Preservation of functionality, immunophenotype, and recovery of HIV RNA from PBMCs cryopreserved for more than 20 years.

Background: Many research laboratories have long-term repositories of cryopreserved peripheral blood mononuclear cells (PBMC), which are costly to maintain but are of uncertain utility for immunological studies after decades in storage. This study investigated preservation of cell surface phenotypes and in-vitro functional capacity of PBMC from viraemic HIV+ patients and healthy seronegative control subjects, after more than 20 years of cryopreservation. Methods: PBMC were assessed by 18-colour flow cytometry for major lymphocyte subsets within T, B, NK, and dendritic cells and monocytes. Markers of T-cell differentiation and activation were compared with original immunophenotyping performed in 1995/1996 on fresh blood at the time of collection. Functionality of PBMC was assessed by culture with influenza antigen or polyclonal T-cell activation, to measure upregulation of activation-induced CD25 and CD134 (OX40) on CD4 T cells and cytokine production at day 2, and proliferative CD25+ CD4 blasts at day 7. RNA was extracted from cultures containing proliferating CD4+ blast cells, and intracellular HIV RNA was measured using short amplicons for both the Double R and pol region pi code assays, whereas long 4-kbp amplicons were sequenced. Results: All major lymphocyte and T-cell subpopulations were conserved after long-term cryostorage, except for decreased proportions of activated CD38+HLA-DR+ CD4 and CD8 T cells in PBMC from HIV+ patients. Otherwise, differences in T-cell subpopulations between recent and long-term cryopreserved PBMC primarily reflected donor age-associated or HIV infection-associated effects on phenotypes. Proportions of naïve, memory, and effector subsets of T cells from thawed PBMC correlated with results from the original flow cytometric analysis of respective fresh blood samples. Antigen-specific and polyclonal T-cell responses were readily detected in cryopreserved PBMC from HIV+ patients and healthy control donors. Intracellular HIV RNA quantitation by pi code assay correlated with original plasma viral RNA load results. Full-length intracellular and supernatant-derived amplicons were generated from 5/12 donors, and sequences were ≥80% wild-type, consistent with replication competence. Conclusions: This unique study provides strong rationale and validity for using well-maintained biorepositories to support immunovirological research even decades after collection.

Acute Q fever in patients with an influenza-like illness in regional New South Wales, Australia.

INTRODUCTION: Query (Q) fever is a zoonosis caused by the bacterium Coxiella burnetii typically presenting as an influenza-like illness (ILI) with or without hepatitis. The infection may be missed by clinicians in settings of low endemicity, as the presentation is clinically not specific, and there are many more common differential diagnoses for ILI including SARS-CoV-2 infection. METHODS: Residual serum samples were retrospectively tested for Phase 1 and 2 Q fever-specific IgM, IgG, IgA antibodies by indirect immunofluorescence and C. burnetii DNA by polymerase chain reaction. They had not been previously tested for Q fever, originating from undiagnosed patients with probable ILI, aged 10-70 years and living in regional New South Wales, Australia. The results were compared with contemperaneous data on acute Q fever diagnostic tests which had been performed based on clinicians requests from a geographically similar population. RESULTS: Only one (0.2%) instance of missed acute Q fever was identified after testing samples from 542 eligible patients who had probable ILI between 2016-2023. Laboratory data showed that during the same period, 731 samples were tested for acute Q fever for clinician-initiated requests and of those 70 (9.6%) were positive. Probability of being diagnosed with Q fever after a clinician initiated request was similar regardless of the patients sex, age and the calendar year of sampling. CONCLUSION: In this sample, Q fever was most likely to be diagnosed via clinician requested testing rather than by testing of undiagnosed patients with an influenza like illness.

