Vaccine decision making in New Zealand: a discrete choice experiment.

BACKGROUND: Vaccine hesitancy is a significant threat to global health. A key part of addressing hesitancy is to ensure that public health messaging prioritises information that is considered important to the public. This study aimed to examine how different vaccine characteristics affect public preferences for vaccines in New Zealand, what trade-offs they are willing to make between different vaccine characteristics, and how their preferences are affected by their vaccine-related conspiracy beliefs and COVID-19 vaccination status. METHODS: An online discrete choice experiment (DCE) was designed to elicit individual preferences about vaccines using the 1000minds platform. Members of the general population of New Zealand aged ≥ 18 years were invited to complete the DCE. Participants were asked to indicate their preference between two options showing different combinations of vaccine characteristics. Data on sociodemographic characteristics were collected. Beliefs were measured using the vaccine conspiracy beliefs scale (VCBS) with scores ≥ 19 indicating strong vaccine-related conspiracy beliefs. The DCE was analysed using the PAPRIKA method (Potentially All Pairwise RanKings of all possible Alternatives) and preferences compared between respondents with high versus low VCBS scores and vaccinated versus unvaccinated respondents for COVID-19. RESULTS: A total of 611 respondents from 15 regions completed the DCE. Mean (SD) age was 45.9 (14.7) years with most having had 2 or more doses of the coronavirus vaccine (86%). Mean (SD) VCBS score was 18.5 (12.4) indicating moderate vaccine-related conspiracy beliefs. Risk of severe adverse effects was the most highly valued vaccine characteristic, followed by vaccine effectiveness and duration of protection. Vaccine origin and route of administration were ranked least important. Respondents scoring high on the VCBS placed less value on the effectiveness of vaccines but greater value on development time and total number of doses (p < 0.001). COVID-19 unvaccinated respondents ranked development time and total number of doses more highly than those vaccinated respondents (p < 0.001). CONCLUSIONS: Risk of severe adverse effects, vaccine effectiveness and duration of protection were rated by the New Zealand public as the top three most important vaccine characteristics. This information is important for informing public health messaging to promote vaccine uptake and inform vaccine decision-making.

Investigating rates and risk factors for hepatitis C virus reinfection in people receiving antiviral treatment in England.

England has committed to the World Health Organization target to eliminate hepatitis C virus (HCV) as a public threat by the year 2030. Given successful treatments for HCV in recent years, it is unclear whether HCV reinfection will impact England's ability to achieve HCV elimination. We aimed to estimate the HCV reinfection rate among a cohort of patients receiving antiviral treatment using available surveillance data. Linkage between a treatment dataset from 2015 to 2019 and an HCV RNA testing dataset were used to identify people who experienced reinfection using three criteria. A Cox proportional hazards model was used to determine risk factors associated with HCV reinfection among a cohort who received treatment and had follow-up HCV RNA testing. The reinfection rate among those receiving HCV treatment was 7.91 per 100 person-years (PYs, 95% confidence interval (CI) 7.37-8.49) and highest among current injecting drug users (22.55 per 100 PYs, 95% CI 19.98-25.46) and people who had been in prison (20.42 per 100 PYs, 95% CI 17.21-24.24). In the adjusted model, women had a significantly reduced risk of reinfection. Being of younger age, current injecting drug users, and receipt of first treatment in prison were each significantly associated with increased risk of reinfection. Two-fifths of those with reinfection (43%, n = 329/767) were linked to treatment after reinfection, and of those starting treatment, three quarters (75%, n = 222/296) achieved a sustained virologic response. Guidance for testing groups at risk of reinfection and harm reduction strategies to minimize transmission should be implemented if England is to achieve HCV elimination targets.

Changing Mindsets About Side Effects of the COVID-19 Vaccination: A Randomized Controlled Trial.

