Sharp increase in gonorrhoea notifications among young people, EU/EEA, July 2022 to June 2023.

Gonorrhoea cases increased steeply in women aged 20 to 24 years across 15 EU/EEA countries in July to December 2022 and January to June 2023 with, respectively, 73% and 89% more cases reported than expected, based on historical data from 2015 to 2019. Smaller increases among men due to heterosexual transmission were observed in nine EU/EEA countries. Interventions to raise awareness among young people about sexually transmitted infection risks are needed, emphasising the benefit of safe sexual practices and testing.

Increased risk of subsequent chlamydia infection among women not tested at the anorectal anatomical location.

BACKGROUND: Universal anorectal testing for Chlamydia trachomatis (chlamydia) among women is not recommended in many countries, while anorectal chlamydia infections are common. Missed anorectal infections might cause sequelae at the genital site if autoinoculation from the anorectum is possible, but evidence is limited. This study investigates the association between potentially missed anorectal infections and subsequent genital chlamydia infections in women, using not being tested at the anorectal site as a proxy for having a potentially missed anorectal infection. METHODS: We included all women with a repeat chlamydia test within 1 year (with at least a genital test) from the Dutch sexual health centre surveillance between 2014 and 2019. Multilevel logistic regression analyses were used to identify determinants of genital chlamydia infection at the repeat test, with anorectal testing at the previous chlamydia test as the main determinant. RESULTS: A total of 40 217 women were included in the analyses, of whom 15.4% tested chlamydia-positive genitally at their second test. Not being tested anorectally at the first test was an independent risk factor for genital chlamydia infection at the repeat test (adjusted OR 1.24, 95% CI 1.15 to 1.33). This association was in the same range as most other significant risk factors in the model: low education level, no condom use, STI symptoms and previous STI diagnosis. Young age (<20 years) (2.67, 2.39-2.98) and those who received partner notification (3.11, 2.91-3.31) showed stronger associations. The findings were robust; correcting for interactions and a sensitivity analysis stratifying by chlamydia infection at first visit did not show significant differences in the adjusted OR of not being tested anorectally at first test. CONCLUSION: The results are suggestive of an autoinoculation process from the anorectal to the genital anatomical site in women. To enhance chlamydia control, future studies on the role of extragenital testing and autoinoculation in chlamydia transmission are needed.

Trends and regional variations of gonococcal antimicrobial resistance in the Netherlands, 2013 to 2019.

BackgroundGonococcal antimicrobial resistance is emerging worldwide and is monitored in the Netherlands in 18 of 24 Sexual Health Centres (SHC).AimTo report trends, predictors and regional variation of gonococcal azithromycin resistance (AZI-R, minimum inhibitory concentration (MIC) > 1 mg/L) and ceftriaxone decreased susceptibility (CEF-DS, MIC > 0.032 mg/L) in 2013-2019.MethodsSHC reported data on individual characteristics, sexually transmitted infection diagnoses, and susceptibility testing (MIC, measured by Etest). We used multilevel logistic regression analysis to identify AZI-R/CEF-DS predictors, correcting for SHC region. Population differences' effect on regional variance of AZI-R and CEF-DS was assessed with a separate multilevel model.ResultsThe study included 13,172 isolates, predominantly (n = 9,751; 74%) from men who have sex with men (MSM). Between 2013 and 2019, annual proportions of AZI-R isolates appeared to increase from 2.8% (37/1,304) to 9.3% (210/2,264), while those of CEF-DS seemed to decrease from 7.0% (91/1,306) to 2.9% (65/2,276). Among SHC regions, 0.0‒16.9% isolates were AZI-R and 0.0-7.0% CEF-DS; population characteristics could not explain regional variance. Pharyngeal strain origin and consultation year were significantly associated with AZI-R and CEF-DS for MSM, women, and heterosexual men. Among women and heterosexual men ≥ 4 partners was associated with CEF-DS, and ≥ 10 with AZI-R.ConclusionsNo resistance or decreasing susceptibility was found for CEF, the first line gonorrhoea treatment in the Netherlands. Similar to trends worldwide, AZI-R appeared to increase. Regional differences between SHC support nationwide surveillance with regional-level reporting. The increased risk of resistance/decreased susceptibility in pharyngeal strains underlines the importance of including extragenital infections in gonococcal resistance surveillance.

