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Abstract Background Partner notification (PN) among individuals newly diagnosed with HIV/STI is seen as a vital tool to identify others at risk of infection. However, hardly any data are available on the effectiveness of PN on HIV/STI transmission in the Netherlands. This study aims to fill this gap by assessing current PN practices, case-finding effectiveness, and determinants of being notified among men having sex with men (MSM) in the Netherlands. Methods Nurses from five STI centers participated in a prospective pilot study on PN outcomes (partners being: at risk, notifiable, notified, and tested) for HIV/STI, by completing a newly developed PN registration form (PN database). PN outcomes including case-finding effectiveness (number of newly diagnosed cases in partners/number of partners being tested) for HIV, syphilis, and gonorrhoea were studied among MSM. Furthermore, the national STI database was analyzed to identify determinants of being notified. The number of infections that remained undetected was estimated based on these two databases. Results In total 105 MSM, newly diagnosed with HIV/STI, reported 612 sexual partners at risk of whom 41% were notifiable and 31% were notified. Patient referral was the predominant PN method (90%). The overall case-finding percentage was 36% (HIV: 15-33%, gonorrhoea: 17-50% and syphilis: 4-11%). Case-finding percentages were lower in the national STI database: 21% (5%, 28%, 12%). Persons with one or more sexual partners, known HIV positives, and IDU were more likely to be notified to the STI clinic. Notified clients were more likely to have HIV/STI than unnotified clients (OR 1.7-2.5). Based on these two databases, an estimated 75 to 133 infections remained undetected (HIV: 12–90; gonorrhoea: 28–97; syphilis: 5–12 infections). Conclusions Partner notification among MSM in the Netherlands is suboptimal; an extensive number of STI/HIV infections remained undetected mainly due to unnotifiable partners. To enhance PN practices, combined and innovative PN interventions such as Internet-based PN will be implemented for hard-to-reach MSM and other risk groups.

Abstract Background Effectiveness of Chlamydia screening programs is determined by an adequate level of participation and the capturing of high-risk groups. This study aimed to evaluate the contribution of automated reminders by letter, email and short message service (SMS) on package request and sample return in an Internet-based Chlamydia screening among people aged 16 to 29 years in the Netherlands. Methods Individuals not responding to the invitation letter received a reminder letter after 1 month. Email- and SMS-reminders were sent to persons who did not return their sample. It was examined to what extent reminders enhanced the response rate (% of package requests) and participation rate (% of sample return). Sociodemographic and behavioural correlates of providing a cell phone number and participation after the reminder(s) were studied by logistic regression models. Results Of all respondents (screening round 1: 52,628, round 2: 41,729), 99% provided an email address and 72% a cell phone number. Forty-two percent of all package requests were made after the reminder letter. The proportion of invitees returning a sample increased significantly from 10% to 14% after email/SMS reminders (round 2: from 7% to 10%). Determinants of providing a cell-phone number were younger age (OR in 25-29 year olds versus 16-19 year olds = 0.8, 95%CI 0.8-0.9), non-Dutch (OR in Surinam/Antillean versus Dutch = 1.3, 95%CI 1.2-1.4, Turkish/Moroccan: 1.1, 95%CI 1.0-1.2, Sub Sahara African: 1.5, 95%CI 1.3-1.8, non-Western other 1.1, 95%CI 1.1-1.2), lower educational level (OR in high educational level versus low level = 0.8, 95%CI 0.7-0.9), no condom use during the last contact with a casual partner (OR no condom use versus condom use 1.2, 95%CI 1.1-1.3), younger age at first sexual contact (OR 19 years or older versus younger than 16: 0.7, 95%CI 0.6-0.8). Determinants for requesting a test-package after the reminder letter were male gender (OR female versus male 0.9 95%CI 0.8-0.9), non-Dutch (OR in Surinam/Antillean versus Dutch 1.3, 95%CI 1.2-1.4, Turkish/Moroccan: 1.4, 95%CI 1.3-1.5, Sub Sahara African: 1.4, 95%CI 1.2-1.5, non-Western other: 1.2, 95%CI 1.1-1.2), having a long-term steady partnership (long-term versus short-term.1.2 95%CI 1.1-1.3). Email/SMS reminders seem to have resulted in more men and people aged 25-29 years returning a sample. Conclusions Nearly all respondents (99.5%) were reachable by modern communication media. Response and participation rates increased significantly after the reminders. The reminder letters also seemed to result in reaching more people at risk. Incorporation of automated reminders in Internet-based (Chlamydia) screening programs is strongly recommended.

Abstract Background 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. Methods The results of antenatal screening (2006-2008) were compared with data from pregnant women and newborns from other data sources. Results 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. Conclusions 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)]

Abstract Background Implementing Chlamydia trachomatis screening in the Netherlands has been a point of debate for several years. The National Health Council advised against implementing nationwide screening until additional data collected from a pilot project in 2003 suggested that screening by risk profiles could be effective. A continuous increase in infections recorded in the national surveillance database affirmed the need for a more active approach. Here, we describe the rationale, design, and implementation of a Chlamydia screening demonstration programme. Methods A systematic, selective, internet-based Chlamydia screening programme started in April 2008. Letters are sent annually to all 16 to 29-year-old residents of Amsterdam, Rotterdam, and selected municipalities of South Limburg. The letters invite sexually active persons to login to http://www.chlamydiatest.nl with a personal code and to request a test kit. In the lower prevalence area of South Limburg, test kits can only be requested if the internet-based risk assessment exceeds a predefined value. Results We sent invitations to 261,025 people in the first round. One-fifth of the invitees requested a test kit, of whom 80% sent in a sample for testing. The overall positivity rate was 4.2%. Conclusions This programme advances Chlamydia control activities in the Netherlands. Insight into the feasibility, effectiveness, cost-effectiveness, and impact of this large-scale screening programme will determine whether the programme will be implemented nationally.

