Colette Smit

Imperial College London, London, ENG, United Kingdom

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Publications (24)100.55 Total impact

  • Article: Episodes of HIV viremia and the risk of non-AIDS diseases in patients on suppressive antiretroviral therapy.
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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. · 4.43 Impact Factor
  • Article: Hcv coinfection, an important risk factor for hepatotoxicity in pregnant women starting antiretroviral therapy.
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    ABSTRACT: This retrospective cohort study evaluated the risk of hepatotoxicity in HIV-1 positive pregnant and non-pregnant women starting combined ART. Data were used from the ATHENA observational cohort. The study population consisted of HIV-1 infected, therapy naïve, pregnant and non-pregnant women, followed between January 1997 and February 2008. Demographic, treatment and pregnancy related data were collected. Risk of hepatotoxicity was determined using univariate and multivariate logistic regression. Analyses were adjusted for age, region of origin, baseline HIV-RNA levels and CD4 cell counts, cART regimen and hepatitis B and C coinfection. ALT and AST values of more than 5 times ULN were considered as hepatotoxicity. Four-hundred and twenty-five pregnant and 1121 non-pregnant women were included. Independent risk factors of hepatotoxicity in all women were the presence of detectable HCV RNA (OR 5.48, 95% CI 2.25-13.38, p<0.001) and NVP use (OR 2.63, 95% CI 1.54-4.55, p<0.001). Stratified for pregnancy, the adjusted risk of hepatotoxicity was significantly associated with HCV coinfection only during pregnancy (OR 23.53, 95% CI 4.69-118.01, p<0.001). NVP use is related to hepatotoxicity in pregnant (OR 5.26, 95% CI 1.61-16.67, p<0.005) as well as in non-pregnant women (OR 2.13, 95% CI 1.11-4.00, p=0.02). HCV coinfection and NVP use are associated with a higher risk of cART induced hepatotoxicity in pregnant women.
    The Journal of infection 12/2011; 64(4):409-16. · 4.13 Impact Factor
  • Article: Antenatal screening for HIV, hepatitis B and syphilis in the Netherlands is effective.
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    ABSTRACT: A screening programme for pregnant women has been in place since the 1950s in the Netherlands. In 2004 universal HIV screening according to opting out was implemented. Here, we describe the evaluation of the effectiveness of antenatal screening in the Netherlands for 2006-2008 for HIV, hepatitis B virus (HBV) and syphilis in preventing mother-to-child transmission, by using various data sources. The results of antenatal screening (2006-2008) were compared with data from pregnant women and newborns from other data sources. Each year, around 185,000 pregnant women were screened for HIV, HBV and syphilis. Refusal rates for the screening tests were low, and were highest (0.2%) for HIV. The estimated annual prevalence of HIV among pregnant women was 0.05%.Prior to the introduction of screening, 5-10 children were born with HIV annually After the introduction of screening in 2004, only 4 children were born with HIV (an average of 1 per year). Two of these mothers had become pregnant prior to 2004; the third mother was HIV negative at screening and probably became infected after screening; the fourth mother's background was unknown. Congenital syphilis was diagnosed in fewer than 5 newborns annually and 5 children were infected with HBV. In 3 of these, the mothers were HBeAg positive (a marker for high infectivity). We estimated that 5-10 HIV, 50-75 HBV and 10 syphilis cases in newborns had been prevented annually as a result of screening. The screening programme was effective in detecting HIV, HBV and syphilis in pregnant women and in preventing transmission to the child. Since the introduction of the HIV screening the number of children born with HIV has fallen dramatically. PREVIOUS PUBLICATION: [Translation from: 'Prenatale screening op hiv, hepatitis B en syphilis in Nederland effectief', published in 'The Dutch Journal of Medicine ' (NTVG, in Dutch)].
    BMC Infectious Diseases 06/2011; 11:185. · 3.12 Impact Factor
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    Article: Immunodeficiency as a risk factor for non-AIDS-defining malignancies in HIV-1-infected patients receiving combination antiretroviral therapy.