Low gonorrhoea antimicrobial resistance and culture positivity rates in general practice: a pilot study.

OBJECTIVE: In the Netherlands, the Gonococcal Resistance to Antimicrobials Surveillance (GRAS) programme is carried out at Centres for Sexual Health (CSH), which provide care for sexual high-risk populations. However, half of gonorrhoea infections are diagnosed in general practice (GP). We performed a pilot study to explore expanding GRAS to GPs using laboratory-based surveillance. Additionally, antimicrobial resistance patterns of GP and CSH patients were compared. METHODS: Three laboratories from different regions were included, which all perform gonorrhoea diagnostics for GPs and used ESwab for patient sampling. Additional culturing for all GP patients with gonorrhoea took place from February to July 2018. After positive PCR-nucleic acid amplification test, residual ESwab material was used for culture. In positive cultures, susceptibility testing was performed for azithromycin, ciprofloxacin, cefotaxime and ceftriaxone using Etest. RESULTS: During the study period, 484 samples were put in culture. 16.5% of cultures were positive (n=80). Antimicrobial resistance levels were low, with 2.6% resistance to azithromycin, 21.5% to ciprofloxacin and 0.0% to cefotaxime and ceftriaxone. Resistance levels in CSH GRAS data (first half of 2018) were 19.2% for azithromycin, 31.5% for ciprofloxacin, 1.9% for cefotaxime and 0.0% for ceftriaxone. CONCLUSIONS: Culture positivity rates for GP patients were low, probably due to long transportation times and awaiting PCR test results before attempting culture. Positivity rates might be improved by making changes in sampling and/or transportation methods, but that would require involvement of GPs and patients instead of keeping the surveillance lab based. Resistance levels appeared to be lower at GPs than at the CSH, indicating that resistance might emerge first in more high-risk populations. It is important to consider all potentially relevant patient populations when establishing a gonococcal antimicrobial resistance surveillance programme. However, based on the findings from this study the current GRAS programme will not be extended to GPs.

Impact of frequent testing on the transmission of HIV and N. gonorrhoeae among men who have sex with men: a mathematical modelling study.

OBJECTIVES: To investigate the impact and efficiency of combined testing for HIV and other STIs on HIV and STI transmission among men who have sex with men (MSM) and to assess what subgroups of MSM should be targeted for frequent testing. METHODS: We developed an agent-based transmission model that simulates infection with HIV or Neisseria gonorrhoeae (NG) among MSM. We examined scenarios with increased percentages of MSM getting tested six monthly, among all MSM or only specific subgroups of MSM (defined according to recent gonorrhoea, number of partners and engagement in condomless anal intercourse (CAI)) and scenarios with reduced intervals between HIV/STI tests. RESULTS: The most efficient strategies were those with increased percentage of MSM getting tested every 6 months among MSM with a recent gonorrhoea diagnosis; or among MSM who had CAI and ≥10 partners; or MSM who had ≥10 partners. Over 10 years, these strategies resulted in 387-718 averted HIV infections and required 29-164 additional HIV tests per averted HIV infection or one to seven additional gonorrhoea tests per averted NG infection. The most effective strategy in reducing HIV transmission was the one where the intervals between tests were reduced by half, followed by the strategy with increased percentage of MSM getting tested every 6 months among all MSM. Over 10 years, these strategies resulted in 1362 and 1319 averted HIV infections, but required 663 and 584 additional HIV tests per averted HIV infection, respectively. CONCLUSIONS: Targeting MSM with recent gonorrhoea diagnosis or MSM with many partners is efficient in terms of HIV/STI tests needed to prevent new HIV or NG infections. Major reductions in HIV incidence can be achieved with consistent HIV/STI testing every 6 months among larger groups, including low-risk MSM. To impede HIV transmission, frequent testing should be combined with other prevention measures.

Evaluating progress towards triple elimination of mother-to-child transmission of HIV, syphilis and hepatitis B in the Netherlands.

