Amy Matser

Decline in incidence of HIV and hepatitis C virus infection among injecting drug users in Amsterdam; evidence for harm reduction?

AIMS In Amsterdam, HIV prevalence has nearly halved among injecting drug users (IDU) since 1990. Hepatitis C virus (HCV) prevalence also declined; HIV and HCV incidence dropped to nearly zero. We examined possible explanations for these time trends, among which the implementation of harm reduction measures aimed at reducing the risk behaviour of IDU. DESIGN We used individual-based modelling of the spread of HIV and HCV. Information about demographic parameters was obtained from the Amsterdam Cohort Study (ACS) among drug users. The model included changes in inflow of new IDU and death rates over time, the latter dependent on age and time since HIV seroconversion. We considered different scenarios of risk behaviour. SETTING IDU in Amsterdam. MEASUREMENTS Simulated HIV and HCV incidence and prevalence were compared with ACS data. FINDINGS Assuming that harm reduction measures had led to a strong decrease in risk behaviour over time improved the model fit (squared residuals decreased by 30%). However, substantial incidence and HIV prevalence decline were already reproduced by incorporating demographic changes into the model. In particular, lowered disease spread might be a result of depletion of high-risk IDU among those at risk for disease, and a decrease in the number of high-risk individuals in the population due to HIV-related mortality. CONCLUSIONS Marked decreases in HIV and HCV in Amsterdam since 1990 could be due partly to harm reduction measures; however, they may also be attributable largely to changes in the IDU population. Future research aimed at quantifying the benefits of interventions should not neglect the impact of natural epidemic progression and demographic changes.

Distinct Transmission Networks of Chlamydia trachomatis in Men Who Have Sex with Men and Heterosexual Adults in Amsterdam, The Netherlands

Background Genovar distributions of Chlamydia trachomatis based on ompA typing differ between men who have sex with men (MSM) and heterosexuals. We investigated clonal relationships using a high resolution typing method to characterize C. trachomatis types in these two risk groups. Methods C. trachomatis positive samples were collected at the STI outpatient clinic in Amsterdam between 2008 and 2010 and genotyped by multilocus sequence typing. Clusters were assigned using minimum spanning trees and these were combined with epidemiological data of the hosts. Results We typed 526 C. trachomatis positive samples: 270 from MSM and 256 from heterosexuals. Eight clusters, containing 10–128 samples were identified of which 4 consisted of samples from MSM (90%–100%), with genovars D, G, J, and L2b. The other 4 clusters consisted mainly of samples from heterosexuals (87%–100%) with genovars D, E, F, I, and J. Genetic diversity was much lower in the MSM clusters than in heterosexual clusters. Significant differences in number of sexual partners and HIV-serostatus were observed for MSM–associated clusters. Conclusions C. trachomatis transmission patterns among MSM and heterosexuals were largely distinct. We hypothesize that these differences are due to sexual host behavior, but bacterial factors may play a role as well.

Elasticity analysis in epidemiology: an application to tick-borne infections.

The application of projection matrices in population biology to plant and animal populations has a parallel in infectious disease ecology when next-generation matrices (NGMs) are used to characterize growth in numbers of infected hosts (R(0)). The NGM is appropriate for multi-host pathogens, where each matrix element represents the number of cases of one type of host arising from a single infected individual of another type. For projection matrices, calculations of the sensitivity and elasticity of the population growth rate to changes in the matrix elements has generated insight into plant and animal populations. These same perturbation analyses can be used for infectious disease systems. To illustrate this in detail we parameterized an NGM for seven tick-borne zoonoses and compared them in terms of the contributions to R(0) from three different routes of transmission between ticks, and between ticks and vertebrate hosts. The definition of host type may be the species of the host or the route of infection, or, as was the case for the set of tick-borne pathogens, a combination of species and the life stage at infection. This freedom means that there is a broad range of disease systems and questions for which the methodology is appropriate.

The effect of hepatitis C treatment and human immunodeficiency virus (HIV) co-infection on the disease burden of hepatitis C among injecting drug users in Amsterdam.