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    ABSTRACT: The aim of this study was to investigate the association between immunodeficiency, viremia, and non-AIDS-defining malignancies (NADM). Patients starting combination antiretroviral therapy (cART) as of 1 January 1996 were selected from the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. In Cox models, risk factors for NADM were investigated. These included age, sex, transmission route, smoking, alcohol abuse, prior AIDS diagnosis, duration of exposure to cART, and estimated duration of human immunodeficiency virus infection. CD4+ cell count and viral load (VL) were considered as time-updated variables and as measures of cumulative exposure to CD4+ cell counts of < 200, < 350, or < 500 cells/mm³ and detectable VL >50, >400, and >1000 copies/mL, respectively. In a cohort of 11,459 patients, 236 NADMs were diagnosed; 102 were caused by infection, and 134 were attributable to other causes. Median CD4+ cell count at NADM diagnosis was 340 cells/mm³ (range, 210-540 cells/mm³). Median time to first NADM after starting cART was 5.0 years (range, 2.2-8.2 years). In multivariate models, cumulative exposure to CD4+ cell counts < 200 cells/mm³ remained significant (hazard ratio [HR], 1.12; range, 1.03-1.22) for each additional year of exposure. In stratified analyses, cumulative exposure to CD4+ cell counts < 200 cells/mm³ was associated with malignancies possibly caused by infection (HR, 1.16; range, 1.03-1.31]) but was not associated with other types of cancers. No significant effect of viremia was seen in either type of cancer. Cumulative exposure to CD4+ cell counts < 200 cells/mm³ during cART was associated with an increased risk of infection-related non-AIDS-defining malignancies.
    Clinical Infectious Diseases 06/2011; 52(12):1458-65. · 9.15 Impact Factor
  • Article: Lower mortality and earlier start of combination antiretroviral therapy in patients tested repeatedly for HIV than in those with a positive first test.
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    ABSTRACT: Early diagnosis of HIV-1 infection will probably beneficially impact onward transmission and life expectancy. We compared mortality rates and CD4 cell counts at start of combination antiretroviral therapy (cART) in patients with different frequencies of diagnostic testing for HIV. Patients infected with HIV-1 through sexual contact and in follow-up anytime from 2004 through 2008 were selected from the AIDS Therapy Evaluation in the Netherlands national observational HIV cohort and stratified into three groups: patients without a prior negative HIV antibody test (i.e., with a positive first-test result); patients with 1-2 years between the last negative and first positive test; and patients with less than 1 year between tests. Outcome measures were mortality from 2004 through 2008 and CD4 cell count at cART initiation. Of 5494 patients, the mortality rate was highest among the 4067 patients with a positive first test (1.33/100 person-years) and the adjusted relative risk of mortality was 0.50 in 561 patients with tests 1-2 years apart (P = 0.04 compared to patients with a positive first test) and 0.49 (P = 0.02) when tests were less than 1 year apart (n = 866). In patients with a positive first test, 48% had CD4 cell counts less than 200 cells/μl at cART initiation; this proportion was 23-26% in the two groups of repeatedly tested patients (adjusted odds ratio compared to patients with a positive first test 0.43 and 0.37, respectively; both P < 0.0001). Frequent repeated testing for HIV may improve the rate of timely diagnosis and treatment, thereby preventing disease progression.
    AIDS (London, England) 02/2011; 25(6):813-8. · 4.91 Impact Factor
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    Article: Estimating the risk of HIV transmission from homosexual men receiving treatment to their HIV-uninfected partners.
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    ABSTRACT: To determine how the risk of HIV transmission from homosexual men receiving antiretroviral treatment is related to patterns of patient monitoring and condom use. A stochastic mathematical simulation model was developed of cohorts of men in the Netherlands who have sex with men (MSM), defining the parameters of the model using observational cohort data. The model incorporates viral load trends during first-line treatment, patient monitoring and different scenarios for the way in which condom use may depend on recent viral load measurements. The model does not include the effect of sexually transmitted infections on HIV transmission. For MSM receiving treatment, the risk of transmitting HIV to their long-term partner is 22% (uncertainty interval: 9-37%) if condoms are never used. With incomplete use (in 30% of sex acts) the risk is reduced slightly, to 17% (7-29%). However, the risk is as low as 3% (0.2-8%) when men receiving treatment use condoms only 6 months beyond their last undetectable viral load measurement. The risk is further reduced when 3 months is the time period beyond which condoms are used. When condom use by HIV-infected men receiving combination treatment with antiretroviral agents is based on their last viral load measurement, the transmission risk is much lower than with incomplete condom use. The key message for patients is that although always using condoms during treatment is the best way to protect partners from the risk of HIV transmission, when such use cannot be achieved, the second best strategy is to use condoms whenever the last undetectable viral load was measured more than 3 months ago.