BACKGROUND: In 2014 the World Health Organisation (WHO) established validation criteria for elimination of mother-to-child transmission (EMTCT) of HIV and syphilis. Additionally, the WHO set targets to eliminate hepatitis, including hepatitis B (HBV). We evaluated to what extent the Netherlands has achieved the combined WHO criteria for EMTCT of HIV, syphilis and HBV. METHODS: Data of HIV, syphilis and HBV infections among pregnant women and children (born in the Netherlands with congenital infection) for 2009-2015, and data required to validate the WHO criteria were collected from multiple sources: the antenatal screening registry, the HIV monitoring foundation database, the Perinatal Registry of the Netherlands, the national reference laboratory for congenital syphilis, and national HBV notification data. RESULTS: Screening coverage among pregnant women was > 99% for all years, and prevalence of HIV, syphilis and HBV was very low. In 2015, prevalence of HIV, syphilis and HBV was 0.06, 0.06 and 0.29%, respectively. No infections among children born in the Netherlands were reported in 2015 for all three diseases, and in previous years only sporadic cases were observed In 2015, treatment of HIV positive pregnant women was 100% and HBV vaccination of children from HBV positive mothers was > 99%. For syphilis, comprehensive data was lacking to validate WHO criteria. CONCLUSIONS: In the Netherlands, prevalence of maternal HIV, syphilis and HBV is low and congenital infections are extremely rare. All minimum WHO criteria for validation of EMTCT are met for HIV and HBV, but for syphilis more data are needed to prove elimination.

A pill for the partner via the chlamydia patient? Results from a mixed method study among sexual health care providers in the Netherlands.

BACKGROUND: Chlamydia prevalence in the Netherlands remains high despite targeted efforts. Effective Partner Notification (PN) and Partner Treatment (PT) can interrupt transmission and prevent re-infections. Patient Initiated Partner Treatment (PIPT) may strengthen chlamydia control. This study explores the current practice of PN and PT, and benefits of, and barriers and facilitators for PIPT among professionals in sexual health care in the Netherlands. METHODS: A qualitative study was performed among GPs, GP-assistants (GPAs), physicians and nurses working at Sexual Health Clinics (SHC) and key-informants on ethnical diversity using topic lists in focus groups (N = 40) and semi-structured questionnaires in individual interviews (N = 9). Topics included current practices regarding PN and PT, attitude regarding PIPT, and perceived barriers and facilitators for PIPT. Interviews were taped, transcribed verbatim, and coded using ATLAS.ti. A quantitative online questionnaire on the same topics was sent to all physicians and nurses employed at Dutch SHC (complete response rate 26% (84/321)). RESULTS: The qualitative study showed that all professionals support the need for more attention to PN, and that they saw advantages in PIPT. Mentioned barriers included unwilling PN-behaviour, Dutch legislation, several medical considerations and inadequate skills of GPs. Also, concerns about limited knowledge of cultural sensitivity around PN and PT were raised. Mentioned facilitators of PIPT were reliable home based test-kits, phone-contact between professionals and notified partners, more consultation time for GPs or GPAs and additional training. The online questionnaire showed that SHC employees agreed that partners should be treated as soon as possible, but also that they were reluctant towards PIPT without counselling and testing. CONCLUSIONS: Professionals saw advantages in PIPT, but they also identified barriers hampering the potential introduction of PIPT. Improving PN and counselling skills with specific focus on cultural sensitivity is needed. PIPT could be considered for specific partners. PIPT in combination with home based testing and using e-healthcare should be further explored and developed.

Frequency and determinants of consistent STI/HIV testing among men who have sex with men testing at STI outpatient clinics in the Netherlands: a longitudinal study.

OBJECTIVES: Men who have sex with men (MSM) are at highest risk for STIs and HIV infections in the Netherlands. However, official guidelines on STI testing among MSM are lacking. They are advised to test for STIs at least every six months, but their testing behaviour is not well known. This study aimed to get insight into the proportion and determinants of consistent 6-monthly STI testing among MSM testing at STI outpatient clinics in the Netherlands. METHODS: This study included longitudinal surveillance data of STI consultations among MSM from all 26 STI outpatient clinics in the Netherlands between 1 June 2014 and 31 December 2015. Multinomial logistic regression analysis was used to identify determinants of consistent 6-monthly testing compared with single testing and inconsistent testing. Determinants of time between consultations among men with multiple consultations were analysed using a Cox Prentice-Williams-Peterson gap-time model. RESULTS: A total of 34 605 STI consultations of 18 634 MSM were included. 8966 (48.1%) men had more than one consultation, and 3516 (18.9%) men tested consistently 6-monthly. Indicators of high sexual risk behaviour, including having a history of STI, being HIV positive and having more than 10 sex partners, were positively associated with both being a consistent tester and returning to the STI clinic sooner. Men who were notified by a partner or who reported STI symptoms were also more likely to return to the STI clinic sooner, but were less likely to be consistent testers, identifying a group of event-driven testers. CONCLUSIONS: The proportion of consistent 6-monthly testers among MSM visiting Dutch STI outpatient clinics was low. Testing behaviour was associated with sexual risk behaviour, but exact motives to test consistently remain unclear. Evidence-based testing guidelines are needed to achieve optimal reductions in STI transmission in the future.

