Summary Background miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect ...of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. Methods In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1). We enrolled men and postmenopausal or hysterectomised women (aged 18–65 years) with chronic HCV genotype 1, 3, or 4 infection diagnosed at least 24 weeks before screening who were either treatment naive to or relapsed after interferon-α based therapy. Patients with co-infection (hepatitis B virus or HIV infection), evidence of decompensated liver disease, or a history of hepatocellular carcinoma were excluded. Randomisation was done by an independent, unblinded, statistician using the SAS procedure Proc Plan. The first cohort received one subcutaneous injection of 2 mg/kg RG-101 or placebo; the second cohort received one subcutaneous injection of 4 mg/kg or placebo. Patients were followed up for 8 weeks (all patients) and up to 76 weeks (patients with no viral rebound and excluding those who were randomised to the placebo group) after randomisation. The primary objective was safety and tolerability of RG-101. This trial was registered with EudraCT, number 2013-002978-49. Findings Between June 4, 2014, and Oct 27, 2014, we enrolled 32 patients with chronic HCV genotype 1 (n=16), 3 (n=10), or 4 (n=6) infections. In the first cohort, 14 patients were randomly assigned to receive 2 mg/kg RG-101 and two patients were randomly assigned to receive placebo, and in the second cohort, 14 patients were randomly assigned to receive 4 mg/kg RG-101 and two patients were randomly assigned to receive placebo. Overall, 26 of the 28 patients dosed with RG-101 reported at least one treatment-related adverse event. At week 4, the median viral load reduction from baseline was 4·42 (IQR 3·23–5·00) and 5·07 (4·19–5·35) log10 IU/mL in patients dosed with 2 mg/kg RG-101 or 4 mg/kg RG-101. Three patients had undetectable HCV RNA levels 76 weeks after a single dose of RG-101. Viral rebound at or before week 12 was associated with the appearance of resistance associated substitutions in miR-122 binding regions in the 5′ UTR of the HCV genome. Interpretation This study showed that one administration of 2 mg/kg or 4 mg/kg RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated anti-miR-122 oligonucleotide, was well tolerated and resulted in substantial viral load reduction in all treated patients within 4 weeks, and sustained virological response in three patients for 76 weeks. Funding Regulus Therapeutics, Inc.
Aim(s)
To understand the experiences of HIV nurses in the context of ambivalence between biomedical treatment advancements and the continuing burden for people living with HIV and negative ...representations of HIV.
Design
An interpretative phenomenological study was conducted using in‐depth interviews.
Methods
Twenty‐one interviews with nurses were conducted between November 2021 and March 2022. A thematic analysis was performed.
Results
Six themes related to the nurses' experiences emerged. Despite effective treatment for most people with HIV, nurses identify patient populations that require additional care. Nurses are flexible in making extra appointments to accommodate complex issues in these patients. Nurses develop a unique relationship with their patients based on trust and empathy, linked to patient's experiences with stigma and discrimination for people with HIV. Nurses perceive their tasks as becoming increasingly complex. There is explicit awareness about the changes in HIV care from acute to chronic care and how this affects nurses' tasks. Nurses continue to differentiate HIV from other chronic conditions.
Conclusion
Biomedical advancements change the organization of HIV care while public health concerns remain and patient population has particular needs due to negative social representations of HIV. Nurses navigate these issues in their everyday care.
Implications for the Profession and/or Patient Care
A potential re‐evaluation of the role of nurses in providing chronic HIV care.
Impact
Our study addresses the roles of HIV nurses as care is shifting towards chronic care models. The unique relationship between nurses and patients is key in understanding the importance of nurses in the care trajectory. These findings impact the institutional role of nurses in HIV treatment centres and the institutional organization of HIV care.
Report Method
The COREQ guideline was used.
Patient or Public Contribution
Amsterdam UMC (AMC) staff, the national organization of HIV Nurses and patient organizations contributed to the study design.
In the Netherlands, hepatitis C virus (HCV) transmission occurs primarily in men who have sex with men (MSM). By early diagnosis and immediate treatment of acute HCV infections, HCV micro‐elimination ...in MSM is within reach. In cooperation with the community affected, we developed an online HCV‐RNA home‐based self‐sampling test service. This service combined online HCV self‐risk assessment with the possibility to test anonymously for HCV‐RNA. The service was available in the Netherlands from February 2018 till December 2020 and was promoted online on various dating sites and offline by community volunteers. Using website user data, test results and an online post‐test user survey, we evaluated the service and user experiences. The website page with information about testing was visited by 3401 unique users, of whom 2250 used the HCV‐risk assessment tool, 152 individuals purchased 194 HCV‐RNA tests, and 104 tests were used, of which 101 gave a conclusive result. The target population of MSM at risk was successfully reached with 44.1% of users receiving the advice to test. The test service had a satisfactory uptake (6.8%, 152/2250), a very high HCV‐RNA positivity rate (10.9%, 11/101) and was considered acceptable and easy to use by most MSM.
