Low Hepatitis C Virus Prevalence among Men Who Have Sex with Men Attending Public Health Services in The Netherlands

The hepatitis C virus (HCV) prevalence is high among men who have sex with men (MSM) with HIV in the Netherlands. Large reductions in HCV incidence among MSM with HIV, however, have occurred since treatment with direct-acting antivirals. Over the years, a broader understanding of the HCV epidemic has shown that HCV infections are not solely restricted to MSM with HIV, but they also occur among HIV-negative MSM. Currently, HCV testing among HIV-negative MSM is only provided for PrEP users and is not part of routine sexually transmitted infection (STI) screening among HIV-negative MSM who are not using PrEP. In this study, we screened 1885 HIV-negative MSM who did not participate in a PrEP program, with over 1966 STI screening visits at four different public health clinic sites. Among the 1885 MSM, only one person had a new HCV infection, resulting in a 0.05% (95% confidence interval 0.0–0.3) incidence. Based on our findings, we can conclude that systematic HCV testing at STI clinics may not yield significant benefits for this particular population.</p

Targeted HCV core antigen monitoring among HIV-positive men who have sex with men is cost-saving

Introduction: The World Health Organization declared the goal of hepatitis Cvirus (HCV) elimination by 2030. Micro-elimination, which is the reduction of incidence to zero in targeted populations, is less complex and costly and may be the first step to prove whether elimination is feasible. Asuitable target group are HIV-positive men who have sex with men (MSM) because of their high-risk behaviour and high incidence rates. Moreover, HCV monitoring is integrated in HIV care. The current HCV monitoring approach is suboptimal and complex and may miss new HCV infections. Alternative monitoring strategies, based on alanine aminotransferase, HCV-PCRand HCV-core antigen (HCV-cAg), combined with immediate direct-acting antiviral (DAA) treatment, may be more effective in reducing new HCV infections. Methods: Adeterministic mathematical transmission model was constructed representing the Dutch HCV epidemic among HIV-positive MSM to compare different HCV monitoring strategies from 2018 onwards. We evaluated the epidemiological impact of alternative and intensified monitoring in MSM with HCV. In addition, the cost-effectiveness was calculated over a lifetime horizon. Results: Current HCV monitoring and treatment is projected to result in an incidence of 1.1/1000 person-years, 0.24% prevalence, at a cost of 61.8 million (interquartile range 52.2-73.9). Compared with current monitoring, intensified monitoring will result in a maximum 27% reduction of incidence and 33% in prevalence at an increased cost. Conversely, compared with current monitoring, targeted HCV-cAg monitoring will result in a comparable incidence (1.1/1000 person-years) and prevalence (0.23%) but will be 1 million cheaper with increased quality-adjusted life year. Conclusion: Targeted monitoring reduces the HCV epidemic in a cost-saving manner; however, micro-elimination may not be obtained by 2030, highlighting the need for harm-reduction programmes

Health Outcomes and Cost-effectiveness of Monoclonal SARS-CoV-2 Antibodies as Pre-exposure Prophylaxis

Importance: Pre-exposure prophylaxis with neutralizing SARS-CoV-2 monoclonal antibodies (mAbs PrEP) prevents infection and reduces hospitalizations and the duration thereof for COVID-19 and death among high-risk individuals. However, reduced effectiveness due to a changing SARS-CoV-2 viral landscape and high drug prices remain substantial implementation barriers. Objective: To assess the cost-effectiveness of mAbs PrEP as COVID-19 PrEP. Design, Setting, and Participants: For this economic evaluation, a decision analytic model was developed and parameterized with health care outcome and utilization data from individuals with high risk for COVID-19. The SARS-CoV-2 infection probability, mAbs PrEP effectiveness, and drug pricing were varied. All costs were collected from a third-party payer perspective. Data were analyzed from September 2021 to December 2022. Main Outcomes and Measures: Health care outcomes including new SARS-CoV-2 infections, hospitalization, and deaths. The cost per death averted and cost-effectiveness ratios using a threshold for prevention interventions of $22000 or less per quality-adjusted life year (QALY) gained. Results: The clinical cohort consisted of 636 individuals with COVID-19 (mean [SD] age 63 [18] years; 341 [54$275 and 75% or higher effectiveness. With a 100% effectiveness mAbs PrEP can reduce ward admissions by 70%, ICU admissions by 97%, and deaths by 92%. Drug prices, however, need to reduce to $550 for cost-effectiveness ratios less than$22000 per QALY gained per death averted and to $2200 for ratios between$22000 and $88000. Conclusions and Relevance: In this study, use of mAbs PrEP for preventing SARS-CoV-2 infections was cost-saving at the beginning of an epidemic wave (high infection probability) with 75$275. These results are timely and relevant for decision-makers involved in mAbs PrEP implementation. When newer mAbs PrEP combinations become available, guidance on implementation should be formulated ensuring a fast rollout. Nevertheless, advocacy for mAbs PrEP use and critical discussion on drug prices are necessary to ensuring cost-effectiveness for different epidemic settings.</p