Repeat Chlamydia trachomatis testing among heterosexual STI outpatient clinic visitors in the Netherlands: a longitudinal study.

BACKGROUND: Chlamydia infections are common in both men and women, are often asymptomatic and can cause serious complications. Repeat testing in high-risk groups is therefore indicated. In the Netherlands, guidelines on repeat chlamydia testing differ between testing facilities, and knowledge on repeat testing behaviour is limited. Here, we analyse the current repeat testing behaviour of heterosexual STI clinic visitors, and aim to identify groups for which repeat testing advice could be advantageous. METHODS: Longitudinal surveillance data from all Dutch STI outpatient clinics were used, which included all STI clinic consultations carried out among heterosexual men and women between June 2014 and December 2015. Repeat testing was defined as returning to the same STI clinic between 35 days and 12 months after initial consultation. We calculated chlamydia positivity at repeat test stratified by initial test result and time between consultations. Logistic regression analyses were used to identify predictors of repeat testing, and predictors of having a chlamydia positive repeat test. RESULTS: In total, 140,486 consultations in 75,487 women and 46,286 men were available for analyses. Overall, 15.4% of women and 11.1% of men returned to the STI clinic within the study period. Highest chlamydia positivity at repeat test was seen 3-5 months after initial positive test. Among both women and men, repeat testing was associated with non-Western ethnicity, having had more than two sex partners in the past 6 months, reporting STI symptoms, having a history of STI, and having a chlamydia positive initial test. Among repeat testers, chlamydia positive repeat test was most strongly associated with younger age, followed by a chlamydia positive initial test. CONCLUSIONS: Repeat testing most often resulted in a positive test result among young heterosexuals (<25) and heterosexuals of any age with a chlamydia infection at the initial consultation. Further efforts are needed to determine optimal repeat testing strategies.

Antisense oligonucleotides for the treatment of dyslipidaemia.

Antisense oligonucleotides (ASOs) are short synthetic analogues of natural nucleic acids designed to specifically bind to a target messenger RNA (mRNA) by Watson-Crick hybridization, inducing selective degradation of the mRNA or prohibiting translation of the selected mRNA into protein. Antisense technology has the ability to inhibit unique targets with high specificity and can be used to inhibit synthesis of a wide range of proteins that could influence lipoprotein levels and other targets. A number of different classes of antisense agents are under development. To date, mipomersen, a 2'-O-methoxyethyl phosphorothioate 20-mer ASO, is the most advanced ASO in clinical development. It is a second-generation ASO developed to inhibit the synthesis of apolipoprotein B (apoB)-100 in the liver. In Phase 3 clinical trials, mipomersen has been shown to significantly reduce plasma low-density lipoprotein cholesterol (LDL-c) as well as other atherogenic apoB containing lipoproteins such as lipoprotein (a) [Lp(a)] and small-dense LDL particles. Although concerns have been raised because of an increase in intrahepatic triglyceride content, preliminary data from long-term studies suggest that with continued treatment, liver fat levels tend to stabilize or decline. Further studies are needed to evaluate potential clinical relevance of these changes. Proprotein convertase subtilisin/kexin-9 (PCSK9) is another promising novel target for lowering LDL-c by ASOs. Both second-generation ASOs and ASOs using locked nucleic acid technology have been developed to inhibit PCSK9 and are under clinical development. Other targets currently being addressed include apoC-III and apo(a) or Lp(a). By directly inhibiting the synthesis of specific proteins, ASO technology offers a promising new approach to influence the metabolism of lipids and to control lipoprotein levels. Its application to a wide variety of potential targets can be expected if these agents prove to be clinically safe and effective.

Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial.

AIMS: A randomized, double-blind, placebo-controlled study was conducted to investigate the safety and efficacy of mipomersen, an apolipoprotein B-100 (apoB) synthesis inhibitor, in patients who are statin intolerant and at high risk for cardiovascular disease (CVD). METHODS AND RESULTS: Thirty-three subjects, not receiving statin therapy because of statin intolerance, received a weekly subcutaneous dose of 200 mg mipomersen or placebo (2:1 randomization) for 26 weeks. The primary endpoint was per cent change in LDL cholesterol (LDL-c) from the baseline to Week 28. The other efficacy endpoints were per cent change in apoB and lipoprotein a [Lp(a)]. Safety was determined using the incidence of treatment-emergent adverse events (AEs) and clinical laboratory evaluations. After 26 weeks of mipomersen administration, LDL-c was reduced by 47 ± 18% (P < 0.001 vs. placebo). apoB and Lp(a) were also significantly reduced by 46 and 27%, respectively (P < 0.001 vs. placebo). Four mipomersen (19%) and two placebo subjects (17%) discontinued dosing prematurely due to AEs. Persistent liver transaminase increases ≥ 3× the upper limit of normal were observed in seven (33%) subjects assigned to mipomersen. In selected subjects, liver fat content was assessed, during and after treatment, using magnetic resonance spectroscopy. Liver fat content in these patients ranged from 0.8 to 47.3%. Liver needle biopsy was performed in two of these subjects, confirming hepatic steatosis with minimal inflammation or fibrosis. CONCLUSION: The present data suggest that mipomersen is a potential therapeutic option in statin-intolerant patients at high risk for CVD. The long-term follow-up of liver safety is required. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00707746.

HIV and syphilis testing for women and heterosexual men aged above 25 years in the Netherlands: possibilities for targeted testing at sexual health centres.

OBJECTIVES: Targeted testing policy for HIV/syphilis at Dutch sexual health centres (SHCs) was evaluated for its efficiency in younger heterosexuals but not for heterosexuals ≥25 years. Currently, all older heterosexuals are tested for HIV/syphilis at SHCs. To explore possibilities for increased efficiency of testing in heterosexuals aged >25 years, this study aimed to identify determinants of HIV and syphilis diagnoses that could be used in targeted testing strategies. DESIGN: An observational study using surveillance data from all Dutch SHC. PARTICIPANTS: Women and heterosexual men aged >25 years visiting SHC between 2015 and 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was HIV/syphilis diagnosis, determinants of a diagnosis were analysed. Based on these determinants and their applicability in SHC practice, different targeted testing scenarios were evaluated. For each scenario, the percentage of consultations involving HIV and syphilis testing and the total amount of missed HIV and syphilis diagnoses were calculated. RESULTS: 109 122 consultations were included among 75 718 individuals. The strongest determinants of HIV/syphilis diagnosis were HIV/syphilis-specific symptoms (adjusted OR (aOR) 34.9 (24.1-50.2)) and receiving partner notification (aOR 18.3 (13.2-25.2)), followed by low/middle education level (aOR 2.8 (2.0-4.0)), male sex (aOR 2.2 (1.6-3.0)) and age ≥30 years (aOR 1.8 (1.3-2.5)). When applying feasible determinants to targeted testing scenarios, HIV/syphilis testing would have been conducted in 54.5% of all consultations, missing 2 HIV and 3 syphilis diagnoses annually (13.4% and 11.4% of all diagnoses, respectively). In the scenario with the lowest number of missed HIV/syphilis diagnoses (0.3 HIV and 2 syphilis diagnoses annually), HIV/syphilis testing would have been conducted in 74.2% of all consultations. CONCLUSIONS: In any targeted testing scenario studied, HIV and/or syphilis diagnoses would have been missed. This raises the question whether it is acceptable to put any of these scenarios into practice. This study contributes to a discussion about the impact of targeted testing policy.

An increased burden of common and rare lipid-associated risk alleles contributes to the phenotypic spectrum of hypertriglyceridemia.

