2013
    • Imperial College London
      • Department of Infectious Disease Epidemiology
      London, ENG, United Kingdom
  • 2011
    • National Institute of Allergy and Infectious Diseases
      Maryland, United States
  • 1989–2011
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Internal Medicine
      • • Department of Human Retrovirology
      • • Department of Virology
      Amsterdamo, North Holland, Netherlands
  • 1986–2010
    • University of Amsterdam
      • • Faculty of Medicine AMC
      • • Department of Internal Medicine
      • • Department of Clinical Epidemiology and Biostatistics
      • • Central Laboratory of the Netherlands Red Cross Blood Transfusion Service
      Amsterdam, North Holland, Netherlands
  • 2002
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1989–2001
    • Gezond Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2000
    • University of Oxford
      • Department of Zoology
      Oxford, England, United Kingdom
  • 1998
    • Slotervaartziekenhuis
      Amsterdamo, North Holland, Netherlands
  • 1996–1998
    • Hong Kong Red Cross Blood Transfusion Service
      Hong Kong, Hong Kong
  • 1990
    • Gemeentelijke Geneeskundige en Gezondheidsdienst
      Utrecht, Utrecht, Netherlands