BACKGROUND: Side-effect concerns are a major barrier to vaccination against COVID-19 and other diseases. Identifying cost- and time-efficient interventions to improve vaccine experience and reduce vaccine hesitancy-without withholding information about side effects-is critical. PURPOSE: Determine whether a brief symptom as positive signals mindset intervention can improve vaccine experience and reduce vaccine hesitancy after the COVID-19 vaccination. METHODS: English-speaking adults (18+) were recruited during the 15-min wait period after receiving their second dose of the Pfizer COVID-19 vaccination and were randomly allocated to the symptom as positive signals mindset condition or the treatment as usual control. Participants in the mindset intervention viewed a 3:43-min video explaining how the body responds to vaccinations and how common side effects such as fatigue, sore arm, and fever are signs that the vaccination is helping the body boost immunity. The control group received standard vaccination center information. RESULTS: Mindset participants (N = 260) versus controls (N = 268) reported significantly less worry about symptoms at day 3 [t(506)=2.60, p=.01, d=0.23], fewer symptoms immediately following the vaccine [t(484)=2.75, p=.006, d=0.24], and increased intentions to vaccinate against viruses like COVID-19 in the future [t(514)=-2.57, p=.01, d=0.22]. No significant differences for side-effect frequency at day 3, coping, or impact. CONCLUSIONS: This study supports the use of a brief video aimed at reframing symptoms as positive signals to reduce worry and increase future vaccine intentions. CLINICAL TRIAL INFORMATION: Australian New Zealand Clinical Trials Registry: ACTRN12621000722897p.

Side-effect concerns are a major barrier to vaccination against COVID-19 and other diseases. Therefore, the purpose of this study was to determine whether a brief symptom as positive signals mindset intervention could improve vaccine experience and reduce vaccine hesitancy after the COVID-19 vaccination. Participants were recruited during the 15-min wait period after receiving their second dose of the Pfizer COVID-19 vaccination and were randomly allocated to a treatment as usual control condition or to a mindset intervention condition which entailed watching a 3:43-min video explaining how the body responds to vaccinations and how common side effects such as fatigue, sore arm, and fever are signs that the vaccination is helping the body boost immunity. Compared with participants in the control condition, participants in the mindset intervention condition reported significantly less worry about symptoms at day 3, fewer symptoms immediately following the vaccine and increased intentions to vaccinate against viruses like COVID-19 in the future. No significant differences emerged for side-effect frequency at day 3, coping, or impact. These finding provide initial support for cost- and time-efficient interventions to improve vaccine experience and reduce vaccine hesitancy without withholding information about side effects.

Core Outcome Set for Reporting Outcomes of Interventions for Velopharyngeal Dysfunction: Final Results of the COS-VPD Initiative.

OBJECTIVE: To date, the recording of outcomes of interventions for velopharyngeal dysfunction (VPD) has not been standardized. This makes a comparison of results between studies challenging. The aim of this study was to develop a core outcome set (COS) for reporting outcomes in studies examining the management of VPD. DESIGN: A two-round Delphi consensus process was used to develop the COS. PATIENTS, PARTICIPANTS: The expert Delphi panel comprised patients and caregivers of patients with VPD, surgeons and speech and language therapists specializing in cleft palate, and researchers with expertise in VPD. INTERVENTIONS: A long list of outcomes was derived from the published literature. In each round of a Delphi survey, participants were asked to score outcomes using the Grading of Recommendations, Assessment, Development, and Evaluations scale of 1 to 9, with 1 to 3 labeled "not important," 4 to 6 labeled "important but not critical," and 7 to 9 labeled "critical." MAIN OUTCOME MEASURE: Consensus criteria were specified a priori. Outcomes with a rating of 75% or more of the panel rating 7 to 9 and 25% or fewer rating 1 to 3 were included in the COS. RESULTS: A total of 31 core outcomes were identified from the Delphi process. This list was condensed to combine topic areas to produce a final COS of 10 outcomes, including both processes of care and patient-reported outcomes that should be considered for reporting in future studies of VPD. CONCLUSIONS: Implementation of the COS-VPD will facilitate consistency of outcomes data collection and comparison of results across studies.

A retrospective comparison of respiratory events with JAK inhibitors or rituximab for rheumatoid arthritis in patients with pulmonary disease.

Janus kinase inhibitors (JAKi) are an exciting option for the treatment of rheumatoid arthritis (RA) but little is known about their safety and tolerability in patients with existing respiratory disorders. The objective was to compare pulmonary safety of JAKi versus rituximab in patients with concurrent interstitial lung disease (ILD) or bronchiectasis. We performed a retrospective electronic patient record review of patients with known ILD or bronchiectasis commencing JAKi or rituximab for the treatment of RA. Patients initiating treatment from January 2016 to February 2020 were included. Respiratory events (hospitalization or death from a respiratory cause) were compared using Kaplan-Meier survival analysis. We analysed patients who received JAKi (n = 28) and rituximab (n = 19) for a mean (SD) of 1.1 (0.62) and 2.14 (1) years respectively. Patients were predominantly female (68%), anti-CCP antibody positive (94%) and non-smoking (89%) with a median (IQR) percentage predicted FVC at baseline of 100% (82-115%) and percentage predicted TLCO of 62% (54.5-68%). Respiratory events occurred in five patients treated with JAKi (18%; 5 hospitalizations, 2 deaths) and in four patients treated with rituximab (21%; 3 hospitalizations, 1 death). Respiratory event rates did not differ between groups (Cox-regression proportional hazard ratio = 1.38, 95% CI 0.36-5.28; p = 0.64). In this retrospective study, JAKi for the treatment of RA with existing ILD or bronchiectasis did not increase the rate of hospitalization or death due to respiratory causes compared to those treated with rituximab. JAK inhibition may provide a relatively safe option for RA in such patients.

