Candidate vaccine efficacies (60%, 70% and 80%) were educated by preceding HCV vaccine modelling [32] and consultation with investigators involved in a current Phase I/II HCV preventive vaccine trial among PWID in the US (ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT01436357″,”term_id”:”NCT01436357″NCT01436357). Sample size projections for the estimates of chronic HCV infection stratified by candidate efficacy were calculated (Tables 5 and ?and6).6). least 12/100 py (primary HCV infection rate 16/100 py) will be required for stand-alone trials of highly efficacious candidates designed to prevent chronic infection. However, elevated primary HCV infection was observed among participants not receiving opioid substitution therapy who reported heroin as the main drug injected (26.9/100 py 95% CI 14.5, 50.0) and those who reported unstable housing (23.5/100 py 95% CI 7.6, 72.8), daily or more frequent injecting (22.7/100 py 95% CI 12.2, 42.2) and receptive syringe sharing (23.6/100 py 95% CI 9.8, 56.7) in the six months prior to baseline. These data suggest that SSE15206 it is possible to recruit and retain at-risk PWID who adhere to study protocols and that modification of eligibility criteria may identify populations with sufficiently high HCV incidence. Results support the feasibility of large multi-centre HCV vaccine trials, including in the Australian setting. strong class=”kwd-title” Keywords: hepatitis C virus, vaccine preparedness study, people who inject drugs Introduction Feasibility or vaccine preparedness studies (VPS) support Phase III vaccine trial design through increasing understanding of the mechanisms and effects of interventions, identifying barriers to trial participation, improving ethical informed consent procedures, and informing recruitment, retention and adherence strategies [1C3]. VPS lay the groundwork for future trials by answering key scientific questions, building community capacity, and establishing the necessary infrastructure for trial conduct [2]. A key aim of these studies is to demonstrate capacity to recruit and retain at-risk individuals with sufficient clinical trial literacy (CTL) and willingness to participate (WTP) in future trials [1, 4]. Identified over 20 years ago [5], the hepatitis C virus (HCV) is a major cause of morbidity and mortality worldwide with approximately 3% of the worlds population infected [6]. Chimpanzee studies indicate that generation of protective immunity against HCV via vaccination is possible [7C10]. In two Phase I trials, preventive vaccines candidates were shown to be safe and immunogenic [11, 12]. An additional two trials in humans are currently in progress. The first is a Phase I trial of healthy volunteers and people with HCV (ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT01296451″,”term_id”:”NCT01296451″NCT01296451) and the second is a staged Phase I/II trial of the same preventive candidate among people who inject drugs (PWID)(ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT01436357″,”term_id”:”NCT01436357″NCT01436357). As the key population at risk of HCV in developed countries [13], effective engagement and recruitment of large numbers of exposed but uninfected PWID will be required for successful Phase III vaccine trials. Trials of candidate HCV vaccines are likely to face particular challenges in attracting and retaining suitable participants and in developing appropriate protocols to assess safety, immunogenicity and efficacy [1]. The identification of populations with sufficiently high HCV incidence to demonstrate vaccine candidate efficacy will be of particular importance. Previous Australian studies have documented high incidence of HCV among PWID [14, 15]. HCV incidence in community-based cohorts of PWID has ranged between 10.7/100 py (95% CI 6.8, 16.8) [1990C1995] in Victoria [16], 30.8/100 py Rat monoclonal to CD4.The 4AM15 monoclonal reacts with the mouse CD4 molecule, a 55 kDa cell surface receptor. It is a member of the lg superfamily,primarily expressed on most thymocytes, a subset of T cells, and weakly on macrophages and dendritic cells. It acts as a coreceptor with the TCR during T cell activation and thymic differentiation by binding MHC classII and associating with the protein tyrosine kinase, lck (95% CI 24.3, 39.0) [1999C2002] in NSW and 44.1/100 py (95% CI 34.4C56.6) [1999C2002] in South West Sydney [17]. However, recent evidence suggests that HCV incidence may be declining among Australian PWID [18]. Temporal variations in HCV incidence highlight the importance of current and accurate estimates of HCV incidence, which are crucial to power trials of candidates designed to prevent chronic HCV infection. Of note, the preventive vaccine candidate currently being assessed (ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT01436357″,”term_id”:”NCT01436357″NCT01436357 & “type”:”clinical-trial”,”attrs”:”text”:”NCT01296451″,”term_id”:”NCT01296451″NCT01296451) aims to elicit a T-cell response associated with spontaneous clearance SSE15206 and therefore viral persistence estimates (progression to chronic HCV infection) are necessary for sample size projections for Phase III assessment. While HIV VPS have included PWID, this population has typically comprised only a minority of study participants [19C21]. As part of the first HCV SSE15206 VPS, this paper reports key outcomes impacting HCV vaccine trial feasibility in PWID based on a community-based prospective observational study of HCV antibody negative PWID C the Hepatitis C Incidence and Transmission Study- community (HITS-c). The study aimed to identify 1) retention at 48 weeks; 2) adherence to study protocols; 3) HCV incidence by baseline characteristics and risk behaviour; 4) progression to chronic HCV infection; and SSE15206 5) sample size estimates for future trials based on retention and chronic HCV infection observed in the HITS-c cohort..