Hepatitis C treatment outcome among people in prison: The SToP-C study.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) burden is higher among people in prison given high prevalence of injecting drug use. This study evaluated direct-acting antiviral (DAA) treatment outcome in prisons. METHODS: The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study enrolled individuals incarcerated in four Australian prisons (2017-2019). Participants with detectable HCV RNA were offered sofosbuvir-velpatasvir for 12 weeks. Sustained virological response (SVR) was assessed in intention-to-treat (ITT; participants commencing treatment and due for SVR assessment before study close) and per-protocol (PP; participants with documented treatment completion and SVR assessment) populations. RESULTS: Among 799 participants with HCV, 324 (41%) commenced treatment (94% male; median age, 32 years; median duration of incarceration, 9 months). In ITT population (n = 310), 201 had documented treatment completion (65% [95% CI: 59-70]), and 137 achieved SVR (ITT-SVR: 44% [95% CI: 39-50]). In PP population (n = 143), 137 achieved SVR (PP-SVR: 96% [95% CI: 91-98]). Six participants had quantifiable HCV RNA at SVR assessment from treatment failure (n = 2) or reinfection (n = 4). Release or inter-prison transfer was common reasons for no documented treatment completion (n = 106/109 [97%]) and no SVR assessment (n = 57/58 [98%]). In ITT analysis, longer incarceration was associated with increased SVR (adjusted OR per month 1.03 [95% CI: 1.01-1.04]). CONCLUSION: Among participants who completed DAA treatment and were assessed for SVR, treatment outcome was consistent with non-prison clinical studies. However, most individuals did not complete treatment or lacked study-documented treatment outcome due to release or transfer. Strategies to accommodate dynamic prisoner populations are required to ensure continuity of HCV care, including treatment completion and post-treatment care.

Using nominal group technique with people who are incarcerated in Canadian federal prisons to identify barriers and solutions to improving Prison Needle Exchange Program uptake.

BACKGROUND: Prison needle exchange programs (PNEPs) are a critical component for harm reduction in prisons. Little is known about the PNEP access barriers for people who are incarcerated, but the low uptake in the Canadian program highlights these constraints. We aimed to identify the barriers and potential solutions for increasing PNEP coverage in the nine Canadian federal prisons where they operate. METHODS: Eighteen focus groups were conducted in nine prisons using nominal group technique (NGT) with two stakeholders: peer advocates and people who use or identified as potential users of the PNEP. NGT uses a round-robin technique followed by generating a list of barriers to PNEP enrolment within their prison. Participants then allocated votes to rank the highest priority barriers, followed by an identical process to generate solutions to address the top three barriers. Interview transcripts describing participant narratives during this process were de-identified and coded to generated themes. Barriers and solutions receiving >10 % of votes within respective participant groups, alongside associated narratives, are discussed more fully. RESULTS: Fear of repercussions due to drug use, lack of confidentiality, and fear of being targeted and sanctioned by correctional authorities were perceived by both stakeholder groups as the top barriers inhibiting PNEP enrolment. Stigma (peer advocates) and the application process for the program (PNEP users) were also ranked as a priority. Proposed solutions included education and external oversight of PNEP (i.e., not via correctional officers) by both groups. Peer advocates regarded improving participant confidentiality and a supervised/safe injection site as potential enablers for program participation, while PNEP users identified wrap-around services as likely to improve access. CONCLUSION: Barriers to increasing PNEP coverage in Canadian federal prisons proposed by participants highlight the importance of trust and perceived repercussions surrounding program participation. These barriers and proposed solutions highlight a need for changes in implementation to PNEP delivery if the potential health benefits of PNEPs are to be realised.

Understanding hepatitis C virus (HCV) health literacy and educational needs among people in prison to enhance HCV care in prisons.

BACKGROUND: Hepatitis C virus (HCV) is a significant concern within prison populations. Provision of HCV testing and treatment for people in prison is expanding and a key component of global elimination efforts. Despite growing service availability, several challenges remain in HCV testing and treatment engagement during incarceration. The PIVOT study demonstrated that a 'one-stop-shop' intervention (point-of-care HCV RNA testing, Fibroscan®, nurse-led clinical assessment, and fast-tracked direct-acting antiviral prescription) enhanced HCV testing and treatment at a reception prison in Australia. Utilising Squier et al's Health Literacy Skills Framework, this analysis aimed to understand HCV health literacy and educational needs among people at a reception prison in Australia. METHODS: Semi-structured interviews were conducted with twenty-four male PIVOT study participants. Purposive sampling ensured comparable representation of those with: 1) prior HCV testing history (standard pathology / no prior testing), and 2) injecting drug use history (IDU; ever / never). RESULTS: Varied HCV health literacy levels and educational needs were evident amongst people in prison. Whilst those with multiple incarceration episodes and IDU history (prior knowledge) appeared to have stronger HCV health literacy than those without, substantial gaps in HCV health literacy were evident. Knowledge of HCV transmission risks in prison was high, and most understood the importance of HCV testing and treatment in prison (comprehension), but ability to engage with HCV testing and treatment services, participation in safe injecting behaviours (health-related behaviours), and knowledge of re-infection and re-treatment, within the context of the prison environment, were suboptimal. There was a general desire for increased HCV education in prison. CONCLUSION: Gaps in HCV health literacy among people in prison were evident, indicating opportunities for improvement. A targeted HCV education program for people in prison, addressing the gaps identified in this analysis, may enhance HCV testing, treatment, and prevention by fostering stronger HCV health literacy among people in prison.