Pneumococcal Conjugate Vaccines Turning the Tide on Inequity: A Retrospective Cohort Study of New Zealand Children Born 2006-2015.

BACKGROUND: Hospitalization rates for infectious diseases in New Zealand (NZ) children have increased since 1989. The highest burden is among Maori and Pacific children, and the most socioeconomically deprived. New Zealand introduced pneumococcal conjugate vaccine (PCV)7 in June 2008, PCV10 in 2011, and PCV13 in 2014. METHODS: A retrospective cohort study of NZ children aged <6 years between 2006 and 2015 was performed using administrative databases. Demographics and hospitalizations were linked to evaluate the impact of the PCV vaccination program on cases of invasive pneumococcal disease (IPD), all-cause pneumonia (ACP), and otitis media (OM), defined by ICD-10-AM codes, and to explore the effect by ethnicity and deprivation. RESULTS: Between 2006 and 2015, there were 640 children hospitalized with IPD, 26589 for ACP, and 44545 for OM. IPD hospitalizations declined by 73% between 2005 and 2015 for children <6 years of age, whereas ACP and OM declined by 8% and 25%, respectively. The highest rates for all diseases were among Maori and Pacific children and those from high deprivation. However, the declines were highest among Maori and Pacific children and those from socioeconomically deprived areas. IPD hospitalizations declined by 79% and 67% for Maori and Pacific children, respectively, between 2006 and 2015. ACP declined by 12% in Maori and 21% in Pacific children. OM declined by 51% in Maori children. CONCLUSION: In contrast to the increasing trend of hospitalization rates for infectious disease in New Zealand, the use of PCV appears associated with reductions in ethnic and socioeconomic disparities in hospitalization for IPD, ACP, and OM.

Monitoring the hepatitis C epidemic in England and evaluating intervention scale-up using routinely collected data.

In England, 160 000 individuals were estimated to be chronically infected with hepatitis C virus (HCV) in 2005 and the burden of severe HCV-related liver disease has increased steadily for the past 15 years. Direct-acting antiviral treatments can clear infection in most patients, motivating HCV elimination targets. However, the current burden of HCV is unknown and new methods are required to monitor progress. We employed a Bayesian back-calculation approach, combining data on severe HCV-related liver disease and disease progression, to reconstruct historical HCV incidence and estimate current prevalence in England. We explicitly modelled infections occurring in people who inject drugs, the key risk group, allowing information on the size of this population and surveillance data on HCV prevalence to inform recent incidence. We estimated that there were 143 000 chronic infections in 2015 (95% credible interval 123 000-161 000), with 34% and 54% in those with recent and past injecting drug use, respectively. Following the planned scale-up of new treatments, chronic infections were predicted to fall to 113 400 (94 900-132 400) by the end of 2018 and to 89 500 (71 300-108 600) by the end of 2020. Numbers developing severe HCV-related liver disease were predicted to fall by at least 24% from 2015 to 2020. Thus, we describe a coherent framework to monitor progress using routinely collected data, which can be extended to incorporate additional data sources. Planned treatment scale-up is likely to achieve 2020 WHO targets for HCV morbidity, but substantial efforts will be required to ensure that HCV testing and patient engagement are sufficiently high.

Comparison of vaccination coverage of four childhood vaccines in New Zealand and New York State.