    Sexually transmitted infections 02/2011; 87(1):17-21. · 2.18 Impact Factor
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    Article: Adherence to HIV therapeutic drug monitoring guidelines in The Netherlands.
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    ABSTRACT: Therapeutic drug monitoring (TDM) is recommended in several international HIV treatment guidelines. The adherence of clinicians to these recommendations is unknown. The authors evaluated the adherence to the Dutch TDM guideline of 2005. From the ATHENA cohort study, three scenarios were selected for which the guideline recommended TDM: 1) start of a combination of lopinavir/ritonavir + efavirenz or nevirapine (drug-drug interaction); 2) start of efavirenz (routine TDM); and 3) use of nelfinavir during pregnancy. For each scenario, we determined the proportion of patients for whom TDM was performed. Multivariable logistic regression modeling was used to identify determinants for the use of TDM. The adherence to the TDM guideline was 46.7% in patients who started lopinavir/ritonavir plus efavirenz or nevirapine; 9.5% for patients who started efavirenz; and 58.5% for patients who used nelfinavir during pregnancy. Patients treated in clinics that had a TDM assay available locally and patients treated in academic clinics were more likely to receive TDM. A higher baseline HIV viral load was another significant predictor for the performing TDM. The adherence of clinicians to the Dutch TDM guidelines varied from low to moderate for the three investigated TDM scenarios. This study identifies several determinants for the use of TDM, which may be useful information for those responsible for generating TDM guidelines.
    Therapeutic drug monitoring 02/2011; 33(1):32-9. · 2.43 Impact Factor
  • Article: The comparison of the performance of two screening strategies identifying newly-diagnosed HIV during pregnancy.
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    ABSTRACT: In the Netherlands, a non-selective opt-out instead of a selective opt-in antenatal HIV screening strategy was implemented in 2004. In case of infection, screening was followed by prevention of mother-to-child-transmission (PMTCT). We compared the performance of the two strategies in terms of detection of new cases of HIV and vertical transmission. HIV-infected pregnant women were identified retrospectively from the Dutch HIV cohort ATHENA January 2000 to January 2008. Apart from demographic, virological and immunological data, the date of HIV infection in relation to the index pregnancy was established. Separately, all infants diagnosed with HIV born following implementation of the screening program were identified by a questionnaire via the paediatric HIV centres. 162/481 (33.7%) HIV-positive pregnant women were diagnosed with HIV before 2004 and 172/214 (80.3%) after January 2004. Multivariate analysis showed an 8-fold (95% confidence interval 5.47-11.87) increase in the odds of HIV detection during pregnancy after the national introduction of the opt-out strategy. Still, three children born during a 5-year period after July 2004 were infected due to de novo infection in pregnancy. Implementation of a nation-wide screening strategy based upon non-selective opt-out screening followed by effective PMTCT appeared to detect more HIV-infected women for the first time in pregnancy and to reduce vertical transmission of HIV substantially. Nonetheless, still few children are infected because of maternal infection after the first trimester. We propose the introduction of partner screening on HIV as part of the antenatal screening strategy.
    The European Journal of Public Health 11/2010; 21(5):632-7. · 2.73 Impact Factor
  • Article: Clinical significance of transient HIV type-1 viraemia and treatment interruptions during suppressive antiretroviral treatment.