Using nominal group technique to identify perceived barriers and facilitators to improving uptake of the Prison Needle Exchange Program in Canadian federal prisons by correctional officers and healthcare workers.

BACKGROUND: Elimination of bloodborne viruses including HIV and hepatitis C virus from prisons requires high coverage of evidence-based interventions that prevent bloodborne virus transmission, including needle and syringe programs. Canada launched a Prison Needle Exchange Program (PNEP) in nine federal prisons in 2018; however, uptake among people who inject drugs in prison remains low. We aimed to explore barriers and facilitators to improving PNEP uptake identified by correctional officers and healthcare workers. METHODS: Participants from nine federal prisons with PNEP completed focus groups using nominal group technique, a rapid mixed-method consensus strategy. Responses were generated, rank-ordered, and prioritized by each stakeholder group. We identified the highest-ranking responses (≥10 % of the overall votes) to questions about barriers and facilitators to PNEP uptake. RESULTS: Between September 2023 and February 2024, 16 focus groups were conducted with 118 participants (n = 51 correctional officers; n = 67 healthcare workers). Among correctional officers, the top perceived barriers were bullying from peers (22 %), fear of being targeted by correctional officers (14 %), and fear of repercussions due to drug use (13 %). The top facilitators were safe injection sites (30 %), provision of wrap-around services (16 %), and education of correctional officers (10 %). Among healthcare workers, the top perceived barriers were lack of confidentiality (16 %), fear of being targeted by correctional officers (12 %), and a long and complex application process (11 %). The top facilitators were education of correctional officers (29 %), delivery of PNEP by an external provider (15 %), automatic approval for participation in the PNEP (13 %), and safe injection sites (12 %). CONCLUSION: Multiple modifiable barriers and solutions to improving PNEP uptake in Canadian federal prisons were identified by correctional employees. Both participant groups identified the potential for safe injection sites and education to correctional officers as enabling PNEP uptake. These data will inform Canadian efforts to improve engagement and to expand PNEP coverage.

Development of an evidence-based hepatitis C education program to enhance public health literacy in the Australian prison sector: The Hepatitis in Prisons Education program (HepPEd).

BACKGROUND: Australia's prisons have a high chronic hepatitis C (HCV) prevalence (8 %). Antiviral therapies and prison-based hepatitis services are available, but only a minority of those eligible are being treated. Improving the HCV public health literacy of the prison sector via targeted education may overcome key barriers to scale-up treatment. This paper describes the: i) HCV public health literacy of the prison setting; ii) barriers and solutions for HCV education and service engagement; iii) HCV education program co-design and development processes; and iv) HepPEd resources. METHODS: A national needs assessment was conducted to analyse the HCV public health literacy of the target audience groups in the prisons (healthcare providers; custodial officers; people in prison) to inform development of a prison-specific HCV education program (HepPEd). Structured interviews were conducted with key informants (n = 40). Three National Steering Committees, one for each target group, were convened to co-design and develop HepPEd. RESULTS: Only healthcare providers involved with hepatitis care were considered to have 'good' to 'very good' HCV health literacy (including knowledge, attitudes, and capabilities), with all other groups considered less favourably. Key barriers identified included being time poor (healthcare providers), poor motivation (custodial officers) and stigma (people in prison). Peer education delivery was considered a key facilitator for custodial officers and people in prison. A suite of multi-modal resources addressing the perceived gaps in HCV health literacy was developed, with a broad theme of 'Let's talk about hep C'. Delivery of HepPEd was designed to overcome key barriers and utilise facilitators for each group. CONCLUSIONS: Significant gaps in HCV health literacy were perceived amongst the target audience groups. The comprehensive co-design and development processes utilised in HepPEd suggest the program will be well-placed to improve the HCV public health literacy of the prison sector and thereby enhance HCV testing and treatment rates amongst people in prison.