Abstract Background A selective, systematic, Internet-based, Chlamydia Screening Implementation for 16 to 29-year-old residents started in three regions in the Netherlands in April 2008: in the cities of Amsterdam and Rotterdam and a more rural region, South Limburg. This paper describes the evaluation design and discusses the implications of the findings from the first screening round for the analysis. The evaluation aims to determine the effects of screening on the population prevalence of Chlamydia trachomatis after multiple screening rounds. Methods A phased implementation or 'stepped wedge design' was applied by grouping neighbourhoods (hereafter: clusters) into three random, risk-stratified blocks (A, B and C) to allow for impact analyses over time and comparison of prevalences before and after one or two screening rounds. Repeated simulation of pre- and postscreening Chlamydia prevalences was used to predict the minimum detectable decline in prevalence. Real participation and positivity rates per region, block, and risk stratum (high, medium, and low community risk) from the 1st year of screening were used to substantiate predictions. Results The results of the 1st year show an overall participation rate of 16% of 261,025 invitees and a positivity rate of 4.2%, with significant differences between regions and blocks. Prediction by simulation methods adjusted with the first-round results indicate that the effect of screening (minimal detectable difference in prevalence) may reach significance levels only if at least a 15% decrease in the Chlamydia positivity rate in the cities and a 25% decrease in the rural region after screening can be reached, and pre- and postscreening differences between blocks need to be larger. Conclusions With the current participation rates, the minimal detectable decline of Chlamydia prevalence may reach our defined significance levels at the regional level after the second screening round, but will probably not be significant between blocks of the stepped wedge design. Evaluation will also include other aspects and prediction models to obtain rational advice about future Chlamydia screening in the Netherlands.

Abstract Background The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced. Results In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration. For Poland no significant migratory pathways were inferred. Conclusion Subtype B phylogeographies provide a new insight about the geographical distribution of viral lineages, as well as the significant pathways of virus dispersal across Europe, suggesting that intervention strategies should also address tourists, travellers and migrants.

BackgroundIn 2022 and 2023, a global outbreak of mpox affected mostly gay, bisexual and other men having sex with men (GBMSM). Outbreak control in the Netherlands included isolation, quarantine, post-exposure prophylaxis vaccination and primary preventive vaccination (PPV).AimWe describe the course of the outbreak, the vaccination programme, vaccine effectiveness (VE) of full vaccination against symptomatic disease, and trends in behaviour to generate hypotheses about factors that influenced the outbreak's decline.MethodsIn this observational study, we collected data from public health services on notified cases, number of PPV invitations and PPV doses administered. We calculated PPV uptake and coverage. Trends in behavioural data of GBMSM visiting sexual health centres were analysed for all consultations in 2022. We estimated VE using the screening method.ResultsUntil 31 December 2023, 1,294 mpox cases were reported. The outbreak peaked in early July 2022 and then declined sharply. PPV started on 25 July 2022; in total 29,851 doses were administered, 45.8% received at least one dose, 35.4% were fully vaccinated. The estimated VE was 68.2% (95% CI 4.3-89.5%). We did not observe an evident decrease in high-risk behaviour.DiscussionIt is unlikely that PPV was a driver of the outbreak's decline, as incidence started to decline well before the start of the PPV programme. The possible impact of behavioural change could not be demonstrated with the available indicators, however, the data had limitations, hampering interpretation. We hypothesise that infection-induced immunity in high-risk groups was an important factor explaining the decline.

In August 2021, a man who has sex with men was diagnosed with HIV-1 infection despite using event-driven pre-exposure prophylaxis for over 2 years with self-reported excellent adherence. Sequencing identified resistance-associated mutations (RAM) M184V and K65R, conferring resistance to emtricitabine and tenofovir, and RAM V108I and E138A. Background RAM prevalence was two of 164 (1.2%) new HIV diagnoses in Amsterdam (2017-19). We reiterate the need for frequent HIV testing among PrEP users and additional testing in case of symptoms.

Background: Women having a termination of pregnancy (TOP) have higher rates of Chlamydia trachomatis (CT) than the general population. In this study, we explored CT treatment and prevention in Dutch TOP clinics in comparison to that provided in Great Britain (GB)., Methods: A qualitative study including 14 semi-structured interviews with health care professionals (HCPs) in TOP clinics (the Netherlands: 9, GB: 5). Interviews were recorded, transcribed, and analysed by thematic content analysis., Results: Prophylactic treatment with azithromycin is routinely prescribed after surgical TOP, but not after medical TOP ('abortion pill'). Sexually transmitted infections (STI) tests are offered to clients who are considered at high risk of having STI. Uptake varies according to health insurance coverage of STI testing. Some Dutch clinics are able to provide free testing for women under 25 years of age. Sexual health counselling is often limited to discussing birth control. The major difference between the Netherlands and GB is that GB TOP clinics more often offer free STI testing and prophylaxis to their clients., Conclusion: HCPs in Dutch TOP clinics consider STI testing an important part of their service, but financial barriers prevent testing on location. Dutch TOP clinics should offer STI tests to all women, and collaboration with public health services could improve STI testing and counselling for young people. Furthermore, clinics should treat all TOP clients with prophylactic azithromycin. This could prevent CT and other upper genital tract post-abortion infections.