OBJECTIVE: Earlier studies have suggested that a common genetic architecture underlies the clinically heterogeneous polygenic Fredrickson hyperlipoproteinemia (HLP) phenotypes defined by hypertriglyceridemia (HTG). Here, we comprehensively analyzed 504 HLP-HTG patients and 1213 normotriglyceridemic controls and confirmed that a spectrum of common and rare lipid-associated variants underlies this heterogeneity. METHODS AND RESULTS: First, we demonstrated that genetic determinants of plasma lipids and lipoproteins, including common variants associated with plasma triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from the Global Lipids Genetics Consortium were associated with multiple HLP-HTG phenotypes. Second, we demonstrated that weighted risk scores composed of common TG-associated variants were distinctly increased across all HLP-HTG phenotypes compared with controls; weighted HDL-C and LDL-C risk scores were also increased, although to a less pronounced degree with some HLP-HTG phenotypes. Interestingly, decomposition of HDL-C and LDL-C risk scores revealed that pleiotropic variants (those jointly associated with TG) accounted for the greatest difference in HDL-C and LDL-C risk scores. The APOE E2/E2 genotype was significantly overrepresented in HLP type 3 versus other phenotypes. Finally, rare variants in 4 genes accumulated equally across HLP-HTG phenotypes. CONCLUSIONS: HTG susceptibility and phenotypic heterogeneity are both influenced by accumulation of common and rare TG-associated variants.

The impact of the COVID-19 pandemic on hepatitis B virus vaccination and transmission among men who have sex with men: A mathematical modelling study.

BACKGROUND: During the COVID-19 pandemic, the number of hepatitis B virus (HBV) vaccinations among men who have sex with men (MSM) has been considerably lower than before the pandemic. Moreover, less frequent HBV testing and a reduction in numbers of sex partners have been reported. We assessed the impact of these COVID-19-related changes on HBV transmission among MSM in the Netherlands. METHODS: We estimated the changes in sexual activity, HBV testing, and HBV vaccination among MSM during the pandemic from Dutch data. We used a deterministic compartmental model and investigated scenarios with small or large declines in sexual activity, testing, and vaccination for the current phase of the pandemic (without available data). We examined the increase in HBV vaccinations needed to prevent further increase in HBV incidence. RESULTS: With a decrease in numbers of sex partners of 15-25% during the first lockdown and 5% during the second lockdown, we found a decline of 6.6% in HBV incidence in 2020, despite a >70% reduction in HBV testing and vaccination during the first lockdown. With numbers of sex partners rebounding close to pre-pandemic level in 2021, and a reduction of 15% in testing and 30% in vaccination in 2021, we found an increase of 1.4% in incidence in 2021 and 3.1% in 2026. With these changes, an increase of ≥60% in HBV vaccinations in 2022 would be needed to bring the HBV incidence in 2023 back to the level that it would have had if the COVID-19-related changes had not occurred. CONCLUSIONS: Despite reductions in sexual activity during the COVID-19 pandemic, the decrease in HBV vaccinations may result in a small increase in HBV incidence after 2021, which may persist for years. It is important to restore the vaccination level and limit further increase in HBV transmission among MSM.

Apolipoprotein B synthesis inhibition: results from clinical trials.

PURPOSE OF REVIEW: Mipomersen is a second-generation antisense oligonucleotide developed to inhibit the synthesis of apolipoprotein B-100 in the liver. In this review we will summarize the results of recent preclinical and clinical studies addressing safety and low-density lipoprotein-cholesterol (LDL-c) lowering efficacy of this new compound. RECENT FINDINGS: In phase 3 clinical trials, mipomersen has been shown to significantly reduce LDL-c in patients with homozygous and heterozygous familial hypercholesterolemia on maximally tolerated lipid-lowering therapy. Injection site reactions, flu-like symptoms and increases in liver transaminases were the main adverse events. A recent safety study, designed to investigate the effects of mipomersen on intrahepatic triglyceride content, failed to show evidence of clinically relevant hepatic steatosis after 13 weeks of treatment. SUMMARY: Mipomersen is a new agent to lower LDL-c in patients at increased risk of cardiovascular disease and/or intolerant to statins. Whereas safety concerns have focused on hepatic fat accumulation, to date no evidence of clinically relevant increases of intrahepatic triglyceride content are reported. Ongoing and future studies are eagerly awaited to assess the impact of mipomersen on hepatic triglyceride content after prolonged exposure.