Discovery of a monoclonal, high-affinity CD8+ T-cell clone following natural hepatitis C virus infection.

CD8+ T cells recognizing their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide-major histocompatibility complex (pMHC) complex. Advances in single-cell sequencing have increased accessibility toward identifying TCRs with matched antigens. Here we present the discovery of a monoclonal CD8+ T-cell population with specificity for a hepatitis C virus (HCV)-derived human leukocyte antigen (HLA) class I epitope (HLA-B*07:02 GPRLGVRAT) which was isolated directly ex vivo from an individual with an episode of acutely resolved HCV infection. This population was absent before infection and underwent expansion and stable maintenance for at least 2 years after infection as measured by HLA-multimer staining. Furthermore, the monoclonal clonotype was characterized by an unusually long dissociation time (half-life = 794 s and koff = 5.73 × 10-4) for its target antigen when compared with previously published results. A comparison with related populations of HCV-specific populations derived from the same individual and a second individual suggested that high-affinity TCR-pMHC interactions may be inherent to epitope identity and shape the phenotype of responses which has implications for rational TCR selection and design in the age of personalized immunotherapies.

Controlling COVID-19 outbreaks in the correctional setting: A mathematical modelling study.

Correctional centres (termed here 'prisons') are at high risk of COVID-19 and have featured major outbreaks worldwide. Inevitable close contacts, frequent inmate movements, and a disproportionate burden of co-morbidities mean these environments need to be prioritised in any public health response to respiratory pathogens such as COVID-19. We developed an individual-based SARS-CoV-2 transmission model for the prison system in New South Wales, Australia - incorporating all 33 correctional centres, 13,458 inmates, 578 healthcare and 6,909 custodial staff. Potential COVID-19 disease outbreaks were assessed under various mitigation strategies, including quarantine on entry, isolation of cases, rapid antigen testing of staff, as well as immunisation.Without control measures, the model projected a peak of 472 new infections daily by day 35 across the prison system, with all inmates infected by day 120. The most effective individual mitigation strategies were high immunisation coverage and prompt lockdown of centres with infected inmates which reduced outbreak size by 62-73%. Other than immunisation, the combination of quarantine of inmates at entry, isolation of proven or suspected cases, and widespread use of personal protective equipment by staff and inmates was the most effective strategy. High immunisation coverage mitigates the spread of COVID-19 within and between correctional settings but is insufficient alone. Maintaining quarantine and isolation, along with high immunisation levels, will allow correctional systems to function with a low risk of outbreaks. These results have informed public health policy for respiratory pathogens in Australian correctional systems.

B-cell characteristics define HCV reinfection outcome.

BACKGROUND & AIMS: In individuals highly exposed to HCV, reinfection is common, suggesting that natural development of sterilising immunity is difficult. In those that are reinfected, some will develop a persistent infection, while a small proportion repeatedly clear the virus, suggesting natural protection is possible. The aim of this study was to characterise immune responses associated with rapid natural clearance of HCV reinfection. METHODS: Broad neutralising antibodies (nAbs) and Envelope 2 (E2)-specific memory B cell (MBC) responses were examined longitudinally in 15 individuals with varied reinfection outcomes. RESULTS: Broad nAb responses were associated with MBC recall, but not with clearance of reinfection. Strong evidence of antigen imprinting was found, and the B-cell receptor repertoire showed a high level of clonality with ongoing somatic hypermutation of many clones over subsequent reinfection events. Single-cell transcriptomic analyses showed that cleared reinfections featured an activated transcriptomic profile in HCV-specific B cells that rapidly expanded upon reinfection. CONCLUSIONS: MBC quality, but not necessarily breadth of nAb responses, is important for protection against antigenically diverse variants, which is encouraging for HCV vaccine development. IMPACT AND IMPLICATIONS: HCV continues to have a major health burden globally. Limitations in the health infrastructure for diagnosis and treatment, as well as high rates of reinfection, indicate that a vaccine that can protect against chronic HCV infection will greatly complement current efforts to eliminate HCV-related disease. With alternative approaches to testing vaccines, such as controlled human inoculation trials under consideration, we desperately need to identify the correlates of immune protection. In this study, in a small but rare cohort of high-risk injecting drug users who were reinfected multiple times, breadth of neutralisation was not associated with ultimate clearance of the reinfection event. Alternatively, characteristics of the HCV-specific B-cell response associated with B-cell proliferation were. This study indicates that humoral responses are important for protection and suggests that for genetically very diverse viruses, such as HCV, it may be beneficial to look beyond just antibodies as correlates of protection.