AIMS The hepatitis C virus (HCV) disease burden among injecting drug users (IDUs) is determined by HCV incidence, the long latency period of HCV, competing mortality causes, presence of co-infection and HCV treatment uptake. We examined the effect of these factors and estimated the HCV disease burden in Amsterdam. DESIGN A Markov model was developed, incorporating HCV and human immunodeficiency virus (HIV), and parameterized with data from the Amsterdam Cohort Studies, surveillance studies and literature. SETTING IDU population of Amsterdam. MEASUREMENTS HCV infection simulated from its acute phase to HCV-related liver disease (i.e. decompensated cirrhosis and hepatocellular carcinoma). FINDINGS The HCV prevalence among IDUs in Amsterdam increased to approximately 80% in the 1980s. From 2011 to 2025, the HCV-related disease prevalence will accordingly rise by 36%, from 57 cases (95% range 33-94) to 78 (95% range 43-138), respectively. In total, 945 (95% range 617-1309) individuals will develop HCV-related liver disease. This burden would have been 33% higher in the absence of HIV, resulting in 1219 cases (95% range 796-1663). In Amsterdam, 25% of HIV-negative IDUs receive successful HCV treatment, reducing the cumulative disease burden by 14% to 810 (95% range 520-1120). Further reduction of 36% can be achieved by improving treatment, resulting in 603 cases (95% range 384-851). CONCLUSIONS The hepatitis C virus burden among injecting drug users in Amsterdam has been reduced by a high competing mortality rate, particularly caused by HIV infection, and to a smaller extent by hepatitis C virus treatment. Improved hepatitis C virus treatment is expected to contribute to reduce the future hepatitis C virus disease burden.

Distinct Neisseria gonorrhoeae Transmission Networks Among Men Who Have Sex With Men in Amsterdam, the Netherlands

BACKGROUND Molecular typing was used to elucidate Neisseria gonorrhoeae transmission networks among men who have sex with men (MSM) in Amsterdam, the Netherlands. We determined whether clusters of patients infected with specific N. gonorrhoeae genotypes were related to various epidemiological characteristics. METHODS MSM (age ≥18 years) visiting the sexually transmitted infections (STI) clinic between July 2008 and August 2009 were eligible. After STI screening, participants completed a behavioral questionnaire concerning the previous 6 months. N. gonorrhoeae cultures were genotyped using multiple-locus variable-number tandem repeat analysis typing. RESULTS We obtained 278 N. gonorrhoeae-positive isolates from 240 MSM. Five large clusters (≥10 isolates), a unique sixth cluster (n = 9), and 8 smaller clusters (5-9 isolates) were identified. Prevalence of human immunodeficiency virus differed between clusters I and VI (P = .003), ranging from 27.8% to 100%. Receptive unprotected anal intercourse was frequently reported by MSM (51.8%) but did not differ significantly among clusters. Significant differences were identified concerning the participants history of syphilis (P = .030), having met partners at a popular sex venue in Amsterdam (P = .048), and meeting partners outside Amsterdam (P = .036). CONCLUSIONS Distinct N. gonorrhoeae transmission networks were present in a mixed high-risk MSM population; concordance between clusters and epidemiological characteristics was present but not marked.

Is adding HCV screening to the antenatal national screening program in Amsterdam, the Netherlands, cost-effective?

Introduction Hepatitis C virus (HCV) infection can lead to severe liver disease. Pregnant women are already routinely screened for several infectious diseases, but not yet for HCV infection. Here we examine whether adding HCV screening to routine screening is cost-effective. Methods To estimate the cost-effectiveness of implementing HCV screening of all pregnant women and HCV screening of first-generation non-Western pregnant women as compared to no screening, we developed a Markov model. For the parameters of the model, we used prevalence data from pregnant women retrospectively tested for HCV in Amsterdam, the Netherlands, and from literature sources. In addition, we estimated the effect of possible treatment improvement in the future. Results The incremental costs per woman screened was €41 and 0.0008 life-years were gained. The incremental cost-effectiveness ratio (ICER) was €52,473 which is above the cost-effectiveness threshold of €50,000. For screening first-generation non-Western migrants, the ICER was €47,113. Best-case analysis for both scenarios showed ICERs of respectively €19,505 and €17,533. We estimated that if costs per treatment were to decline to €3,750 (a reduction in price of €31,000), screening all pregnant women would be cost-effective. Conclusions Currently, adding HCV screening to the already existing screening program for pregnant women is not cost-effective for women in general. However, adding HCV screening for first-generation non-Western women shows a modest cost-effective outcome. Yet, best case analysis shows potentials for an ICER below €20,000 per life-year gained. Treatment options will improve further in the coming years, enhancing cost-effectiveness even more.

Mortality rates in people dually infected with HIV-1/2 and those infected with either HIV-1 or HIV-2: a systematic review and meta-analysis.