Ending risk-group HBV vaccination for MSM after the introduction of universal infant HBV vaccination: A mathematical modelling study.

BACKGROUND: Risk-group HBV vaccination for men who have sex with men (MSM) was introduced in the Netherlands in 2002, followed by universal infant vaccination in 2011, that will enable termination of risk-group vaccination over time. The introduction of pre-exposure prophylaxis (PrEP) for HIV prevention might result in increased HBV testing and vaccination against HBV. The aim of this study was to investigate the impact of the transition from risk-group to universal HBV vaccination, accounting for improvements in HBV testing and treatment, as well as the introduction of PrEP. METHODS: We developed a mathematical model for HBV transmission among MSM. Universal vaccination was modelled by assigning some MSM (5-15% in 2028 increasing to 80-90% in 2033 and thereafter) to be vaccinated when they become sexually active. We investigated different scenarios assuming 0.5% extra vaccination rate and 0.5% extra testing rate due to PrEP consultations; and 5% of HIV-negative MSM on PrEP, that will reduce the probability of HBV acquisition by 88%. RESULTS: Universal vaccination resulted in a reduction of 24% (interquartile range; 22-25%) of the total number of HBV infections among MSM estimated to occur from 2020 to 2070. With universal vaccination, terminating risk-group vaccination in 2030 or 2040 resulted in 30% or 10% more HBV infections over 2020-2070, respectively, compared to continuation of risk-group vaccination until 2070. With PrEP and continued risk-group vaccination, the total number of HBV infections over 2020-2070 was reduced by 13%. CONCLUSIONS: Universal HBV vaccination can lead to a major reduction in HBV incidence among MSM in the future. The reduction becomes smaller when ending risk-group HBV vaccination, but larger by PrEP use for HIV prevention. Efforts to keep high levels of HBV vaccination, testing, and treatment have to be continued in the coming decades in order to eliminate HBV as a health threat for MSM.

Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia.

To investigate the impact of mipomersen, an apolipoprotein B-100 (apoB) synthesis inhibitor, on intra-hepatic triglyceride content (IHTG content), we conducted a randomized, double-blind, placebo-controlled study in 21 patients with familial hypercholesterolemia (FH). Subjects received a weekly subcutaneous dose of 200 mg mipomersen or placebo for 13 weeks while continuing conventional lipid lowering therapy. The primary endpoint was change in IHTG content from week 0 to week 15 as measured by localized proton magnetic resonance spectroscopy (1H-MRS). Thirteen weeks of mipomersen administration reduced LDL-cholesterol by 22.0 (17.8) % and apoB by 19.9 (17.4) % (both P < 0.01). One of 10 patients (10%) in the mipomersen-treated group developed mild hepatic steatosis at week 15, which was reversible following mipomersen discontinuation. For the group, there was a trend toward an increase in IHTG content [placebo; baseline: 1.2% and week 15: 1.1%; change -0.1 (0.9). Mipomersen; baseline: 1.2% and week 15: 2.1%; change 0.8 (1.7) (P = 0.0513)]. Mipomersen administration for 13 weeks to subjects with FH is associated with a trend toward an increase in IHTG content. Future studies evaluating the effects of long-term use of mipomersen reaching more profound reductions in apoB are required prior to broader use of this compound.

Hepatitis B and C screening needs among different ethnic groups: A population-based study in Amsterdam, the Netherlands.