Preparing correctional settings for the next pandemic: a modeling study of COVID-19 outbreaks in two high-income countries.

Introduction: Correctional facilities are high-priority settings for coordinated public health responses to the COVID-19 pandemic. These facilities are at high risk of disease transmission due to close contacts between people in prison and with the wider community. People in prison are also vulnerable to severe disease given their high burden of co-morbidities. Methods: We developed a mathematical model to evaluate the effect of various public health interventions, including vaccination, on the mitigation of COVID-19 outbreaks, applying it to prisons in Australia and Canada. Results: We found that, in the absence of any intervention, an outbreak would occur and infect almost 100% of people in prison within 20 days of the index case. However, the rapid rollout of vaccines with other non-pharmaceutical interventions would almost eliminate the risk of an outbreak. Discussion: Our study highlights that high vaccination coverage is required for variants with high transmission probability to completely mitigate the outbreak risk in prisons.

Challenges and facilitators in repeated bio-behavioural surveys for blood-borne virus infections in Australian prisons.

BACKGROUND: Prison-based blood-borne virus (BBV) surveillance is essential for evaluation of prevention and treatment programs for high-risk populations, such as people who inject drugs who are over-represented amongst those incarcerated. Regular triennial surveillance has been in place in Australian prisons for almost two decades, but has been focused to date only on new prison entrants. Recently, the Australian Hepatitis and risk survey in prisons (AusHep study) was established to provide improved surveillance via an expanded bio-behavioural survey representative of all people in prison, including those sentenced and those on remand. This paper aims to identify the challenges and facilitators in conducting bio-behavioural surveys for BBV infections in prison settings. METHODS: Randomly selected individuals in 23 prisons, representative of prisons and people in prison (male/female, security classification, rural location, Aboriginal or Torres Strait Islander), were offered point-of-care testing for HIV and hepatitis C (HCV) antibodies, hepatitis B virus surface (HBs) antigen, and HCV RNA (if HCV antibody positive). Data regarding risk behaviours, harm reduction measures, and prior BBV testing and treatment were collected by interview. Data was also collected on the challenges and facilitators encountered during planning and implementation at each participating prison. RESULTS: In the first round, AusHep recruited 1599 participants (98 % participation, 89 % male, median age 35 years, 49 % ever injected drugs). Major implementation challenges included: slow and complex ethics and governance requirements in each jurisdiction, and challenging logistical arrangements and participant access constraints in the prisons. Major facilitators included use of point-of-care testing allowing immediate feedback of results, strong support from jurisdictional stakeholders in correction and public health sectors, flexibility in the timing and detailed planning for each site, and computer tablet-based data collection. CONCLUSION: The high participation and informative findings indicated clear feasibility of this improved surveillance system. Strong stakeholder engagement and flexibility in logistics facilitated successful implementation of multi-jurisdictional prison-based surveillance.

People in community corrections are a population with unmet need for viral hepatitis care.

To reach World Health Organization elimination targets for hepatitis C, different strategies are needed to reach people who have not yet been diagnosed and treated. In the context of declining treatment initiation rates, innovation in service design and delivery is necessary: testing and treatment needs to be offered to people in non-traditional settings. The community corrections (probation and parole) population is larger than the prison population, which has high prevalence of hepatitis C and-in some countries-established diagnosis and treatment programs. In this Viewpoint we identify a gap in hepatitis C care for people under community correctional supervision, a group who have either never been imprisoned or need continuity of healthcare provided in prison. We propose that offering hepatitis C screening and treatment would benefit this population, and accelerate progress to hepatitis C elimination.

Barriers and advocacy needs for hepatitis C services in prisons: Informing the prisons hepatitis C advocacy toolkit.