AIM: To ensure that children are vaccinated, different national governments use diverse strategies. We compared childhood vaccination coverage rates between New York State (NYS) and New Zealand (NZ) as the vaccination strategies are different. METHODS: We used vaccination records from the NYS Immunisation Information System and the National Immunisation Register of NZ to measure (i) vaccination coverage by school entry and by age six; (ii) coverage of different socio-demographic groups; and (iii) trend in vaccination coverage between 2011 and 2015. RESULTS: We analysed the records of 583 767 NYS children and 269 800 NZ children 7 years of age. NZ children were 3.3-21.5% more likely than NYS children to receive each of the vaccines. Compared to NYS, NZ children were 39.6% more likely to be up-to-date by the start of school and 28.1% more likely to be up-to-date by age 6 years. Both NYS and NZ had statistically significant increases in the proportion of children who were up to date on each vaccine and all vaccines by the start of school and by 6 years of age (P < 0.001). CONCLUSIONS: We identified under-vaccinated groups and examined the point in the vaccine series where children were most vulnerable to being under-vaccinated. This information is useful in targeting future investigations and interventions aimed at mitigating disparities in vaccine coverage. This comparison of regions with different vaccination programmes and policies is important when considering whether the particular vaccination coverage strategies of one region could be adapted and applied for the benefit of another.

Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: a retrospective case-control study.

BACKGROUND: Gonorrhoea is a major global public health problem that is exacerbated by drug resistance. Effective vaccine development has been unsuccessful, but surveillance data suggest that outer membrane vesicle meningococcal group B vaccines affect the incidence of gonorrhoea. We assessed vaccine effectiveness of the outer membrane vesicle meningococcal B vaccine (MeNZB) against gonorrhoea in young adults aged 15-30 years in New Zealand. METHODS: We did a retrospective case-control study of patients at sexual health clinics aged 15-30 years who were born between Jan 1, 1984, and Dec 31, 1998, eligible to receive MeNZB, and diagnosed with gonorrhoea or chlamydia, or both. Demographic data, sexual health clinic data, and National Immunisation Register data were linked via patients' unique personal identifier. For primary analysis, cases were confirmed by laboratory isolation or detection of Neisseria gonorrhoeae only from a clinical specimen, and controls were individuals with a positive chlamydia test only. We estimated odds ratios (ORs) comparing disease outcomes in vaccinated versus unvaccinated participants via multivariable logistic regression. Vaccine effectiveness was calculated as 100×(1-OR). FINDINGS: 11 of 24 clinics nationally provided records. There were 14 730 cases and controls for analyses: 1241 incidences of gonorrhoea, 12 487 incidences of chlamydia, and 1002 incidences of co-infection. Vaccinated individuals were significantly less likely to be cases than controls (511 [41%] vs 6424 [51%]; adjusted OR 0·69 [95% CI 0·61-0·79]; p<0·0001). Estimate vaccine effectiveness of MeNZB against gonorrhoea after adjustment for ethnicity, deprivation, geographical area, and sex was 31% (95% CI 21-39). INTERPRETATION: Exposure to MeNZB was associated with reduced rates of gonorrhoea diagnosis, the first time a vaccine has shown any protection against gonorrhoea. These results provide a proof of principle that can inform prospective vaccine development not only for gonorrhoea but also for meningococcal vaccines. FUNDING: GSK Vaccines.

Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation.

The tetraspanins are a superfamily of four-transmembrane proteins, which regulate the trafficking, lateral diffusion and clustering of the transmembrane proteins with which they interact. We have previously shown that tetraspanin Tspan9 is expressed on platelets. Here we have characterised gene-trap mice lacking Tspan9. The mice were viable with normal platelet numbers and size. Tspan9-deficient platelets were specifically defective in aggregation and secretion induced by the platelet collagen receptor GPVI, despite normal surface GPVI expression levels. A GPVI activation defect was suggested by partially impaired GPVI-induced protein tyrosine phosphorylation. In mechanistic experiments, Tspan9 and GPVI co-immunoprecipitated and co-localised, but super-resolution imaging revealed no defects in collagen-induced GPVI clustering on Tspan9-deficient platelets. However, single particle tracking using total internal reflection fluorescence microscopy showed that GPVI lateral diffusion was reduced by approximately 50% in the absence of Tspan9. Therefore, Tspan9 plays a fine-tuning role in platelet activation by regulating GPVI membrane dynamics.

A large two-centre study in to rates of influenza and pneumococcal vaccination and infection burden in rheumatoid arthritis in the UK.