Objective:As compared to HIV-1 infection, HIV-2 is less transmissible, disease progression is slower, and the mortality risk is lower. It has been suggested that HIV-2 infection inhibits the progression of HIV-1 in individuals dually infected by HIV-1 and HIV-2 (HIV-D). We examined whether the mortality rates in dually infected individuals differ from those in persons infected with either HIV-1 or HIV-2. Design:We conducted a systematic review and meta-analysis. Methods:Medline and Embase databases were searched for studies that reported the number of deaths and person-years of observation (PY) for at least two of the three HIV groups (i.e. HIV-1, HIV-2, and HIV-D). Meta-analyses were then performed with random-effects models, estimating combined mortality rate ratios (MRRs). Results:Of the 631 identified titles, six articles were included in the meta-analysis of HIV-D-infected individuals versus HIV-mono-infected persons, and seven were included in the analysis of HIV-1-mono-infected versus HIV-2-mono-infected individuals. The overall MRR of those infected with HIV-D versus HIV-1 was 1.11 [95% confidence interval (CI) 0.95–1.30]. The overall MRR of those infected with HIV-D versus HIV-2 was 1.81 (95% CI 1.43–2.30) and the MRR of those infected with HIV-1 versus HIV-2 was 1.86 (95% CI 1.44–2.39). Conclusion:HIV-2-mono-infected persons have a lower mortality rate than those mono-infected with HIV-1 and those with HIV-D. There is no evidence that HIV-2 delays progression to death in HIV-D-infected individuals.

Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe

BACKGROUND & AIMS Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. METHODS We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. RESULTS At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%. CONCLUSIONS The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. LAY SUMMARY Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment).

Higher Chlamydia trachomatis prevalence in ethnic minorities does not always reflect higher sexual risk behaviour

Background In affluent countries, the prevalence of Chlamydia trachomatis (CT) is often higher in certain ethnic minorities than in the majority population. In the Netherlands, we examined why CT prevalence is higher in Surinamese/Antilleans, the largest minority in the country. Methods Heterosexuals were recruited for a cross-sectional survey from May through August 2010 at the sexually transmitted infections (STI) clinic in Amsterdam. Participants completed a questionnaire and were tested for STI. A causal directed acyclic graph was assumed to investigate whether the association between ethnicity and CT could be explained by differences in sexual risk behaviour and socio-economic status. Results Subjects included 1044 with Dutch background and 335 with Surinamese/Antillean background. Median age for the combined population was 25 (IQR 22-30) years, and 55.4% was female. Sexual risk behaviour did not differ significantly between the two groups. CT was diagnosed in 17.9% of Surinamese/Antilleans and in 11.4% of Dutch. Surinamese/Antilleans were significantly more likely to have CT (OR 1.70; 95% CI 1.21-2.38). The association between ethnicity and CT remained statistically significant after adjusting for sexual risk behaviour, age, sex, and ethnic mixing (aOR 1.48; 95% CI 1.00-2.18), but not after adjusting for education and neighbourhood, markers of socio-economic status (aOR 1.08; 95% CI 0.71-1.64). Conclusion The difference in CT prevalence between the minority and majority groups was not explained by differences in sexual risk behaviour. The higher CT prevalence found among Surinamese/Antilleans appeared to reflect their lower educational level and neighbourhood, two markers of lower socio-economic status. We hypothesise that the effect results from lower health-seeking behaviour.

Cost-Effectiveness of Hepatitis C Treatment for People Who Inject Drugs and the Impact of the Type of Epidemic; Extrapolating from Amsterdam, the Netherlands

Background People who inject drugs (PWID) are disproportionally affected by the hepatitis C virus (HCV) infection. The efficacy of HCV treatment has significantly improved in recent years with the introduction of direct-acting antivirals (DAAs). However, DAAs are more costly than pegylated-interferon and ribavirin (PegIFN/RBV). We aimed to assess the cost-effectiveness of four HCV treatment strategies among PWID and treatment scale-up. Methods An individual-based model was used describing HIV and HCV transmission and disease progression among PWID. We considered two epidemiological situations. A declining epidemic, based on the situation in Amsterdam, the Netherlands, and a stable HCV epidemic, as observed in other settings. Data on HCV incidence, prevalence, treatment setting and uptake were derived from observed data among PWID in Amsterdam. We assessed the incremental cost-effectiveness ratio (ICER, costs in €/quality-adjusted life year (QALY)) of four treatment strategies: 1) PegIFN/RBV; 2) sofosbuvir/RBV for genotype 2–3 and dual DAA for genotype 1–4; 3) Dual DAA for all genotypes; 4) Dual DAA with 3x treatment uptake. Results In both types of epidemic, dual DAA therapy was most cost-effective strategy. In the declining epidemic, dual DAA yielded an ICER of 344 €/QALY while in the stable epidemic dual DAA led to cost-savings. Scaling-up treatment was also highly cost-effective. Our results were robust over a range of sensitivity analyses. Conclusion HCV treatment with DAA-containing regimens is a highly cost-effective intervention among PWID. Based on the economic and population benefits of scaling-up treatment, stronger efforts are needed to achieve higher uptake rates among PWID.