Objectives: To develop prediction models for Chlamydia trachomatis (Ct) infection with different levels of detail in information, that is, from readily available data in registries and from additional questionnaires., Methods: All inhabitants of Rotterdam and Amsterdam aged 16-29 were invited yearly from 2008 until 2011 for home-based testing. Their registry data included gender, age, ethnicity and neighbourhood-level socioeconomic status (SES). Participants were asked to fill in a questionnaire on education, sexually transmitted infection history, symptoms, partner information and sexual behaviour. We developed prediction models for Ct infection using first-time participant data-including registry variables only and with additional questionnaire variables-by multilevel logistic regression analysis to account for clustering within neighbourhoods. We assessed the discriminative ability by the area under the receiver operating characteristic curve (AUC)., Results: Four per cent (3540/80 385) of the participants was infected. The strongest registry predictors for Ct infection were young age (especially for women) and Surinamese, Antillean or sub-Saharan African ethnicity. Neighbourhood-level SES was of minor importance. Strong questionnaire predictors were low to intermediate education level, ethnicity of the partner (non-Dutch) and having sex with casual partners. When using a prediction model including questionnaire risk factors (AUC 0.74, 95% CI 0.736 to 0.752) for selective screening, 48% of the participating population needed to be screened to find 80% (95% CI 78.4% to 81.0%) of Ct infections. The model with registry risk factors only (AUC 0.67, 95% CI 0.656 to 0.675) required 60% to be screened to find 78% (95% CI 76.6% to 79.4%) of Ct infections., Conclusions: A registry-based prediction model can facilitate selective Ct screening at population level, with further refinement at the individual level by including questionnaire risk factors., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: Prior research has shown that Dutch general practitioners (GPs) do not always offer HIV testing and the number of undiagnosed HIV patients remains high. We aimed to further investigate the frequency and reasons for (not) testing for HIV and the contribution of GPs to the diagnosis of HIV infections in the Netherlands., Design: Observational study., Setting: (1) Dutch primary care network of 42-45 sentinel practices where report forms during sexually transmitted infection (STI)-related consultations were routinely collected, 2008-2013. (2) Dutch observational cohort with medical data of HIV-positive patients in HIV care, 2008-2013., Outcome Measures: The proportion of STI-related consultations in patients from high-risk groups tested for HIV, with additional information requested from GPs on HIV testing preconsultation or postconsultation for whom HIV testing was indicated, but not performed. Next, information was collected on the profile of HIV-positive patients entering specialised HIV care following diagnosis by GPs., Results: Initially, an HIV test was reported (360/907) in 40% of STI-related consultations in high-risk groups. Additionally, in 26% of consultations an HIV test had been performed in previous or follow-up consultations or at different STI-care facilities. The main reasons for not testing were perceived insignificant risk; 'too' recent risk according to GPs or the reluctance of patients. The initiative of the patient was a strong determinant for HIV testing. GPs diagnosed about one third of all newly found cases of HIV. Compared with STI clinics, HIV-positive patients diagnosed in general practice were more likely to be older, female, heterosexual male or sub-Saharan African., Conclusions: In one-third of the STI-related consultations of persons from high-risk groups, no HIV test was performed in primary care, which is lower than previously reported. Risk-based testing has intrinsic limitations and implementation of new additional strategies in primary care is warranted., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: Early testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with late or advanced disease in HIV-infected patients in the Netherlands., Methods: HIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort. Risk factors for late presentation and advanced disease were analysed by multivariable logistic regression. Furthermore, geographical differences and time trends were examined., Results: Of 20,965 patients, 53% presented with late-stage HIV infection, and 35% had advanced disease. Late presentation decreased from 62% (1996) to 42% (2013), while advanced disease decreased from 46% to 26%. Late presentation only declined significantly among men having sex with men (MSM; p <0.001), but not among heterosexual males (p=0.08) and females (p=0.73). Factors associated with late presentation were: heterosexual male (adjusted OR (aOR), 1.59; 95% CI 1.44 to 1.75 vs MSM), injecting drug use (2.00; CI 1.69 to 2.38), age ≥ 50 years (1.46; CI 1.33 to 1.60 vs 30-49 years), region of origin (South-East Asia 2.14; 1.80 to 2.54, sub-Saharan Africa 2.11; 1.88 to 2.36, Surinam 1.59; 1.37 to 1.84, Caribbean 1.31; 1.13 to 1.53, Latin America 1.23; 1.04 to 1.46 vs the Netherlands), and location of HIV diagnosis (hospital 3.27; 2.94 to 3.63, general practitioner 1.66; 1.50 to 1.83, antenatal screening 1.76; 1.38 to 2.34 vs sexually transmitted infection clinic). No association was found for socioeconomic status or level of urbanisation. Compared with Amsterdam, 2 regions had higher adjusted odds and 2 regions had lower odds of late presentation. Results were highly similar for advanced disease., Conclusions: Although the overall rate of late presentation is declining in the Netherlands, targeted programmes to reduce late HIV diagnoses remain needed for all risk groups, but should be prioritised for heterosexual males, migrant populations, people aged ≥ 50 years and certain regions in the Netherlands., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Early detection and treatment of STI/HIV are public health priorities. Our objective was to compare characteristics of men who have sex with men (MSM) in Dutch data available in 2010 from EMIS, an international internet survey, Schorer Monitor, a Dutch internet survey, and data from STI- clinic visits, since these might be subject to different and unknown biases., Methods: Data from Dutch MSM Internet Surveys (EMISNL N = 3,787; Schorer Monitor, SMON N = 3,602), and 3,800 STI clinic visits (SOAP) were combined into one dataset. We included factors that were measured in all three databases. The socio-demographics included were age (at the time of the survey), zip code, and ethnicity. Behavioural variables included were the number of sexual partners, condom use with last sexual partner, drug use, being diagnosed with STI, being diagnosed with HIV, and HIV testing. Outcomes we investigated were being diagnosed with STI, HIV, and never been tested for HIV., Results: Logistic regressions showed that determinants for being diagnosed with STI were having more sexual partners, drug use, and having had an HIV test (aORs 1.3 to 17.1) in EMIS and SMON. Determinants for being diagnosed with HIV in all three databases were older age, living in Amsterdam, and having more partners (aORs 1.8 to 4.4). In EMIS and SMON, drug use, non-condom use, and having STI were additional determinants (aORs 1.6 to 8.9). Finally, determinants associated with never been tested for HIV were being younger (only SOAP), living outside of Amsterdam, having fewer partners, no drug use, and no STI (aORs 0.2 to 0.8)., Conclusions: Risk factors from internet surveys were largely similar, but differed from STI clinics, possibly because it involves self-reports rather than diagnoses or because of differences in timing. The difference between the internet surveys and STI clinic data is much less pronounced for having never been tested, suggesting both are appropriate for this outcome. These findings shed light on conclusions drawn from different data sources, as well as the comparability of recruitment strategies, the robustness of risk factors, consequences of phrasing questions differently, and on (policy) implications based on different data sources.

Objective: In three pilot regions of The Netherlands, all 16-29 year olds were invited to participate in three annual rounds of Chlamydia screening. The aim of the present study is to evaluate the cost-effectiveness of repeated Chlamydia screening, based on empirical data., Methods: A mathematical model was employed to estimate the influence of repeated screening on prevalence and incidence of Chlamydial infection. A model simulating the natural history of Chlamydia was combined with cost and utility data to estimate the number of major outcomes and quality-adjusted life-years (QALYs) associated with Chlamydia. Six screening scenarios (16-29 years annually; 16-24 years annually; women only; biennial screening; biennial screening women only; screening every five years) were compared with no screening in two sexual networks, representing both lower ('national network') and higher ('urban network') baseline prevalence. Incremental cost-effectiveness ratios (ICERs) for the different screening scenarios were estimated. Uncertainty and sensitivity analyses were performed., Results: In all scenarios and networks, cost per major outcome averted are above €5000. Cost per QALY are at least €50,000. The default scenario as piloted in the Netherlands was least cost-effective, with ICERs of €232,000 in the national and €145,000 in the urban sexual network. Results were robust in sensitivity analyses., Conclusions: It is unlikely that repeated rounds of Chlamydia screening will be cost-effective. Only at high levels of willingness to pay for a QALY (>€50,000) screening may be more cost-effective than no screening., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: To estimate HIV prevalence, the number of people living with HIV/AIDS (PLWHA) and the undiagnosed proportion in the Netherlands for 2012, and to compare these with published 2007 estimates., Design: Synthesis of all available data sources., Methods: Multi-Parameter Evidence Synthesis (MPES) was used to obtain estimates in mutually exclusive key populations at higher risk in three geographical regions (Amsterdam, Rotterdam, rest of the Netherlands). Data sources included HIV prevalence surveys, diagnoses at STI clinics, and registered cases in HIV care. Group specific estimates were reported as Bayesian posterior medians and 95% credible intervals (CrI)., Results: The 2012 model estimated 24,350 PLWHA (95% CrI 20,420-31,280) aged 15-70 years; 2,906 (+14%) more than in 2007. The estimated population HIV prevalence was 0.20% (95% CrI 0.17-0.26%). The overall proportion of undiagnosed HIV was lower in 2012 (34%, 95% CrI 22-49%) compared to 2007 (40%, 95% CrI 25-55%). After MSM, migrants from sub-Saharan Africa and the Caribbean formed the largest groups of PLWHA, but proportions of undiagnosed HIV remained high in these groups, 48% and 44% respectively. Amsterdam had lowest proportions undiagnosed for most key populations at higher risk, including MSM and migrants., Conclusions: In 2012, the number of PLWHA was higher compared to 2007, while the proportion of undiagnosed HIV was lower, especially among MSM. Higher HIV testing rates, earlier treatment, and an improved life expectancy may explain these differences. HIV interventions need to be expanded in all key populations at higher risk, with special focus on migrants and key populationsliving outside of Amsterdam.