The global campaign to eliminate HBV and HCV infection: International Viral Hepatitis Elimination Meeting and core indicators for development towards the 2030 elimination goals

Hepatitis B virus (HBV) and hepatitis C virus (HCV) affect more than 320 million people worldwide, which is more than HIV, tuberculosis (TB) and malaria combined. Elimination of HBV and HCV will, therefore, produce substantial public health and economic benefits and, most importantly, the prevention of 1.2 million deaths per year. In 2016, member states of the World Health Assembly unanimously adopted a resolution declaring that viral hepatitis should be eliminated by 2030. Currently, few countries have elimination programmes in place and even though the tools to achieve elimination are available, the right resources, commitments and allocations are lacking. During the fifth International Viral Hepatitis Elimination Meeting (IVHEM), 7–8 December 2018, Amsterdam, the Netherlands, an expert panel of clinicians, virologists and public health specialists discussed the current status of viral hepatitis elimination programmes across multiple countries, challenges in achieving elimination and the core indicators for monitoring progress, approaches that have failed and successful elimination plans

Emergence and Persistence of Letermovir-Resistant Cytomegalovirus in a Patient with Primary Immunodeficiency

Background: Letermovir is a novel cytomegalovirus antiviral that is approved for prophylaxis in hematopoietic stem cell transplantation recipients Methods: After obtaining informed consent, letermovir prophylaxis was started in a patient with a presumed late-onset primary, combined T-and B-cell immunodeficiency. Plasma CMV DNAemia was monitored with real-time polymerase chain reaction, and letermovir resistance analyses were performed using Sanger sequencing and Illumina MiSeq next-generation sequencing. Results: A letermovir-resistant cytomegalovirus variant (C325Y mutation in UL56) emerged 17 weeks after start of prophylaxis. The letermovir-resistant variant was able to reactivate without drug selective pressure as this variant was again detected in plasma 20.6 weeks after stopping of letermovir. Conclusions: This case indicates that the C325Y mutation in UL56 does not significantly alter fitness of cytomegalovirus in vivo

The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures

Background: Approximately 71 million people are still in need of direct-acting antiviral agents (DAAs). To achieve the World Health Organization Hepatitis C elimination goals, insight into the prevalence and influence of resistance associated substitutions (RAS) is of importance. Collaboration is key since DAA failure is rare and real-life data are scattered. We have established a European collaboration, HepCare, to perform in-depth analysis regarding RAS prevalence, patterns, and multiclass occurrence. Methods: Data were extracted from the HepCare cohort of patients who previously failed DAA therapy. Geno-and subtypes were provided by submitters and mostly based on in-house assays. They were reassessed using the Comet HCV subtyping tool. We considered RAS to be relevant if they were associated with DAA failure in vivo previously reported in literature. Results: We analyzed 938 patients who failed DAA therapy from ten different European countries. There were 239 genotypes (GT) 1a, 380 GT1b, 19 GT2c, 205 GT3a, 14 GT4a, and 68 GT4d infections. Several unusual subtypes (n = 15) (GT1b/g/l, GT3b, GT4k/n/r/t) were present. RAS appeared in over 80% of failures and over a quarter had three or more RAS. Multiclass RAS varied over target region and genotype between 0-48%. RAS patterns such as the Q30R + L31M and Q30R + Y93H in GT1a, the L31V + Y93H and L31V + Y93H for GT1b, and A30K + L31M and A30K/V + Y93H for GT3a all occurred with a prevalence below 5%. Conclusion: RAS occur frequently after DAA failures and follow a specific genotype and drug related pattern. Interpretation of the influence of RAS on retreatment is challenging due to various patterns, patients' characteristics, and previous treatment history. Moving towards HCV elimination, an ongoing resistance surveillance is essential to track the presence of RAS, RAS patterns and gather data for a re-treatment algorithm

Transmission of NS5A-Inhibitor Resistance-Associated Substitutions among Men Who Have Sex with Men Recently Infected with Hepatitis C Virus Genotype 1a

The transmission of direct-acting antiviral resistance-associated substitutions (RAS) could hamper hepatitis C virus (HCV) cure rates and elimination efforts. A phylogenetic analysis of 87 men who have sex with men recently infected with HCV genotype 1a placed one-third (28/87) in a large cluster, in which 96% harbored NS5A M28V RAS.</p

Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus-Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy

Background Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)–positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recru