BACKGROUND: Carceral settings are a key focus of the 2030 WHO global hepatitis C virus (HCV) elimination goals. Despite this, access to HCV testing and treatment services in prisons remains low globally, limiting opportunities to achieve these goals. Advocacy efforts are needed to address service inequities and mobilise support for enhanced HCV programs in prisons globally. INHSU Prisons, a special interest group of the International Network on Health and Hepatitis in Substance Users (INHSU) is developing a Prisons HCV Advocacy Toolkit to address this need. Here we present findings of a mixed study to inform the development of the Toolkit. METHODS: The aim of this study was to inform the development of the Toolkit, including understanding barriers for scaling up prison-based HCV services globally and advocacy needs to address these. An online survey (n = 181) and in-depth interviews (n = 25) were conducted with key stakeholders from countries of different economic status globally. Quantitative data were statistically analysed using R Studio and qualitative data were analysed thematically. The data sets were merged using a convergent design. RESULTS: Key barriers for enhanced prison-based HCV services included lack of political will and action, lack of prison-based healthcare resources, and poor awareness about HCV and the importance of prison-based HCV services. These findings underscore how advocacy efforts are needed to motivate policymakers to prioritise HCV healthcare in prisons and ensure funds are available for services (including diagnostic tools and treatment, healthcare teams to implement services, and systems to measure their success). Advocacy resources to raise the awareness of policy makers, people working in the prison sector, and incarcerated populations were also identified as key to increasing HCV service uptake. CONCLUSION: The Toolkit has the potential to support advocacy efforts for reaching HCV elimination targets. By understanding the advocacy needs of potential Toolkit end-users, the findings can inform its development and increase its accessibility, acceptability, and uptake for a globally diverse audience.

Scale-up of Direct-Acting Antiviral Treatment in Prisons Is Both Cost-effective and Key to Hepatitis C Virus Elimination.

Background: The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study demonstrated that scaling up of direct-acting antiviral (DAA) treatment reduced hepatitis C virus (HCV) transmission. We evaluated the cost-effectiveness of scaling up HCV treatment in statewide prison services incorporating long-term outcomes across custodial and community settings. Methods: A dynamic model of incarceration and HCV transmission among people who inject drugs (PWID) in New South Wales, Australia, was extended to include former PWID and those with long-term HCV progression. Using Australian costing data, we estimated the cost-effectiveness of scaling up HCV treatment in prisons by 44% (as achieved by the SToP-C study) for 10 years (2021-2030) before reducing to baseline levels, compared to a status quo scenario. The mean incremental cost-effectiveness ratio (ICER) was estimated by comparing the differences in costs and quality-adjusted life-years (QALYs) between the scale-up and status quo scenarios over 40 years (2021-2060) discounted at 5% per annum. Univariate and probabilistic sensitivity analyses were performed. Results: Scaling up HCV treatment in the statewide prison service is projected to be cost-effective with a mean ICER of A$12 968/QALY gained. The base-case scenario gains 275 QALYs over 40 years at a net incremental cost of A$3.6 million. Excluding DAA pharmaceutical costs, the mean ICER is reduced to A$6 054/QALY. At the willingness-to-pay threshold of A$50 000/QALY, 100% of simulations are cost-effective at various discount rates, time horizons, and changes of treatment levels in prison and community. Conclusions: Scaling up HCV testing and treatment in prisons is highly cost-effective and should be considered a priority in the national elimination strategy. Clinical Trials Registration: NCT02064049.

Characterization of antibody-dependent cellular phagocytosis in patients infected with hepatitis C virus with different clinical outcomes.