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    ABSTRACT: Transient episodes of HIV type-1 viraemia are frequently observed in patients on suppressive combination antiretroviral therapy (cART). We studied the effect of such episodes and of treatment interruptions on clinical outcome and immunological response. A total of 3,321 patients from the ATHENA cohort had virological suppression (HIV type-1 RNA<50 copies/ml) after 24 weeks of cART. The association between subsequent episodes of treatment interruptions, viral suppression, low-level (50-400 copies/ml) and high-level (>400 copies/ml) viraemia and the outcomes death, AIDS or immunological response (CD4(+) T-cell count increase > or =50% from 24 weeks) was studied with Poisson regression models, including either time-updated cumulative follow-up, time spent per type of episode or modelling episodes as binary status indicators. During 11,165 person-years of follow-up, 88 patients died, 111 developed AIDS and 2,019 had an immunological response. Longer follow-up time in treatment interruptions increased the risk of AIDS (relative risk [RR] 8.07, 95% confidence interval [CI] 3.98-16.4 per year longer) and impaired immunological response (RR 0.22, 95% CI 0.12-0.41). High-level viraemia was only associated with immunological response (RR 0.55, 95% CI 0.40-0.74), whereas low-level viraemia was not associated with any of the three outcomes. Status indicator models gave similar results. When also including time-updated CD4(+) T-cell counts, the observed associations diminished. Treatment interruptions and high-level, but not low-level, viraemia are strongly associated with clinical outcome, mainly via their effect on CD4(+) T-cell counts.
    Antiviral therapy 01/2010; 15(4):555-62. · 3.16 Impact Factor
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    Article: Measuring the Quality of Data Collection in a Large Observational Cohort of HIV and AIDS.
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    ABSTRACT: The aim of this study was to examine the quality of data collection by studying the validity of collected data. Data were extracted from the clinic charts of two anonymous outpatients by 38 data collectors. A standard for the data to be collected was determined (168 items). The validity was measured by comparing the collected items with the standard; in this way, the percentages of the collected items that were 'correct' could be calculated. The percentage 'correct' was higher for clinic chart 1 (mean: 83% correct, SD 7%) than for clinic chart 2 (mean: 78% correct, SD 8%). All categories contained incorrectly collected data. These data were divided into missing data, incorrect start-stop dates, and surplus collected data. Almost all start-stop dates would change into 'correct' if 'monthyear' was considered correct (instead of the standard 'daymonthyear'). Not all data collectors used specific protocols, and sources other than the written comments were not always checked. This study shows that a high proportion of data was correctly collected. However, the collection of start-stop dates was not optimal, and the collected data included surplus and missing data. Data collectors should be more knowledgeable about HIV disease and trained in the use of difficult protocols, so that they can better recognize what data to collect and how it should be collected. Among physicians, there should be more agreement about what information to record in the charts, to facilitate data extraction for data collectors.
    The Open AIDS Journal 01/2010; 4:96-102.
  • Article: Immune restoration and onset of new AIDS-defining events with combination antiretroviral therapy in HIV type-1-infected immigrants in the Netherlands.
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    ABSTRACT: We investigated differences in immune restoration and onset of new AIDS-defining events on combination antiretroviral therapy (cART) among HIV type-1 (HIV-1)-infected patients of different regional origin now living in the Netherlands. Treatment-naive adults reaching plasma viral load (pVL)<400 copies/ml within 9 months of starting cART were selected from the Netherlands ATHENA cohort. CD4(+) T-cell response on cART was determined over 7 years using mixed models. CD4(+) T-cell counts were excluded from the analyses at the first of two consecutive measurements of pVL≥400 copies/ml following prior suppression to <400 copies/ml. Multivariate analyses included gender, age, CD4(+) T-cell count and pVL prior to cART, hepatitis coinfection, HIV-1 transmission and region of origin (Western Europe/North America [WN], sub-Saharan Africa [SSA], Southeast Asia [SEA], Latin America/Caribbean [LAC] or other). For 6,057 selected patients (WN 3,947, SSA 989, SEA 237, LAC 695 and other 189), median follow-up was 3.2 years (WN 3.3, SSA 2.9, SEA 3.2, LAC 2.7 and other 2.7). CD4(+) T-cell increase in the first 6 months of cART was lower in males than females (-26 cells/mm(3); P<0.0001) and in patients from SSA compared with WN (-36 cells/mm(3); P<0.0001). Because men from SSA started with lower CD4(+) T-cell counts than men from WN, they continued to lag behind and had lower absolute CD4(+) T-cell counts after 7 years of cART. Furthermore, cumulative tuberculosis incidence after 7 years of cART was higher in SSA compared with WN (4.5% versus 0.5%, hazard ratio 5.08, 95% confidence interval 2.22-11.60). HIV-1-infected immigrants from SSA have blunted immune restoration on fully suppressive cART and should be identified at an earlier disease stage. Our results call for more intensive screening for both latent and active tuberculosis in these patients.
