Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia.

Background: Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported. Methods: We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome. Results: Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir. Conclusions: In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.

Setting foot in private spaces: extending the hepatitis C cascade of care to automatic needle/syringe dispensing machines, a mixed methods study.

BACKGROUND: Global commitment to achieving hepatitis C virus (HCV) elimination has enhanced efforts in improving access to direct-acting antiviral (DAA) treatments for people who inject drugs (PWID). Scale-up of efforts to engage hard-to-reach groups of PWID in HCV testing and treatment is crucial to success. Automatic needle/syringe dispensing machines (ADMs) have been used internationally to distribute sterile injecting equipment. ADMs are a unique harm reduction service, affording maximum anonymity to service users. This paper explores the feasibility and acceptability of extending the HCV cascade of care to sites where ADMs are located. METHODS: The ADM users into Treatment (ADMiT) study was undertaken in a metropolitan region in Sydney, Australia. This mixed methods study involved analysis of closed-circuit television footage, ethnographic methods (fieldwork observation and in-depth interviews) and structured surveys. Researchers and peers conducted fieldwork and data collection over 10 weeks at one ADM site, including offering access to HCV testing and treatment. RESULTS: Findings from 10 weeks of fieldwork observations, 70 survey participants and 15 interviews highlighted that there is scope for engaging with this population at the time they use the ADM, and enhanced linkage to HCV testing and treatment may be warranted. Most survey participants reported prior HCV testing, 61% in the last 12 months and 38% had received HCV treatment. However, fieldwork revealed that most people observed using the ADM were not willing to engage with the researchers. Field work data and interviews suggested that extending the HCV cascade of care to ADMs may encroach on what is a private space for many PWID, utilized specifically to avoid engagement. DISCUSSION: Enhanced linkage to HCV testing and treatment for people who use ADMs may be warranted. However, data suggested that extending the HCV cascade of care to ADMs may encroach on what is a private space for many PWID, utilized specifically to avoid engagement. The current study raises important public health questions about the need to ensure interventions reflect the needs of affected communities, including their right to remain anonymous.

Acceptability of external jugular venepuncture for patients with liver disease and difficult venous access.

BACKGROUND: Difficult venous access (DVA) is common in liver patients requiring blood collection using traditional peripheral approaches. This study aimed to understand the experience of DVA for liver patients and the acceptability of peripheral venepuncture versus external jugular venepuncture (EJV). A secondary aim was to explore the impact of EJV on local resource utilization. METHODS: Semistructured interviews with liver outpatients with DVA (n = 10) requiring venepuncture were firstly themed inductively. We then deductively applied the acceptability framework of Sekhon et al. as a further analytic lens. Audit data from DVA encounters (n = 24) allowed analysis of issues from multiple perspectives. The Consolidated Criteria for Reporting Qualitative Research reporting checklist guides this report. RESULTS: Peripheral venepuncture had poor prospective, concurrent, and retrospective acceptability, requiring significant mental and physical preparation. Fear, stigma, pain and distress, poor continuity of care, and poor effectiveness led to service disengagement. While EJV caused initial trepidation, it had high concurrent and retrospective acceptability. The significant improvement in patient experience was corroborated by audit data for both procedure duration (5 versus 15 minutes) and first attempt success (100 versus 28.5%) for EJV versus peripheral venepuncture, respectively. While EJV required a recumbent position, it required less staff. CONCLUSIONS: EJV is highly acceptable to patients, using less time and staff resources. EJV protocols and staff training should be considered where DVA presentations are common. Individualized care plans and careful care coordination could divert DVA patients needing venepuncture to services that use EJV preferentially. HIGHLIGHTS Peripheral venepuncture results in fear, stigma, pain, & distress for those with DVA. This poor acceptability of traditional venepuncture leads to service disengagement. External jugular venepuncture is highly acceptable & improves resource utilization.

Improving access to HCV treatment: external jugular venepuncture can overcome problems with difficult venous access.

Many patients requiring antiviral treatment of chronic hepatitis C (HCV) have a background of significant injection drug use (IDU). In a proportion of patients, IDU results in difficulty with blood collection from conventional sites. We audited patients from the Liver Clinics and Drug Health Pharmacotherapy Service of The Royal Prince Alfred Hospital (RPAH) to determine the incidence of difficulty with blood collection. This survey identified the need for an innovative venous access strategy to better manage this group of patients. An external jugular venepuncture (EJV) protocol and education package was developed in collaboration with the Department of Anaesthetics, Gastroenterology and Liver Centre and HCV clinical nurse consultants (CNC). RPAH policy and procedure committee approved the protocol and patient information sheet. Patients with a history of difficulty with blood collection were eligible for the protocol. Patient satisfaction surveys were conducted. The initial survey of patients from the liver clinics and pharmacotherapy service identified that 48 percent had difficulty with blood collection from conventional sites. In the period October 2002 to July 2006, 29 patients (89 percent with history of IDU) were referred for EJV assessment. Major indications for EJV were for blood testing for initiation and monitoring of antiviral therapy and ongoing assessment of HCV infected patients. No adverse events resulted from the procedure. All patients surveyed report high levels of satisfaction with the technique compared to previous venous access attempts. EJV improves access to antiviral therapy and is a safe and effective technique for patients with difficult venous access (DVA). In addition, we have utilised EJV for post-transplant care of patients and used external jugular vein cannulation as vascular access for contrast imaging in hepatocellular carcinoma (HCC) assessment.