Data on the prevalence of chronic hepatitis B (HBV) and hepatitis C (HCV) virus infections, including the proportion of individuals aware of infection, are scarce among migrants living in Europe. We estimated the prevalence of past and present HBV and HCV infection, along with their determinants and peoples' awareness of infection status, among different groups of first-generation migrants and Dutch-origin residents of Amsterdam. METHODS: Cross-sectional data of 998 Surinamese (mostly South-Asian and African-Surinamese), 500 Ghanaian, 497 Turkish, 498 Moroccan and 500 Dutch-origin participants from the observational population-based HELIUS study were used. Blood samples of participants were tested for HBV and HCV infection. Infection awareness was determined using records from participants' general practitioners. RESULTS: Age- and gender-adjusted chronic HBV prevalence was highest among Ghanaian participants (5.4%), followed by Turkish (4.1%), African-Surinamese (1.9%), Moroccan (1.2%), South-Asian Surinamese (0.9%) and Dutch (0.4%) participants. A total of 58.1% of the cases were aware of their infection. In multinomial logistic regression analyses, Ghanaian (adjusted odds ratio [aOR] 42.23; 95% confidence interval [CI] 9.29-192.01), African-Surinamese (aOR 6.16; 95% CI 1.27-29.79), and Turkish (aOR 13.44; 95% CI 2.94-61.39) participants were at increased risk of chronic HBV infection compared with those of Dutch origin. Older participants were also at increased risk (aOR 1.02 per year; 95% CI 1.00-1.05), whereas women were at lower risk (aOR 0.49; 95% CI 0.29-0.83). HCV prevalence was 0.4% (95% CI 0.1-1.3%) among Dutch and African-Surinamese and 0% (95% CI 0.0-0.5%) for each of the other groups; all cases with follow-up data were aware of their infection. CONCLUSIONS: Ghanaian, Turkish and African-Surinamese first-generation migrants are at increased risk of chronic HBV infection and many are unaware of their infection, whereas HCV prevalence was low among all ethnic groups. Screening campaigns are urgently warranted and need to consider specific ethnic groups. LAY SUMMARY: First-generation migrants of Ghanaian, Turkish and African-Surinamese origin were at increased risk of chronic hepatitis B infection, with most infections occurring in older individuals and males. Since over 40% of people were unaware of their chronic hepatitis B infection, screening of these migrant groups is urgently needed. The proportion of first-generation migrants chronically infected with hepatitis C virus was very low among all groups studied.

Cost-effectiveness of increased HIV testing among MSM in The Netherlands.

OBJECTIVES: To assess the cost-effectiveness of increased consistent HIV testing among MSM in the Netherlands. METHODS: Among MSM testing at sexually transmitted infection clinics in the Netherlands in 2014-2015, approximately 20% tested consistently every 6 months. We examined four scenarios with increased percentage of MSM testing every 6 months: a small and a moderate increase among all MSM; a small and a moderate increase only among MSM with at least 10 partners in the preceding 6 months. We used an agent-based model to calculate numbers of HIV infections and AIDS cases prevented with increased HIV testing. These numbers were used in an economic model to calculate costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) due to increased testing, over 2018-2027, taking a healthcare payer perspective. RESULTS: A small increase in the percentage testing every 6 months among all MSM resulted in 490 averted HIV infections and an average ICER of &OV0556;27 900/QALY gained. A moderate increase among all MSM, resulted in 1380 averted HIV infections and an average ICER of &OV0556;36 700/QALY gained. Both were not cost-effective, with a &OV0556;20 000 willingness-to-pay threshold. Increasing the percentage testing every 6 months only among MSM with at least 10 partners in the preceding 6 months resulted in less averted HIV infections than increased testing among all MSM, but was on average cost-saving. CONCLUSION: Increased HIV testing can prevent considerable numbers of new HIV infections among MSM, but may be cost-effective only if targeted at high-risk individuals, such as those with many partners.

LDL-C-lowering therapy: current and future therapeutic targets.

Recent trials have emphasized that more intensive low-density lipoprotein cholesterol (LDL-C) lowering results in a further reduction in cardiovascular disease risk. Uptitration of statins has limited incremental LDL-C-lowering effects and leads to an increased incidence of side effects. Therefore, attention has shifted toward alternative LDL-C-lowering modalities. Several promising compounds have entered the clinical trial arena, although with mixed results. Acyl-coenzyme A: cholesterol O-acyltransferase (ACAT) inhibitors failed to show benefit. Microsomal triglyceride transfer protein and squalene synthase inhibitors, in spite of beneficial lipid profile changes, have shown adverse event profiles. In contrast, inhibitors of intestinal cholesterol absorption have shown LDL-C-lowering efficacy associated with few side effects. The inhibition of apolipoprotein B100 synthesis by antisense oligonucleotides has now been tested in phase 2 clinical trials, with promising results. Finally, compounds modifying protein convertase subtilisin/kexin type 9 levels are currently in the preclinical phase. In the present article, we discuss these LDL-C-lowering strategies.