    Antiviral therapy 01/2010; 15(6):871-9. · 3.16 Impact Factor
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    Article: Health-related quality of life and survival among HIV-infected patients receiving highly active antiretroviral therapy: a study of patients in the AIDS Therapy Evaluation in the Netherlands (ATHENA) Cohort.
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    ABSTRACT: Previous studies have shown that health-related quality of life (HRQL) predicts survival in patients infected with human immunodeficiency virus (HIV). However, these studies predated the highly active antiretroviral therapy (HAART) era, included only a few patients receiving HAART, or had a limited duration of follow-up. This study investigates whether HRQL predicts survival among HIV-infected patients receiving HAART. HIV-infected patients participating in the focus group of the AIDS Therapy Evaluation in the Netherlands (ATHENA) study and starting or already receiving HAART completed the Medical Outcomes Study HIV Health Survey at study entry (1 May 1998 through 31 December 2000). The physical health summary (PHS) and mental health summary (MHS) scores were calculated. All-cause mortality was established at 31 March 2008. Kaplan-Meier analysis and Cox regression models were performed to predict survival. The median follow-up was 8.4 years. Sixty-six patients (11.8%) died during follow-up. We found a significant relation between quartiles of PHS and survival (P < .001, log-rank test). Of patients with a PHS, 26 (20%) died in quartile 1 (indicating worst HRQL), 17 (13%) died in quartile 2, 10 (8%) died in quartile 3, and 5 (4%) died in quartile 4 (indicating best HRQL) (P< .001). The prediction of PHS on survival was independent of other (clinical) parameters (P< .001). No relation was found between MHS and survival (P= .13). Patient-reported HRQL predicted survival among HIV-infected patients receiving HAART. This information could be highly useful for physicians in determining the prognosis of their patients.
    Clinical Infectious Diseases 12/2009; 50(2):255-63. · 9.15 Impact Factor
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    Article: Lymphogranuloma venereum proctitis in men who have sex with men is associated with anal enema use and high-risk behavior.
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    ABSTRACT: In the industrialized world, lymphogranuloma venereum proctitis (LGVP) has been reported only in men who have sex with men. Factors responsible for the outbreak remain to be elucidated. The goal of the present work was to elucidate risk factors associated with LGVP. The study design comprised a cross-sectional study including 32 men with LGVP and 93 men without LGVP (22 with gonorrheal proctitis, 30 with a non-LGV chlamydial proctitis, and 41 with proctitis of unknown etiology). Factors associated with LGVP were analyzed by (multinomial) logistic regression. Comparing men with LGVP with men without LGVP, factors significantly associated with higher risk of LGVP in multivariate analyses were as follows: anal enema use [odds ratio (OR): 7.8, 95% confidence interval (CI): 2.6-23.2], having sex on sex parties (OR: 5.7, 95% CI: 1.5-21.8), and having sex with human immunodeficiency virus-positive partners (OR: 3.2, 95% CI: 1.1-9.3). Evaluating the 4 proctitis groups separately in a multinomial logistic regression model, similar associations between anal enema use and LGVP were found. Men with non-LGV chlamydial proctitis showed less risk behavior than men with LGVP. No substantial difference in risk behavior was found, except for attending sex parties, between men with LGVP, and gonorrheal proctitis or proctitis of unknown etiology. Apart from men with LGVP, men with gonorrheal proctitis or proctitis of unknown etiology exhibit high risk behavior. Enema use seems to play a key role in transmission of LGVP, and needs further investigation.