We demonstrate that an HCV‐RNA home‐based self‐sampling test service is successful in diagnosing HCV infections among MSM. This service could be a valuable addition to existing sexual healthcare services as it may reach men who are otherwise not tested.
Summary
The introduction of clotting factor concentrates has substantially improved the lives of people with clotting factor deficiencies. Unfortunately, the transmission of blood‐borne viral ...infections through these plasma‐derived products led to a huge epidemic of human immunodeficiency virus and viral hepatitis in people with haemophilia (PWH). In a significant proportion of PWH exposed to these viruses, the ensuing decades‐long chronic infection resulted in excess morbidity and mortality. Fortunately, developments in the safety of blood products, as well as vaccination and highly effective antiviral treatments have improved the prospects of PWH. The present article reviews the background of the viral hepatitis epidemic in PWH, the natural history of hepatitis B and C infections and their long‐term management.
Summary Background Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine prevents HIV infections among men who have sex with men (MSM). PrEP can be given on a daily or intermittent basis. ...Unfortunately, PrEP is not reimbursed in most European countries. Cost-effectiveness analyses of PrEP among MSM in Europe are absent but are key for decision makers to decide upon PrEP implementation. Methods We developed a deterministic mathematical model, calibrated to the well defined Dutch HIV epidemic among MSM, to predict the effect and cost-effectiveness of PrEP. PrEP was targeted to 10% of highly sexually active Dutch MSM over the coming 40 years. Cost-effectiveness ratios were calculated to predict the cost-effectiveness of daily and on-demand PrEP. Cost-effectiveness ratios below €20 000 were considered to be cost-effective in this analysis. Findings Within the context of a stable HIV epidemic, at 80% effectiveness and current PrEP pricing, PrEP can cost as much as €11 000 (IQR 9400–14 100) per quality-adjusted life-year (QALY) gained when used daily, or as little as €2000 (IQR 1300–3000) per QALY gained when used on demand. At 80% effectiveness, daily PrEP can be considered cost-saving if the price of PrEP is reduced by 70%, and on-demand PrEP can be considered cost-saving if the price is reduced by 30–40%. Interpretation PrEP for HIV prevention among MSM in the Netherlands is cost-effective. The use of PrEP is most cost-effective when the price of PrEP is reduced through on-demand use or through availability of generic PrEP, and can quickly be considered cost-saving. Funding None.
Since the advent of direct‐acting antivirals, elimination of hepatitis C viral (HCV) infections seems within reach. However, studies on the HCV cascade of care show suboptimal progression through ...each step for all patient groups. Loss to follow‐up (LTFU) is a major issue and is a barrier to HCV elimination. This review summarizes the scale of the LTFU problem and proposes a micro‐elimination approach. Retrieving LTFU patients and re‐engaging them with care again has shown to be feasible in the Netherlands. Micro‐elimination through retrieval can contribute to reaching the World Health Organization's viral hepatitis elimination targets by 2030.
Since the introduction of effective anti-retroviral therapy, early diagnosis and treatment of HIV have become increasingly important from individual and public health perspectives. People who are ...diagnosed with a CD4 count below 350 cells/µL blood are today considered to be “late” diagnoses. In an effort to understand the reasons for late diagnosis, we conducted in-depth interviews (n = 14) in Amsterdam, the Netherlands. Two main factors were identified: psychosocial factors and health-system factors. Psychosocial factors relate to people’s personal relationship with health professionals, low risk perception, fear related to the outcome of testing, and trauma from observed past experiences of living with HIV. Health-system factors relate to institutional barriers and missed opportunities during client-provider interactions. We conclude that in order to mitigate late diagnosis, the social and institutional context within which HIV testing is conducted should be addressed.