BACKGROUND: Infections are a common complication of RA with associated morbidity and mortality. The aetiology of increased risk is complex and multifactorial. Despite this, strategies to mitigate against risk of infection including vaccination are not always addressed in primary or secondary care with wide variation in practice from multiple small single centre audits. This study was a large two-centre survey of vaccine uptake in routine clinical practice and evaluated the relationship between vaccination and the burden of infection in RA patients. METHODS: A patient questionnaire was devised and disseminated through postal, clinic and phone survey at 2 UK rheumatology centres, detailing past vaccination history, reasons for non-vaccination, and history of recent infection. In a subset of patients, primary care vaccination data were also obtained. RESULTS: In total 929 patients responded to the survey. Over 85 % of patients were vaccinated against influenza, however only 44 % were vaccinated against pneumococcus. The vast majority of vaccination was undertaken in primary care. In the 12 months prior to the survey, 7.7 % of subjects recalled at least one episode of severe infection requiring admission, and nearly 40 % reported receiving at least one course of antibiotics. CONCLUSIONS: Infections are common in RA and Rheumatologists need to be adept at recognising at risk patients and managing them appropriately. Influenza vaccination uptake is good whilst pneumococcal vaccination rates are comparatively poor. Collaborative approaches between primary and secondary care are required to maximise vaccine uptake, which is safe and recommended in RA patients.

Cognition in Adult Bereavement: Preliminary Findings From Five Hospice Bereavement Focus Groups.

Grief is an experience of both common and unique responses (Hooyman & Kramer, 2006). Grief affects people in various ways including emotionally, cognitively, socially, physically, and spiritually (Corr, 2007; Doka, 2014). Little has been published on the cognitive domain of loss affecting attention, and concentration of bereaved adults. This qualitative study explored these effects among adults in one hospice bereavement program in Central Texas. Five focus groups included facilitated bereavement topical conversations resulting in descriptions of memory, concentration, and attention deficits after loss. These results suggested that participation in bereavement programming may normalize the experience facilitating cognitive task accomplishment. Referrals for bereavement care may be appropriate in order to facilitate equilibrium in individual's lives following a significant death.

Increased uptake and new therapies are needed to avert rising hepatitis C-related end stage liver disease in England: modelling the predicted impact of treatment under different scenarios.

BACKGROUND & AIMS: Hepatitis C (HCV) related disease in England is predicted to rise, and it is unclear whether treatment at current levels will be able to avert this. The aim of this study was to estimate the number of people with chronic HCV infection in England that are treated and assess the impact and costs of increasing treatment uptake. METHODS: Numbers treated were estimated using national data sources for pegylated interferon supplied, dispensed, or purchased from 2006 to 2011. A back-calculation approach was used to project disease burden over the next 30 years and determine outcomes under various scenarios of treatment uptake. RESULTS: 5000 patients were estimated to have been treated in 2011 and 28,000 in total from 2006 to 2011; approximately 3.1% and 17% respectively of estimated chronic infections. Without treatment, incident cases of decompensated cirrhosis and hepatocellular carcinoma were predicted to increase until 2035 and reach 2290 cases per year. Treatment at current levels should reduce incidence by 600 cases per year, with a peak around 2030. Large increases in treatment are needed to halt the rise; and with more effective treatment the best case scenario predicts incidence of around 500 cases in 2030, although treatment uptake must still be increased considerably to achieve this. CONCLUSIONS: If the infected population is left untreated, the number of patients with severe HCV-related disease will continue to increase and represent a substantial future burden on healthcare resources. This can be mitigated by increasing treatment uptake, which will have the greatest impact if implemented quickly.

Evidence for sodium metasilicate receptors on the human osteoblast cell surface; spatial localization and binding properties.

We report details of the interaction of sodium metasilicate with osteoblast cellular membranes using Fluoresceinphosphatidylethanolamine (FPE) as a fluorescent indicator of membrane interactions. Fluorescence imaging studies of the FPE-based indicator system revealed areas of localized binding that would be consistent with the presence of a structure with 'receptor-like' properties. From these results, it seems unlikely that silica binds 'non-specifically' to the osteoblast surface. Moreover, the receptors are localized into membrane domains. Such regions of the cell membrane could well be structures such as 'rafts' or other such localized domains within the membrane. The binding profile of silica with the osteoblast cell surface takes place with all the characteristics of a receptor-mediated process best represented by a cooperativity (sigmoidal) binding model with a Hill coefficient of 3.6.

Pertussis epidemiology in adults: Retrospective analysis of pertussis incidence and association with comorbidities among adult populations in Aotearoa New Zealand, using national administrative datasets.