    Sex Transm Dis 03/2008; 35(2):203-8. · 2.87 Impact Factor
  • Article: Risk of hepatitis-related mortality increased among hepatitis C virus/HIV-coinfected drug users compared with drug users infected only with hepatitis C virus: a 20-year prospective study.
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    ABSTRACT: Progression of liver-related disease is accelerated in individuals coinfected with HIV and hepatitis C virus (HCV). Because the life expectancy of HIV-infected drug users (DUs) improved after the widespread use of highly active antiretroviral therapy (HAART), HCV-related death is likely to become more important. To disentangle the effects of HCV and HIV, we compared the overall and cause-specific mortality between HCV/HIV-infected DUs and HCV-infected DUs and DUs without HCV or HIV, followed up between 1985 and 2006. A total of 1295 participants in the Amsterdam Cohort Study were included. Cause-specific hazard ratios (CHRs) were estimated for the eras before (<1997) and since HAART (> or =1997) within and among serologic groups. The risk of dying decreased for most causes of death > or =1997; this decrease was not the same for the different serologic groups. Among HCV/HIV-coinfected DUs, the risk of hepatitis/liver-related death did not substantially change over time (CHR = 0.87, 95% confidence interval [CI]: 0.21 to 3.58), whereas the risk of AIDS-related mortality decreased. Compared with DUs solely infected with HCV, HCV/HIV-coinfected DUs were at increased risk of dying from hepatitis/liver-related disease (CHR = 7.15, 95% CI: 1.98 to 25.8), other natural causes (CHR = 3.09, 95% CI: 1.41 to 6.79), and nonnatural causes (CHR = 2.30, 95% CI: 1.07 to 4.95) in the HAART era. HCV/HIV-coinfected DUs remain at increased risk of dying from hepatitis/liver-related death in the HAART era compared with HCV-monoinfected DUs. This risk did not change in HCV/HIV-coinfected DUs after HAART was introduced, suggesting that in the HAART era, HIV continues to accelerate HCV disease progression. Efforts should be made to establish effective treatment for HCV infection in HCV/HIV-coinfected individuals.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2008; 47(2):221-5. · 4.43 Impact Factor
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    Article: Late entry to HIV care limits the impact of anti-retroviral therapy in The Netherlands.
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    ABSTRACT: To explain differences in survival in the first three years of combination anti-retroviral therapy (cART) between HIV treatment centres in The Netherlands. We developed a mathematical simulation model, parameterised using data from the ATHENA cohort that describes patients entering care, being monitored and starting cART. Three scenarios were used to represent three treatment centres with widely varying mortality rates on cART that were differentiated by: (i) the distribution of CD4 counts of patients entering care; (ii) the age distribution of patients entering care; (iii) the average rate of monitoring the patients not on cART. At the level of the treatment centre, the fraction of Dutch MSM dying in the first three years of treatment ranged from 0% to 8%. The mathematical model captured the large variation in observed mortality between the three treatment centres. Manipulating the age-distribution of patients or the frequency of monitoring did not affect the model predictions. In contrast, when the same national average distribution of CD4 count at entry was used in all the scenarios, the variation in predicted mortality between all centres was diminished. Patients entering care with low CD4 counts appears to be the main source of variation in the mortality rates between Dutch treatment centres. Recruiting HIV-infected individuals to care earlier could lead to substantial improvements in cART outcomes. For example, if patients were to present with at least 400 CD4 cells/mm(3), as they do already in some centres, then our model predicts that the mortality in the first three years of cART could be reduced by approximately 20%.