Early neutralizing antibodies against hepatitis C virus (HCV) and CD8 + T cell effector responses can lead to viral clearance. However, these functions alone are not sufficient to protect patients against HCV infection, thus undefined additional antiviral immune mechanisms are required. In recent years, Fc-receptor-dependent antibody effector functions, particularly, antibody-dependent cellular phagocytosis (ADCP) were shown to offer immune protection against several RNA viruses. However, its development and clinical role in patients with HCV infection remain unknown. In this study, we found that patients with chronic GT1a or GT3a HCV infection had significantly higher concentrations of anti-envelope 2 (E2) antibodies, predominantly IgG1 subclass, than patients that cleared the viruses while the latter had antibodies with higher affinities. 97% of the patients with HCV had measurable ADCP of whom patients with chronic disease showed significantly higher ADCP than those who naturally cleared the virus. Epitope mapping studies showed that patients with antibodies that target antigenic domains on the HCV E2 protein that are known to associate with neutralization function are also strongly associated with ADCP, suggesting antibodies with overlapping/dual functions. Correlation studies showed that ADCP significantly correlated with plasma anti-E2 antibody levels and neutralization function regardless of clinical outcome and genotype of infecting virus, while a significant correlation between ADCP and affinity was only evident in patients that cleared the virus. These results suggest ADCP was mostly driven by antibody titer in patients with chronic disease while maintained in clearers due to the quality (affinity) of their anti-E2 antibodies despite having lower antibody titers.

Trends in intravenous immunoglobulin use in New South Wales, Australia.

BACKGROUND: Intravenous immunoglobulin (IVIg) is a critical replacement therapy for immunodeficiencies and immunomodulatory treatment for autoimmune and inflammatory diseases. Adequate supply of IVIg is a global issue, necessitating supply restrictions. In Australia, despite strict criteria for use, demand for IVIg has increased over time and exceeds domestic supply. OBJECTIVE: Factors associated with the upward trend in overall IVIg use were examined, including in the number of unique patients, IVIg dosing and treatment frequency and variations by prescribing discipline and disease group. METHODS: De-identified data of IVIg dispensed in the largest Australian state (New South Wales) from 2007 to 2013 were provided by Australian Red Cross Lifeblood. Trends and projections were calculated using log-linear regression of unique patients, treatment episodes and grams of IVIg for overall use and use stratified by discipline and disease group. RESULTS: During the study period, 169 453 treatment episodes were recorded for 12 547 unique patients accounting for 5 827 787 g of IVIg use. Overall, IVIg use increased by 12.0% (11.5-12.6%) per year representing a 97.7% increase (91.6-104%) over the study period. The highest growth was among neurological conditions (16.0% (14.9-17.1%) per year). An increase in the number of unique patients was the primary driver of this growth, augmented by increases in the frequency and average dose per treatment. CONCLUSIONS: Clinically acceptable measures to improve management of IVIg supply are needed including optimising dose, frequency and duration of treatment. Formal evaluation of IVIg versus alternatives, including cost-effectiveness and comparative efficacy, is warranted.

Incidence of hepatitis C virus infection in the prison setting: The SToP-C study.

People in prison are at high risk of HCV given high injecting drug use prevalence. This study evaluated HCV incidence and associated injecting drug use characteristics in prison. The SToP-C study enrolled people incarcerated in four Australian prisons. Participants were tested for HCV at enrolment and then every 3-6 months (October-2014 to November-2019). Participants eligible for this analysis included those at-risk of HCV primary infection (anti-HCV negative) or re-infection (anti-HCV positive, HCV RNA negative) with follow-up assessment. A total of 1643 eligible participants were included in analyses (82% male; median age 33 years; 30% injected drugs in prison; 1818 person-years of follow-up). Overall HCV incidence was 6.11/100 person-years (95%CI: 5.07-7.35), with higher rate of re-infection (9.34/100 person-years; 95%CI: 7.15-12.19) than primary infection (4.60/100 person-years; 95%CI: 3.56-5.96). In total population (n = 1643), HCV risk was significantly higher among participants injecting drugs in prison [vs. no injecting; adjusted hazard ratio (aHR): 10.55, 95%CI: 5.88-18.92), and those who were released and re-incarcerated during follow-up (vs. remained incarcerated; aHR: 1.60, 95%CI: 1.03-2.49). Among participants who injected recently (during past month, n = 321), HCV risk was reduced among those receiving high-dosage opioid agonist therapy (OAT), i.e. methadone ≥60 mg/day or buprenorphine ≥16 mg/day, (vs. no OAT, aHR: 0.11, 95%CI: 0.02-0.80) and increased among those sharing needles/syringes without consistent use of disinfectant to clean injecting equipment (vs. no sharing, HR: 4.60, 95%CI: 1.35-15.66). This study demonstrated high HCV transmission risk in prison, particularly among people injecting drugs. High-dosage OAT was protective, but improved OAT coverage and needle/syringe programmes to reduce sharing injecting equipment are required.