Objective: To examine the effect of a laboratory-confirmed Chlamydia trachomatis (Ct) test result on subsequent sexual risk behavior in a large population-based screening program., Methods: The study population consisted of 16- to 29-year-old participants of the Chlamydia Screening Implementation who completed Ct testing and questionnaires in 2 or more rounds. The influence of a Ct test result on sexual behavior was analyzed by generalized estimating equation models, in which the Ct test result of the previous round was the independent variable and 1 of the 8 sexual risk behavior indicators was the dependent variable, adjusted for covariates., Results: Of 48,910 Chlamydia Screening Implementation participants with completed questionnaires and test results, 14.1% (n = 6802) and 2.6% (n = 1272) completed 2 and 3 rounds, respectively, and were included in this study. Analysis showed that Ct positives less often reported to "never" use condoms with a casual partner (%change pretest/posttest = -5.7% [-10.3 to -0.9]), whereas Ct negatives less often reported to "always" use condoms with a casual partner (-4.6% [-6.4 to -2.8]; odds ratio [95% confidence interval], 1.75 [1.09 to 2.80]). Ct positives also had more sexual partners in the subsequent round than did participants with a Ct-negative test result (relative risk [95% confidence interval], 1.14 [1.01 to 1.29])., Conclusions: Ct test results were associated with subsequent sexual risk behavior. In general, Ct positives were more likely to change their behavior after a Ct test result in a more positive and protective direction than Ct negatives, who were more likely to change their behavior toward more risky behavior. Effects over time after a Ct test should be investigated further, especially in the Ct negatives.

Background: Behaviour and related health outcomes of migrants have been suggested to shift towards the practices of the indigenous population of the host country. To investigate this, we studied generational differences in sexual behaviour between first- and second-generation migrants (FGMs and SGMs) in The Netherlands., Methods: In 2003-05, persons aged 16-70 years with origins in Surinam, the Antilles and Aruba were interviewed on their sexual behaviour in The Netherlands and their country of origin. The relationship of generation, age at migration and sexual behaviour was studied by multinomial logistic regression analyses., Results: Generational differences were observed regarding concurrent partnerships, anal sex and history of sexually transmitted infection. Compared with FGMs who migrated at an age >25 years, those who migrated between 10 and 25 years of age were more likely to report concurrency [odds ratio (OR): 1.52, 95% confidence interval (CI): 1.14-2.04], whereas SGMs were less likely to report concurrency (OR: 0.65, 95% CI: 0.43-0.98). FGMs who migrated before the age of 10 were more likely to have had anal sex (OR: 1.90, 95% CI: 1.34-2.71) or a sexually transmitted infection diagnosis (OR: 1.80, 95% CI: 1.20-2.71) than those who had migrated at >25 years of age., Conclusion: Our study shows that not only SGMs but also FGMs who migrated at an early age tend to differ from the sexual patterns of FGMs who migrated at an older age. Generational differences in sexual behaviour could be explained by acculturation and increased identity with the values of the host country.

Objective: To enhance partner notification (PN) practices in Dutch STI clinics, a PN training using motivational interviewing as core strategy was offered to STI professionals and evaluated., Methods: The effectiveness of PN training on professionals' attitude, self-efficacy, skills and behavior toward PN, was examined using within-subject and between-subject comparison. Before the training and at three months follow-up, a questionnaire was completed by the intervention group (n=54) and a non-random control group (n=37)., Results: In the within-subject comparison, positive changes were observed in self-efficacy, skills, and PN behaviors (all p<.05), but not in attitudes toward PN. When we examined differences in change-scores between the intervention and control group, self-efficacy was no longer significant., Conclusion: The PN training significantly improved PN skills and -behavior, but had no effect on professionals' attitudes or self-efficacy toward PN. The selection of a convenience control sample seems to offer a more rigorous test of hypotheses than pre-post evaluation only., Practice Implications: The beneficial effect of PN training of STI professionals seems to support a wider roll-out of the training to all STI clinics in the Netherlands, although effects on the number of partners notified and transmissions prevented need to be examined in future research., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

A population-based anti-hepatitis C virus (HCV) prevalence is important for surveillance purposes and it provides insight into the burden of disease. The outcomes of recent studies in the general Dutch population as well as recent HCV data from specific risk groups including migrants, men who have sex with men (MSM) and injecting drug users (IDUs), were implemented in a modified version of the Workbook Method (a spreadsheet originally designed for HIV estimations), to estimate Dutch HCV seroprevalence. The estimated national seroprevalence of HCV was 0·22% (min 0·07%, max 0·37%), corresponding to 28 100 (min n = 9600, max n = 48 000) HCV-infected individuals in The Netherlands. Of these, first-generation migrants from HCV-endemic countries (HCV prevalence ≥2%) accounted for the largest HCV-infected group, followed by IDUs and HIV-positive MSM.