    PLoS ONE 02/2008; 3(4):e1949. · 4.09 Impact Factor
  • Article: Lymphogranuloma Venereum Proctitis in Men Who Have Sex With Men Is Associated With Anal Enema Use and High-Risk Behavior
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    ABSTRACT: Objectives: In the industrialized world, lymphogranuloma venereum proctitis (LGVP) has been reported only in men who have sex with men. Factors responsible for the outbreak remain to be elucidated. GOAL: The goal of the present work was to elucidate risk factors associated with LGVP. Study Design: The study design comprised a cross-sectional study including 32 men with LGVP and 93 men without LGVP (22 with gonorrheal proctitis, 30 with a non-LGV chlamydial proctitis, and 41 with proctitis of unknown etiology). Factors associated with LGVP were analyzed by (multinomial) logistic regression. Results: Comparing men with LGVP with men without LGVP, factors significantly associated with higher risk of LGVP in multivariate analyses were as follows: anal enema use [odds ratio (OR): 7.8, 95% confidence interval (CI): 2.6-23.2], having sex on sex parties (OR: 5.7, 95% CI: 1.5-21.8), and having sex with human immunodeficiency virus-positive partners (OR: 3.2, 95% CI: 1.1-9.3). Evaluating the 4 proctitis groups separately in a multinomial logistic regression model, similar associations between anal enema use and LGVP were found. Men with non-LGV chlamydial proctitis showed less risk behavior than men with LGVP. No substantial difference in risk behavior was found, except for attending sex parties, between men with LGVP, and gonorrheal proctitis or proctitis of unknown etiology. Conclusions: Apart from men with LGVP, men with gonorrheal proctitis or proctitis of unknown etiology exhibit high risk behavior. Enema use seems to play a key role in transmission of LGVP, and needs further investigation.
    Sex Transm Dis 01/2008; 35(2):203-208. · 2.87 Impact Factor
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    Article: Full participation in harm reduction programmes is associated with decreased risk for human immunodeficiency virus and hepatitis C virus: evidence from the Amsterdam Cohort Studies among drug users.
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    ABSTRACT: To investigate the impact of harm-reduction programmes on HIV and hepatitis C virus (HCV) incidence among ever-injecting drug users (DU) from the Amsterdam Cohort Studies (ACS). The association between use of harm reduction and seroconversion for human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV) was evaluated using Poisson regression. A total of 714 DU were at risk for HIV and/or HCV during follow-up. Harm reduction was measured by combining its two most important components--methadone dose and needle exchange programme (NEP) use--and looking at five categories of participation, ranging from no participation (no methadone in the past 6 months, injecting drug use in the past 6 months and no use of NEP) to full participation (> or = 60 mg methadone/day and no current injecting or > or = 60 mg methadone/day and current injecting but all needles exchanged). Methadone dose or NEP use alone were not associated significantly with HIV or HCV seroconversion. However, with combination of these variables and after correction for possibly confounding variables, we found that full participation in a harm reduction programme (HRP) was associated with a lower risk of HIV and HCV infection in ever-injecting drug users (DU), compared to no participation [incidence rate ratio 0.43 (95% CI 0.21-0.87) and 0.36 (95% CI 0.13-1.03), respectively]. In conclusion, we found that full participation in HRP was associated with a lower incidence of HCV and HIV infection in ever-injecting DU, indicating that combined prevention measures--but not the use of NEP or methadone alone--might contribute to the reduction of the spread of these infections.
    Addiction 09/2007; 102(9):1454-62. · 4.31 Impact Factor
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    Article: Major decline of hepatitis C virus incidence rate over two decades in a cohort of drug users.
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    ABSTRACT: Injecting drug users (DU) are at high risk for hepatitis C virus (HCV) and HIV infections. To examine the prevalence and incidence of these infections over a 20-year period (1985-2005), the authors evaluated 1276 DU from the Amsterdam Cohort Studies who had been tested prospectively for HIV infection and retrospectively for HCV infection. To compare HCV and HIV incidences, a smooth trend was assumed for both curves over calendar time. Risk factors for HCV seroconversion were determined using Poisson regression. Among ever-injecting DU, the prevalence of HCV antibodies was 84.5% at study entry, and 30.9% were co-infected with HIV. Their yearly HCV incidence dropped from 27.5/100 person years (PY) in the 1980s to 2/100 PY in recent years. In multivariate analyses, ever-injecting DU who currently injected and borrowed needles were at increased risk of HCV seroconversion (incidence rate ratio 29.9, 95% CI 12.6, 70.9) compared to ever-injecting DU who did not currently inject. The risk of HCV seroconversion decreased over calendar time. The HCV incidence in ever-injecting DU was on average 4.4 times the HIV incidence, a pattern seen over the entire study period. The simultaneous decline of both HCV and HIV incidence probably results from reduced risk behavior at the population level.