BACKGROUND: In New Zealand, approximately half reported pertussis cases are adult. Studies indicate underestimated pertussis burden in this population and probable reservoir for childhood pertussis. Pertussis is linked to chronic obstructive pulmonary disease (COPD) development and increased risk with pre-existing COPD. While acellular pertussis vaccines are available for adults, data on pertussis disease burden in adults and association with COPD remain limited. AIM: To estimate pertussis incidence in New Zealand adult health service user (HSU) population aged ≥ 18 between 2008-2019 and inform adult pertussis vaccination strategies by assessing disease burden and risk factors in different adult populations. METHODS: Retrospective observational cohort study using an HSU cohort, formed by linking administrative health data using unique National Health Index identifier. For primary analysis, annual incidence rates were calculated using pertussis hospitalisations and notifications. In secondary analysis, Cox proportional hazards survival analyses explored association between pertussis in adults and chronic comorbidities. RESULTS: The cohort had 2,907,258 participants in 2008 and grew to 3,513,327 by 2019, with 11,139 pertussis cases reported. Highest annual incidence rate of 84.77 per 100,000 PYRS in 2012, notably affecting females, those aged 30-49 years, and European or Maori ethnicity. Adjusting for sociodemographic variables found no significant risk of prior pertussis notification leading to comorbidity diagnosis (Adjusted-HR: 0.972). However, individuals with prior comorbidity diagnosis had 16 % greater risk of receiving pertussis notification or diagnosis (Adjusted-HR: 1.162). CONCLUSIONS: Study found significant pertussis burden among the HSU adult cohort and highlighted higher risk of pertussis for those with recent comorbidity diagnoses. Vaccination for pertussis should be recommended for individuals with comorbidities to reduce infection risk and disease severity. GPs must have capability to test for pertussis, given it is notifiable disease with implications for individuals, their families, and broader population. High-quality disease surveillance is crucial for informing policy decisions.

Early infection events highlight the limited transmissibility of hepatitis C virus in vitro.

BACKGROUND & AIMS: Hepatitis C virus (HCV) poses a global health problem, with over 170 million chronically infected individuals at risk of developing progressive liver disease. The ability of a virus to spread within a host is a key determinant of its persistence and virulence. HCV can transmit in vitro by cell-free particle diffusion or via contact(s) between infected and naïve hepatocytes. However, limited information is available on the relative efficiency of these routes, our aim is to develop physiologically relevant assays to quantify these processes. METHODS: We developed a single-cycle infection assay to measure HCV transmission rates. RESULTS: We compared HCV spread in proliferating and arrested cell systems and demonstrated a significant reduction in cell-to-cell infection of arrested target cells. Comparison of cell-free and cell-to-cell virus spread demonstrated relatively poor transmission rates, with 10-50 infected producer cells required to infect a single naïve target cell. We found HCV strain J6/JFH to be 10-fold more efficient at spreading via the cell-to-cell route than cell-free, whereas SA13/JFH and HK6/JFH strains showed comparable rates of infection via both routes. Importantly, the level of infectious virus released from cells did not predict the ability of a virus to spread in vitro, highlighting the importance of studying cell-associated viruses. CONCLUSIONS: These studies demonstrate the relatively poor infectivity of HCV and highlight differences between strains in their efficiency and preferred route of transmission that may inform future therapeutic strategies that target virus entry.

Hepatitis C virus induces CD81 and claudin-1 endocytosis.

Hepatitis C virus (HCV) leads to progressive liver disease and hepatocellular carcinoma. Current treatments are only partially effective, and new therapies targeting viral and host pathways are required. Virus entry into a host cell provides a conserved target for therapeutic intervention. Tetraspanin CD81, scavenger receptor class B member I, and the tight-junction proteins claudin-1 and occludin have been identified as essential entry receptors. Limited information is available on the role of receptor trafficking in HCV entry. We demonstrate here that anti-CD81 antibodies inhibit HCV infection at late times after virus internalization, suggesting a role for intracellular CD81 in HCV infection. Several tetraspanins have been reported to internalize via motifs in their C-terminal cytoplasmic domains; however, CD81 lacks such motifs, leading several laboratories to suggest a limited role for CD81 endocytosis in HCV entry. We demonstrate CD81 internalization via a clathrin- and dynamin-dependent process, independent of its cytoplasmic domain, suggesting a role for associated partner proteins in regulating CD81 trafficking. Live cell imaging demonstrates CD81 and claudin-1 coendocytosis and fusion with Rab5 expressing endosomes, supporting a role for this receptor complex in HCV internalization. Receptor-specific antibodies and HCV particles increase CD81 and claudin-1 endocytosis, supporting a model wherein HCV stimulates receptor trafficking to promote particle internalization.