Introduction: In a systematic internet-based Chlamydia Screening Implementation Programme in The Netherlands, all chlamydia-positive participants automatically received a testkit after 6 months to facilitate early detection of repeat infections. The authors describe participation in repeat testing and prevalence and determinants of repeat infection during three consecutive annual screening rounds., Methods: Data collection included information on testkits sent, samples received and results of laboratory tests at time of baseline test and retest; (sexual) behavioural variables and socio-demographic variables were assessed. Chlamydia positives were requested to answer additional questions about treatment and partner notification 10 days after checking their results., Results: Retest rate was 66.3% (2777/4191). Retest chlamydia positivity was 8.8% (242/2756) compared with a chlamydia positivity at first screening test of 4.1%. Chlamydia positivity was significantly higher in younger age groups (14.6% in 16-19 years, 8.5% and 5.5% in 20-24 and 25-29 years; p<0.01); in participants with lower education (15.2% low, 11.1% medium and 5.1% high; p<0.001) and in Surinamese/Antillean (13.1%), Turkish/Moroccan (12.9%) and Sub-Saharan African participants (18.6%; p<0.01). At baseline, 88.7% infected participants had reportedly been treated and treatment of current partner was 80.1%., Discussion: Automated retesting by sending a testkit after 6 months to all chlamydia positives achieved high retest uptake and yielded a positivity rate twice as at baseline and can therefore be recommended as an additional strategy for chlamydia control. The high rate of repeat infections among known risk groups suggests room for improvement in patient case management and in effective risk reduction counselling.

The Netherlands has approximately 20,000 registered HIV-infected patients. The current HIV prevention policy consisting of condom use and active HIV testing does not effectively mitigate the HIV epidemic in all risk groups. In July of 2012, tenofovir/emtricitabine (TDF/FTC) was approved by the American Food and Drug Administration (FDA) for pre-exposure prophylaxis (PrEP) for long-term use in persons who exhibit frequent risky and unsafe sexual behaviour. With once-daily use and good therapy compliance, TDF/FTC has proved to be effective as PrEP, and few side effects are reported. Drawbacks in the use of TDF/FTC as PrEP are the potential risk of viral resistance and reduced condom use, the relatively high cost and the intensive counselling required. In special cases, long-term PrEP could enhance the current Dutch preventive policy. Further research is needed into the practical feasibility and protective efficacy of the ad hoc use of TDF/FTC as PrEP before a high-risk contact occurs.

Background: A large trial to investigate the effectiveness of population based screening for chlamydia infections was conducted in the Netherlands in 2008-2012. The trial was register based and consisted of four rounds of screening of women and men in the age groups 16-29 years in three regions in the Netherlands. Data were collected on participation rates and positivity rates per round. A modeling study was conducted to project screening effects for various screening strategies into the future., Methods and Findings: We used a stochastic network simulation model incorporating partnership formation and dissolution, aging and a sexual life course perspective. Trends in baseline rates of chlamydia testing and treatment were used to describe the epidemiological situation before the start of the screening program. Data on participation rates was used to describe screening uptake in rural and urban areas. Simulations were used to project the effectiveness of screening on chlamydia prevalence for a time period of 10 years. In addition, we tested alternative screening strategies, such as including only women, targeting different age groups, and biennial screening. Screening reduced prevalence by about 1% in the first two screening rounds and leveled off after that. Extrapolating observed participation rates into the future indicated very low participation in the long run. Alternative strategies only marginally changed the effectiveness of screening. Higher participation rates as originally foreseen in the program would have succeeded in reducing chlamydia prevalence to very low levels in the long run., Conclusions: Decreasing participation rates over time profoundly impact the effectiveness of population based screening for chlamydia infections. Using data from several consecutive rounds of screening in a simulation model enabled us to assess the future effectiveness of screening on prevalence. If participation rates cannot be kept at a sufficient level, the effectiveness of screening on prevalence will remain limited.

A population-based anti-hepatitis C virus (HCV) prevalence is important for surveillance purposes and it provides an insight into the burden of disease. In The Netherlands, a recent HCV seroprevalence estimate is not available. This national population-based cross-sectional serosurvey (PIENTER-2) resulted in a weighted national HCV seroprevalence of 0.30% (95% confidence interval 0.05-0.55%). About 70% of the HCV positive individuals found were born in an HCV-endemic country.

Objective: To evaluate the effectiveness of register based, yearly chlamydia screening., Design: Controlled trial with randomised stepped wedge implementation in three blocks., Setting: Three regions of the Netherlands: Amsterdam, Rotterdam, and South Limburg., Participants: 317 304 women and men aged 16-29 years listed on municipal registers at start of trial., Intervention: From March 2008 to February 2011, the Chlamydia Screening Implementation programme offered yearly chlamydia screening tests. Postal invitations asked people to use an internet site to request a kit for self collection of samples, which would then be sent to regional laboratories for testing. Treatment and partner notification were done by the general practitioner or at a sexually transmitted infection clinic., Main Outcome Measures: Primary outcomes were the percentage of chlamydia tests positive (positivity), percentage of invitees returning a specimen (uptake), and estimated chlamydia prevalence. Secondary outcomes were positivity according to sex, age, region, and sociodemographic factors; adherence to screening invitations; and incidence of self reported pelvic inflammatory disease., Results: The participation rate was 16.1% (43 358/269 273) after the first invitation, 10.8% after the second, and 9.5% after the third, compared with 13.0% (6223/48 031) in the control block invited at the end of round two of the intervention. Chlamydia positivity in the intervention blocks at the first invitation was the same as in the control block (4.3%) and 0.2% lower at the third invitation (odds ratio 0.96 (95% confidence interval 0.83 to 1.10)). No substantial decreases in positivity were seen after three screening rounds in any region or sociodemographic group. Among the people who participated three times (2.8% of all invitees), positivity fell from 5.9% to 2.9% (odds ratio 0.49 (0.47 to 0.50))., Conclusions: There was no statistical evidence of an impact on chlamydia positivity rates or estimated population prevalence from the Chlamydia Screening Implementation programme after three years at the participation levels obtained. The current evidence does not support a national roll out of this register based chlamydia screening programme., Trial Registration: NTR 3071 (Netherlands Trial Register, www.trialregister.nl).

Ethnic disparities in chlamydia infections in The Netherlands were assessed, in order to compare two definitions of ethnicity: ethnicity based on country of birth and self-defined ethnicity. Chlamydia positivity in persons aged 16-29 years was investigated using data from the first round of the Chlamydia Screening Implementation (CSI, 2008-2009) and surveillance data from STI centres (2009). Logistic regression modelling showed that being an immigrant was associated with chlamydia positivity in both CSI [adjusted odds ratio (aOR) 2·3, 95% confidence interval (CI) 2·0-2·6] and STI centres (aOR 1·4, 95% CI 1·3-1·5). In both settings, 60% of immigrants defined themselves as Dutch. Despite the difference, classification by self-defined ethnicity resulted in similar associations between (non-Dutch) ethnicity and chlamydia positivity. However, ethnicity based on country of birth explained variation in chlamydia positivity better, and is objective and constant over time and therefore more useful for identifying young persons at higher risk for chlamydia infection.