    European Journal of Epidemiology 02/2007; 22(3):183-93. · 4.71 Impact Factor
  • Article: Rise in seroprevalence of herpes simplex virus type 1 among highly sexual active homosexual men and an increasing association between herpes simplex virus type 2 and HIV over time (1984-2003).
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    ABSTRACT: Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) are both highly prevalent. The rate of genital HSV-1 transmission is reportedly increasing over time. HSV-2 is considered to be an important risk factor for HIV transmission. We therefore studied changes in the HSV-1 and HSV-2 prevalence in a large cohort of men who have sex with men (MSM) over a 20-year time period. Among 1847 HIV-infected and HIV-uninfected MSM participating in the Amsterdam Cohort Studies, seroprevalence of HSV-1 and HSV-2 was determined and prevalence rate ratios (PRR) and 95% confidence intervals were calculated. Between 1984 and 2003 the HSV-1 and HSV-2 prevalence decreased among HIV-uninfected MSM (P < 0.001), but remained stable among HIV-infected MSM. HSV-1 prevalence increased among men with at least 200 sexual partners over lifetime (PRR: 1.49, P < 0.001). The association between HIV infection and HSV-2 became stronger over time (PRR: 3.45, P < 0.001). Seroprevalence of HSV-1 and HSV-2 remained high among HIV infected MSM from 1984 to 2003. The association of HIV and HSV-2 increased during the HIV epidemic. Since the proportion of sexual transmission of HSV-1 is rising, it is important to study the potential role of HSV-1 as risk factor for HIV acquisition.
    European Journal of Epidemiology 01/2007; 22(12):937-44. · 4.71 Impact Factor
  • Article: Decline in HIV incidence and injecting, but not in sexual risk behaviour, seen in drug users in Amsterdam: a 19-year prospective cohort study.
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    ABSTRACT: To study temporal changes in HIV incidence, HIV transmission routes, and both injecting and sexual risk behaviour in the open Amsterdam Cohort Study (ACS) among drug users. Initiated in 1985, the ACS enables us to study changes in trends since HAART became widespread in 1996. Person-time techniques were used to study the trend in HIV incidence among HIV-negative drug users. HIV transmission routes were determined using detailed standardised questionnaires. Trends in injecting and sexual risk behaviours were evaluated with a logistic regression model adjusted for correlations between visits of the same individual. The 1315 HIV-negative individuals, of whom 93 seroconverted for HIV, yielded 6970 HIV-negative person-years of follow-up. The HIV incidence was seven per 100 person-years in 1986 and varied between 0 and 0.5 per 100 person-years after 1999. The odds ratio was 15.6 (95% confidence interval, 2.6-94.6) for HIV transmission through unprotected heterosexual contact versus injecting after 1996 compared with the period before. Reports of both injecting and borrowing needles significantly declined over the period 1985-2004. Reports of sexual risk behaviour and sexually transmitted infections at follow-up visits decreased before 1996, but not after 1996. The HIV incidence among drug users in the ACS has declined since 1985. Accompanied by a reduction in injecting drug use and needle sharing, this decline occurred despite continued sexual risk behaviour. At present, new HIV seroconversions are related mainly to unprotected heterosexual contacts. Therefore, HIV prevention programmes for drug users should pay specific attention to the importance of safe sex practices.
    AIDS 09/2006; 20(13):1771-5. · 6.24 Impact Factor

Institutions

  • 2011
    • Imperial College London
      • Department of Infectious Disease Epidemiology
      London, ENG, United Kingdom
  • 2007–2011
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Obstetrics & Gynecology
      • • Department of Human Retrovirology
      Amsterdam, North Holland, Netherlands
    • Academic Medical Center (AMC)
      Amsterdam, North Holland, Netherlands
  • 2007–2010
    • Universiteit van Amsterdam
      • Faculty of Medicine AMC
      Amsterdam, North Holland, Netherlands
  • 2006
    • Gezond Amsterdam
      Amsterdam, North Holland, Netherlands
  • 2004–2006
    • Gemeentelijke Geneeskundige en Gezondheidsdienst
      Utrecht, Provincie Utrecht, Netherlands