Background: A significant portion of individuals with hepatitis B virus (HBV) or hepatitis C virus (HCV) in the Netherlands remain undiagnosed, with a majority from migrant backgrounds. Objectives: ...This study explored whether targeting HBV/HCV screening among individuals with metabolic risk factors enhances screening efficacy within a diverse ethnic cohort. Methods: Participants from six ethnic backgrounds were enlisted from the population-based, prospective HELIUS study in the Netherlands. Included were participants at elevated risk for non-alcoholic fatty liver disease (NAFLD), identified by elevated non-invasive tests (NITs) and/or metabolic risk factors, who were then tested for HBV/HCV. We evaluated screening efficiency, defined as the prevalence of HBV/HCV, by implementing two targeted screening strategies: (1) Testing individuals with elevated NITs; and (2) those with metabolic risk factors. These strategies were compared to a generic testing approach previously utilized in a subset of HELIUS participants. For non-Dutch origin participants, analyses were stratified based on the HBsAg-prevalence in their region of origin: Low (< 2%) and intermediate (2 - 8%). Results: The study included 346 participants at risk for NAFLD, predominantly of Surinamese (n = 180; 45%), Dutch (n = 103; 26%), or Ghanaian (n = 63; 16%) origin. The generic testing approach encompassed 3,050 individuals. Among individuals from low and intermediate HBV-endemic countries, HBsAg-prevalence was 4.7% and 5.3% for those with elevated NITs, 3.9%, and 3.5% for those with metabolic risk factors, and 0.8% and 3.7% for generic testing, respectively. Regarding HCV, two individuals were anti-HCV-positive, with none being HCV-RNA-positive. Conclusions: Targeted screening based on metabolic risk factors or elevated NITs may be more efficient than generic screening among migrants from regions with low HBV prevalence.
Background and Aims
The path to hepatitis C virus (HCV) elimination is complicated by individuals who become lost to follow‐up (LTFU) during care, particularly before receiving effective HCV ...treatment. We aimed to determine factors contributing to LTFU and whether LTFU is associated with mortality.
Methods
In this secondary analysis, we constructed a database including individuals with HCV who were either LTFU (data from the nationwide HCV retrieval project, CELINE) or treated with directly acting antivirals (DAA) (data from Statistics Netherlands) between 2012 and 2019. This database was linked to mortality data from Statistics Netherlands. Determinants associated with being LTFU versus DAA‐treated were assessed using logistic regression, and mortality rates were compared between groups using exponential survival models. These analyses were additionally stratified on calendar periods: 2012–2014, 2015–2017 and 2018–2019.
Results
About 254 individuals, LTFU and 5547 DAA‐treated were included. Being institutionalized (OR = 5.02, 95% confidence interval (CI) = 3.29–7.65), household income below the social minimum (OR = 1.96, 95% CI = 1.25–3.06), receiving benefits (OR = 1.74, 95% CI = 1.20–2.52) and psychiatric comorbidity (OR = 1.51, 95% CI = 1.09–2.10) were associated with LTFU. Mortality rates were significantly higher in individuals LTFU compared to those DAA‐treated (2.99 vs. 1.15/100 person‐years (PY), p < .0001), while in those DAA‐treated, mortality rates slowly increased between 2012–2014 (.22/100PY) and 2018–2019 (2.25/100PY).
Conclusion
In the Netherlands, individuals who are incarcerated/institutionalized, with low household income, or with psychiatric comorbidities are prone to being LTFU, which is associated with higher mortality. HCV care needs to be adapted for these vulnerable individuals.
In the 2022 multicountry mpox (formerly named monkeypox) outbreak, several countries offered primary preventive vaccination (PPV) to people at higher risk for infection. We study vaccine acceptance ...and its determinants, to target and tailor public health (communication-) strategies in the context of limited vaccine supply in the Netherlands.
Online survey in a convenience sample of gay, bisexual and other men who have sex with men, including transgender persons (22/07-05/09/2022, the Netherlands). We assessed determinants for being (un)willing to accept vaccination. We used multivariable multinominal regression and logistic regression analyses, calculating adjusted odds ratios (aOR) and 95 percent confidence-intervals. An open question asked for campaigning and procedural recommendations.
Of respondents, 81.5% (
= 1,512/1,856) were willing to accept vaccination; this was 85.2% (799/938) in vaccination-eligible people and 77.7% (713/918) in those non-eligible. Determinants for non-acceptance included: urbanization (rural: aOR:2.2;1.2-3.7; low-urban: aOR:2.4;1.4-3.9; vs. high-urban), not knowing mpox-vaccinated persons (aOR:2.4;1.6-3.4), and lack of connection to gay/queer-community (aOR:2.0;1.5-2.7). Beliefs associated with acceptance were: perception of higher risk/severity of mpox, higher protection motivation, positive outcome expectations post vaccination, and perceived positive social norms regarding vaccination. Respondents recommended better accessible communication, delivered regularly and stigma-free, with facts on mpox, vaccination and procedures, and other preventive options. Also, they recommended, "vaccine provision also at non-clinic settings, discrete/anonymous options, self-registration" to be vaccinated and other inclusive vaccine-offers (e.g., also accessible to people not in existing patient-registries).
In the public health response to the mpox outbreak, key is a broad and equitable access to information, and to low-threshold vaccination options for those at highest risk. Communication should be uniform and transparent and tailored to beliefs, and include other preventive options. Mpox vaccine willingness was high. Public health efforts may be strengthened in less urbanized areas and reach out to those who lack relevant (community) social network influences.
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