Background & Aims: Little is known about the HCV prevalence in non-Western migrant populations. To determine whether targeted HCV screening and prevention programs for migrants are needed, we examined HCV prevalence and determinants among non-Western, Western migrants, and the native Dutch population in the Netherlands., Methods: Data were obtained from four surveys: (1) 3895 heterosexual visitors recruited during biannual surveys at the STI-clinic Amsterdam, 2007-2009; (2) random sample of 4563 pregnant women in Amsterdam, 2003; (3) population-based random sample of 1309 inhabitants of Amsterdam, 2004; (4) population-based random sample of 4428 people living in the Netherlands, 2006-2007. Characteristics associated with HCV-positivity were examined and phylogenetic analysis was used to obtain insight in the geographical origin of HCV strains., Results: HCV seroprevalence in the four surveys was low (0.3-0.6%). In total 4860/14,195 (34%) were non-Western and 9329/14,195 (66%) Western participants (including Dutch). First-generation non-Western migrants were more likely to be HCV-positive (0.7-2.3%) than Western participants (0.1-0.4%). Except for survey 3, second-generation non-Western migrants had a lower HCV prevalence than first-generation migrants, comparable to Western migrants and the Dutch population. Phylogenetic analysis showed that the majority of the HCV-positive, first-generation non-Western non-European migrants were infected with endemic strains which are rarely observed in Europe., Conclusions: First-generation non-Western migrants are at increased risk for HCV. Phylogenetic analysis suggests that transmission likely took place in the country of origin, causing introduction but no further transmission of endemic HCV strains in the Netherlands. HCV screening and prevention programs should target first-generation, but not second-generation, non-Western migrants., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: 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., Methods: The results of antenatal screening (2006-2008) were compared with data from pregnant women and newborns from other data sources., Results: 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., Conclusions: 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)].

We aimed to study patterns of HIV transmission among Suriname, The Netherlands Antilles, and The Netherlands. Fragments of env, gag, and pol genes of 55 HIV-infected Surinamese, Antillean, and Dutch heterosexuals living in The Netherlands and 72 HIV-infected heterosexuals living in Suriname and the Antilles were amplified and sequenced. We included 145 pol sequences of HIV-infected Surinamese, Antillean, and Dutch heterosexuals living in The Netherlands from an observational cohort. All sequences were phylogenetically analyzed by neighbor-joining. Additionally, HIV-1 mobility among ethnic groups was estimated. A phylogenetic tree of all pol sequences showed two Surinamese and three Antillean clusters of related strains, but no clustering between ethnic groups. Clusters included sequences of individuals living in Suriname and the Antilles as well as those who have migrated to The Netherlands. Similar clustering patterns were observed in env and gag. Analysis of HIV mobility among ethnic groups showed significantly lower migration between groups than expected under the hypothesis of panmixis, apart from higher HIV migration between Antilleans in The Netherlands and all other groups. Our study shows that HIV transmission mainly occurs within the ethnic group. This suggests that cultural factors could have a larger impact on HIV mobility than geographic distance.

Objective: Evaluation of the effectiveness of antenatal screening in the Netherlands for HIV, hepatitis B virus (HBV) and syphilis, in preventing mother-to-child transmission., Design: Descriptive., Methods: The results of antenatal screening in the period 2006-2008 were compared with data from pregnant women and newborns from other data sources., Results: 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. 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., Conclusion: 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.

To gain insight into the transmission of HIV and sexually transmitted infection (STI) among large migrant groups in The Netherlands, we studied the associations between their demographic and sexual characteristics, in particular condom use, and their sexual mixing patterns with other ethnic groups. In 2002-2005, cross-sectional surveys were conducted among migrants from Surinam (Afro- and Hindo-), the Netherlands Antilles, Cape Verde, and Ghana at social venues in three large cities. A questionnaire was administrated and a saliva sample was collected for HIV antibody testing. Of 2105 migrants recruited, 1680 reported sexual contacts, of whom 41% mixed sexually with other ethnicities, including the indigenous Dutch population. Such disassortative mixing was associated with being second-generation migrant, having several sexual partners, and having a steady and concurrent casual partner. Less disassortative mixing occurred in participants reporting visiting the country of origin. The association between condom use and sexual mixing differed by gender, with men using condoms inconsistently being most likely to be mixing with the Dutch indigenous population. HIV infection and recent STI treatment were not associated with disassortative mixing. This study shows substantial sexual mixing among migrant groups. Since disassortative mixing is more prevalent in second-generation migrants, it might increase in the upcoming years. The mixing patterns in relation to concurrency and the reported condom use in this study suggest a possibly increased level of HIV/STI transmission not only within migrant groups but also between migrant groups, especially via men who mix with the indigenous population and via migrant women who mix with non-Dutch casual partners. Although the observed HIV prevalence in migrants (0.6%) is probably too low to lead to much HIV transmission between ethnicity groups, targeted prevention measures are needed to prevent transmission of other STI.

Background: The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced., Results: In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration. For Poland no significant migratory pathways were inferred., Conclusion: Subtype B phylogeographies provide a new insight about the geographical distribution of viral lineages, as well as the significant pathways of virus dispersal across Europe, suggesting that intervention strategies should also address tourists, travellers and migrants.

Objective: To gain insight into hepatitis B virus (HBV) transmission in the Netherlands., Design: Descriptive., Method: During 2004, epidemiological data and blood samples (if available) were collected for all reported cases of acute HBV infections in the Netherlands. Following DNA isolation and amplification a 648 base pairs fragment of the HBV S gene was sequenced and subjected to phylogenetic analysis. The sequencing details were also linked to epidemiological information., Results: In 2004, 291 cases ofacute HBV infections were reported. Blood samples were received from 171 patients (59%), and the genotype could be determined for 158 patients (54%). 6 genotypes were identified: A (64%), B (3%), C (3%), D (21%), E (5%) and F (4%). Of all patients with genotype A, 52% had been infected via homosexual or bisexual contact and 16% via heterosexual contact. Of all patients with genotype D, 42% had been infected via heterosexual contact and 15% via homosexual or bisexual contact. The genotype A cluster was extremely homogeneous with many identical sequences, while genotype B-E clusters were more heterogeneous. 4 identical sequences were found within genotype F, but the patients could not be epidemiologically linked., Conclusion: Sexual transmission, particularly via homosexual or bisexual contact in men, formed the most important risk factor for acquiring an acute HBV infection. Genotype A was predominant in the Netherlands, especially among homosexual or bisexual men. Most infections within genotype D occurred as a result of heterosexual contact. The results show that there was ongoing transmission of HBV in homosexual or bisexual men, while in heterosexuals more cases of new introduction were seen, possibly via chronic carriers from areas where HBV is endemic.

An effective vaccine is available for the hepatitis B virus (HBV), which is a very contagious human pathogen. The prevalence of chronic HBV infection is very low in the Netherlands (<0.5%), and no universal vaccination is in place. Instead, a program of vaccination for targeted groups at high risk of HBV exposure has been implemented. Because transmission of HBV can occur by various routes, the effectiveness of this targeted vaccination strategy is difficult to assess. Molecular typing data for the surface protein encoding gene of HBV isolates, in combination with epidemiological data, provide some insight into the main transmission routes. Due to the low mutation rate of the HBV genome, many isolates have identical S region sequences, which hampers phylogenetic analysis and identification of transmission chains. The molecular epidemiological analysis of acute HBV isolates based on the surface and core protein encoding regions were compared. The nucleotide diversity found in the C region was statistically significant greater (1.5 times) than in the S region, and phylogenetic analysis based on the C region showed a higher resolution. C region analysis resulted in an almost 50% reduction of genotype A isolates with identical sequences. C region analysis also indicated that no long-chain transmission of genotype D strains is occurring in the Netherlands, as all genotype D isolates have unique C region sequences. Defining the goals of molecular typing of HBV isolates should precede the choice for phylogenetic analysis on the basis of either C or S region sequences., ((Copyright) 2007 Wiley-Liss, Inc.)

Objective: To study the trends in the prevalence of hepatitis B infections in the Netherlands on the basis of reported cases., Design: Retrospective, descriptive., Method: Analysis of data collected from the obligatory notification of hepatitis B to the Dutch Public Health Services in the Netherlands in the period 2002-2005., Results: In the period from January 2002 to December 2005, 7352 hepatitis B virus (HBV) infections were reported, of which 1168 (16%) were acute and 5849 (80%) were chronic infections. Of the acute HBV infections, 34% were transmitted by homo- or bisexual contact and 25% by heterosexual contact. The number of reports of acute HBV infection due to heterosexual transmission increased significantly and originated relatively more often in Dutch patients. The number of reports of chronic HBV infection in men increased significantly; in women there was a decrease over time. Of the chronic HBV infections, 40% were transmitted from mother to child; this was reported especially often by patients from HBV endemic areas., Conclusion: Sexual contact was the most important risk factor for the transmission of acute HBV infections, whereas vertical transmission was the greatest risk factor by far for chronic HBV infection. Transmission via heterosexual contact had become increasingly important in the transmission of acute HBV; transmission by homo- or bisexual contact remained constant. Immigration continued to play an important role in the epidemiology of HBV in the Netherlands; the majority of the chronic carriers had been born and infected in an HBV endemic area.

To gain insight into hepatitis B virus (HBV) transmission in the Netherlands, epidemiological data and sera were collected from reported cases of acute HBV infections in the Netherlands in 2004. Cases were classified according to mode of transmission. A fragment of the S-gene of HBV (648 bp) was amplified, sequenced, and subjected to phylogenetic analysis. Of the 291 acute HBV cases reported in 2004, 158 (54%) were available for genotyping. Phylogenetic analysis identified 6 genotypes: A (64%), B (3%), C (3%), D (21%), E (5%) and F (5%). Of HBV infected men having sex with men, 86% were infected with genotype A, accounting for 43% of all patients infected with this genotype. There were only three reported cases of injecting drug use of which one was available for sequencing (genotype A). Unlike the genotype A cluster, sequences within the genotype B-E clusters were heterogenic. Within genotype F, several isolates had identical sequences, but patients could not be epidemiologically linked. Sexual transmission, particularly by men having sex with men was the most important transmission route for HBV. Injecting drug use plays a minor role. Genotype A is predominant in the Netherlands, especially among men having sex with men. In addition to imported strains, there seems to be a pool of related but non-identical strains circulating among chronic carriers in the migrant population, from which occasionally new patients are infected, primarily by heterosexual transmission.

Background: The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug resistance substitutions. This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (>600 of non-B subtype) isolated from anti-retroviral-naive patients in Europe., Methods: The genetic barrier was calculated as the sum of transitions (scored as 1) and/or transversions (2.5) required for evolution to any major drug resistance substitution. In addition, the number of minor protease substitutions was determined for every subtype., Results: Few dissimilarities were found. An increased genetic barrier was calculated for I82A (subtypes C and G), V108I (subtype G), V118I (subtype G), Q151M (subtypes D and F), L210W (subtypes C, F, G, and CRF02&#95;AG), and P225H (subtype A) (P < 0.001 compared with subtype B). A decreased genetic barrier was found for I82T (subtypes C and G) and V106M (subtype C) (P < 0.001 vs subtype B). Conversely, minor protease substitutions differed extensively between subtypes., Conclusions: Based on the calculated genetic barrier, the rate of drug resistance development may be similar for different HIV-1 subtypes. Because of differences in minor protease substitutions, protease inhibitor resistance could be enhanced in particular subtypes once the relevant major substitutions are selected.

Background: Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) can impair the response to combination therapy. Widespread transmission of drug-resistant variants has the disturbing potential of limiting future therapy options and affecting the efficacy of postexposure prophylaxis., Methods: We determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996-2002., Results: In Europe, 1 of 10 antiretroviral-naive patients carried viruses with > or = 1 drug-resistance mutation. Recently infected patients harbored resistant variants more often than did chronically infected patients (13.5% vs. 8.7%; P=.006). Non-B viruses (30%) less frequently carried resistance mutations than did subtype B viruses (4.8% vs. 12.9%; P<.01). Baseline resistance increased over time in newly diagnosed cases of non-B infection: from 2.0% (1/49) in 1996-1998 to 8.2% (16/194) in 2000-2001., Conclusions: Drug-resistant variants are frequently present in both recently and chronically infected therapy-naive patients. Drug-resistant variants are most commonly seen in patients infected with subtype B virus, probably because of longer exposure of these viruses to drugs. However, an increase in baseline resistance in non-B viruses is observed. These data argue for testing all drug-naive patients and are of relevance when guidelines for management of postexposure prophylaxis and first-line therapy are updated.

Objective: To gain insight into the prevalence of HIV infection, the determinants thereof and the risk behaviour in injecting drug users (IDUs) in Rotterdam, The Netherlands, in 2002 in comparison to the HIV survey data from 1994 and 1997., Design: Questionnaire study., Method: In 1994-2002, three periodic HIV surveys were conducted in Rotterdam among IDUs using semi-structured questionnaires on risk behaviour and saliva samples for HIV-antibody determination. In the present study, the data for 2002 were analysed and compared with those from 1994 and 1997., Results: The number of participants recruited was 494, 470 and 452, respectively. HIV prevalence did not change over time: 1994: 11.4%, 1997: 9.4% and 2002: 10.2%. In the 2002 survey, independent risk factors for HIV were homelessness and onset of injecting drug use at an early age. The percentage of IDUs that had recently shared needles declined from 18% in 1994 to 8% in 2002. Risky sexual behaviour remained prevalent: inconsistent condom use was reported by 85% with steady partners, 43% with casual partners and 31% with clients. The IDUs who knew that they were HIV positive used condoms consistently more often., Conclusion: The combination of a relatively high HIV prevalence among IDUs in Rotterdam and the high level of unsafe sexual behaviour results in a serious risk of further spread of HIV among both IDUs and the general population.

Objective: To describe the results of HIV-surveillance activities in the Netherlands between 1987 and 2001., Design: Descriptive., Method: Data were obtained from HIV-surveillance at STI-clinics, laboratory-surveillance in the region Arnhem, surveillance among injecting drug users, the AIDS-notification, STI-registration and the Amsterdam cohort studies on HIV/AIDS., Results: In the Netherlands, the highest HIV-prevalences were found among injecting drug users (1-26%) and homo- and bisexual men (0-17%). In these high-risk populations, an increase in HIV-prevalence and--incidence, respectively, was found among injecting drug users in Heerlen and homosexual men (> 35 years of age) in Amsterdam. The HIV-prevalence was lower among heterosexuals in the Netherlands (0-2%). However, in certain local populations an increase was seen. In both Amsterdam and Rotterdam, the HIV-prevalence was higher in individuals tested anonymously than in those tested by name., Conclusion: Local increases in HIV-infections have been observed recently, in both high- and medium-risk populations.

To gain insight into the spread of hepatitis B among various risk groups in Amsterdam a 6-year (1992-1997) retrospective DNA sequencing study was carried out on isolates from stored sera from reported primary cases of acute hepatitis B infection. Cases were classified according to risk behavior, as determined in interviews. Of the available serum, a selected region of hepatitis B-virus-DNA was amplified and sequenced. The nucleotide alignments were subjected to phylogenetic tree analysis. When nucleotide alignments were subjected to phylogenetic analysis, the strains of 54 isolates, 26% of the 204 reported primary cases, clustered in five genotypes: A, C, D, E, and F. In genotype A, a cluster related to men having sex with men was identified. In genotype D, two subclusters could be identified: one was related to injecting drug use and another was related to the Moroccan population in Amsterdam. The remaining strains showed a high genetic variability within three different genotypes: F, E, and C. Of the 14 identical isolates in the "homosexual men cluster," one was isolated from a female heterosexual. Of the 14 identical strains in the "drug users strain," six were from non-drug using heterosexual active individuals. In the cluster of twelve isolates related to hepatitis B-endemic areas, probable modes of transmission were varied. Sequence analysis provides important insight into the spread of hepatitis B among various high-risk groups. The analysis indicates that the prevention strategy in The Netherlands fails to stop transmission of hepatitis B from persistently infected individuals originating from hepatitis B endemic countries., (Copyright 2002 Wiley-Liss, Inc.)

Objective: To examine the epidemiological factors influencing the distribution and spread of HIV-1 subtypes among heterosexuals in the Netherlands., Method: A nationwide serosurveillance in 21 HIV/AIDS centres from 1997 to 1999 involved 200 individuals for whom the mode of HIV transmission was heterosexual contact or unknown. HIV-1 subtypes were determined by phylogenetic analysis of env V3 sequences and correlated with sociodemographic characteristics of the subjects and their sexual partners., Results: HIV-1 subtype B infection occurred in 121 subjects (60%). Non-B subtypes were identified in 31 (A), 24 (C), 10 (D), six (E), four (F) and three (G) individuals; one had an unclassified subtype. The proportion of subtype B was about 60% in four of the six regions of the Netherlands, but in the Northwest and Southwest regions these proportions were 76% and 46%, respectively. The Surinamese and Antilleans, large immigrant groups, were all infected with subtype B, as were almost all individuals with an unknown source. The proportions of non-B viruses did not change significantly over time in Amsterdam, where subtyping was available from 1988 onward, but a shift in the various subtype B strains was observed, suggesting introductions of new subtype B strains in Amsterdam., Conclusion: To date, HIV-1 non-B subtypes in the Netherlands are still found predominantly among heterosexuals with an epidemiological link with sub-Saharan Africa. Despite continuing introductions of non-B subtypes, the B/non-B distribution has been stable over time, most likely as a result of introductions of subtype B strains from Caribbean and South American countries.

Objective: To reconstruct the epidemiological relationships of the HIV epidemics among injecting drug users (IDU) in western Europe., Methods: HIV env V3 sequences of and epidemiological data were obtained from 145 IDU who seroconverted in three sequential periods: 1984-1988, 1989-1992 and 1993-1997. The sequences were phylogenetically analysed and examined for signature patterns characteristic of northern European IDU, including the conserved GGC codon in the V3 loop., Results: Subpopulations of genetically related HIV strains were observed in Italy, France, Scotland and Spain, in contrast to the Netherlands, Austria and Switzerland. This difference between the two groups of countries suggests that the HIV epidemics amongst IDU in the latter group was caused by multiple virus introductions. In Edinburgh and the surrounding area, most IDU were infected with the same GGC strain over the 12-year study period. The epidemic among IDU in north-western Europe started with GGC viruses, whereas in south-western Europe non-GGC viruses predominated. This geographical separation has faded during the course of the epidemic, most likely because of virus exchange among IDU populations.

Objective: To study the molecular epidemiology of HIV-1 subtype B amongst heterosexually infected individuals in The Netherlands., Design: The study population comprised 54 individuals infected by subtype B viruses through heterosexual contacts. Serum samples were collected between 1988 and 1996., Methods: Sequences of the gp120 V3 region were obtained from serum samples and analysed by using the signature pattern and phylogenetic methods., Results: In 22 (41%) out of 54 subtype B sequences from heterosexually infected individuals, the synonymous nucleotide substitution in the second glycine codon at the tip of the V3 loop (the GGC pattern), previously identified as specific for Dutch injecting drug users (IDU), was found. The other previously described IDU sequence patterns were observed significantly more often among GGC- than among non-GGC-containing sequences. In addition, we identified another amino-acid change specific for the GGC sequences. In the phylogenetic and principal coordinate analyses, the GGC sequences from heterosexually infected individuals clustered separately from the non-GGC sequences and together with the IDU consensus sequence. Both the nonsynonymous and particularly the synonymous distances amongst the GGC sequences were significantly lower than amongst the non-GGC sequences., Conclusions: Our data provide evidence for a common origin of the viruses in Dutch IDU and the GGC viruses in heterosexuals. We suggest that a considerable proportion of the viruses in heterosexually infected individuals in The Netherlands may have originated from Dutch IDU.