Network‐based recruitment of people who inject drugs for hepatitis C testing and linkage to care

Although oral direct‐acting agent (DAA) therapies have the potential to reduce the burden of hepatitis C virus (HCV) infection, treatment uptake remains low, particularly among people who inject drugs (PWID). This study examined the feasibility of an innovative peer‐based recruitment strategy to engage PWID in HCV testing and treatment. We interviewed an initial set of HCV antibody‐positive PWID as ‘primary indexes’ to gather demographic, drug use, health information and drug network characteristics. Primary indexes were then briefly educated on HCV and its treatment and encouraged to recruit their injection drug ‘network members’ for HCV testing and linkage to care. Eligible network members were enrolled as ‘secondary indexes’ and completed the same index study procedures. In sum, 17 of 36 primary indexes initiated the recruitment of 64 network members who were HCV antibody positive and eligible to become indexes. In multivariable analysis, successful recruitment of at least one network member was positively associated with prior HCV treatment (OR 2.80; CI [1.01, 7.72]), daily or more injection drug use (OR 2.38; CI [1.04, 5.47]), and a higher number of injection drug network members (OR 1.20; CI [1.01, 1.42]). Among the 69 participants with chronic HCV not previously linked to HCV care at enrolment, 91% (n = 63) completed a linkage to HCV care appointment, 45% (n = 31) scheduled an appointment with an HCV provider, and 20% (n = 14) initiated HCV therapy. These findings suggest a potential benefit for peer‐driven, network‐based interventions focused on HCV treatment‐experienced PWID as a mechanism to increase HCV linkage to care.     

Innovative technologies for point‐of‐care testing of viral hepatitis in low‐resource and decentralized settings

According to the Global Burden of Diseases, chronic viral hepatitis B and C are one of the most challenging global health conditions that rank among the first causes of morbidity and mortality worldwide. Low‐ and middle‐income countries are particularly affected by the health burden associated with HBV or HCV infection. One major gap in efficiently addressing the issue of viral hepatitis is universal screening. However, the costs and chronic lack of human resources for using traditional screening strategies based on serology and molecular biology preclude any scaling‐up. Point‐of‐care tests have been deemed a powerful potential solution to fill the current diagnostics gap in low‐resource and decentralized settings. Despite high interest resulting from their development in recent years, very few point‐of‐care devices have reached the market. Scaling down and automating all testing steps in 1 single device (eg, sample preparation, detection and readout) is indeed challenging. But innovations in multiple disciplines such as nanotechnologies, microfluidics, biosensors and synthetic biology have led to the creation of chip‐sized laboratory systems called “lab‐on‐a‐chip” devices. This review aims to explain how these innovations can overcome technological barriers that usually arise for each testing step while developing integrated point‐of‐care tests. Point‐of‐care test prototypes rarely meet the requirements for mass production, which also hinders their large‐scale production. In addition to logistical hurdles, legal and economic constraints specific to the commercialization of in vitro diagnostics, which have also participated in the low transfer of innovative point‐of‐care tests to the field, are discussed.     

Hepatitis C virus testing,liver disease assessment and treatment uptake among people who inject drugs pre‐ and post‐universal access to direct‐acting antiviral treatment in Australia: The LiveRLife study

Gaps in hepatitis C virus (HCV) testing, diagnosis, liver disease assessment and treatment uptake among people who inject drugs (PWID) persist. We aimed to describe the cascade of HCV care among PWID in Australia, prior to and following unrestricted access to direct‐acting antiviral (DAA) treatment. Participants enrolled in an observational cohort study between 2014 and 2018 provided fingerstick whole‐blood samples for dried blood spot, Xpert HCV Viral Load and venepuncture samples. Participants underwent transient elastography and clinical assessment by a nurse or general practitioner. Among 839 participants (mean age 43 years), 66% were male (n = 550), 64% (n = 537) injected drugs in the previous month, and 67% (n = 560) reported currently receiving opioid substitution therapy. Overall, 45% (n = 380) had detectable HCV RNA, of whom 23% (n = 86) received HCV treatment within 12 months of enrolment. HCV treatment uptake increased from 2% in the pre‐DAA era to 38% in the DAA era. Significant liver fibrosis (F2‐F4) was more common in participants with HCV infection (38%) than those without (19%). Age 50 years or older (aOR, 2.88; 95% CI, 1.18‐7.04) and attending a clinical follow‐up with nurse (aOR, 3.19; 95% CI, 1.61‐6.32) or physician (aOR, 11.83; 95% CI, 4.89‐28.59) were associated with HCV treatment uptake. Recent injection drug use and unstable housing were not associated with HCV treatment uptake. HCV treatment uptake among PWID has increased markedly in the DAA era. Evaluation of innovative and simplified models of care is required to further enhance treatment uptake.     

Improving access to care for people who inject drugs: Qualitative evaluation of project ITTREAT—An integrated community hepatitis C service

Achieving hepatitis C virus (HCV) elimination by 2030 requires an increased linkage to care for people who inject drugs (PWID). Project ITTREAT was established to mitigate barriers to HCV care by providing an integrated service within a local drug and alcohol treatment centre. This study aimed to explore the experiences of clients and staff involved in Project ITTREAT and assess the facilitators and barriers to a community‐based HCV service. Between October 2014 and April 2016, drug and alcohol treatment attendees were interviewed using one‐to‐one semi‐structured interviews. Drug and alcohol treatment staff took part in focus groups. All data were recorded, transcribed verbatim and analysed using thematic content analysis. Fifteen drug and alcohol treatment attendees with current/previous HCV infection were interviewed, and 15 staff members contributed across two focus groups. Drug and alcohol treatment staff and attendees reported that Project ITTREAT facilitated access to HCV care by mitigating previous negative hospital‐based experiences. Other key facilitators were positive narratives around HCV care, and drug and alcohol treatment attendees being well engaged in their drug/alcohol recovery. Barriers included a lack of stability in drug and alcohol treatment attendees, negative discourse around testing/treatment and stigma associated with attending the drug and alcohol treatment to access HCV treatment in some who had successfully achieved drug rehabilitation. Our findings indicate the positive impact of an integrated and personalized community‐based service delivered by a dedicated hepatitis nurse. This played a crucial role in reducing barriers to HCV care for PWID. Our work also highlights areas for future investment including non–DAT‐based community services and increasing awareness of new treatments amongst this cohort.     

Effectiveness and cost‐effectiveness of interventions targeting harm reduction and chronic hepatitis C cascade of care in people who inject drugs: The case of France

Direct‐acting antivirals (DAAs) represent an opportunity to improve hepatitis C virus (HCV) care cascade. This combined with improved harm reduction interventions may lead to HCV elimination especially in people who inject drugs (PWID). We assessed the effectiveness/cost‐effectiveness of improvements in harm reduction and chronic hepatitis C (CHC) care cascade in PWID in France. We used a dynamic model of HCV transmission and CHC natural history and evaluated the following: improved needle/syringe programmes‐opioid substitution therapies, faster diagnosis/linkage to care, earlier treatment initiation, alone and in combination among active PWID (mean age = 36). Outcomes were as follows: life expectancy in discounted quality‐adjusted life years (QALYs); direct lifetime discounted costs; incremental cost‐effectiveness ratio (ICER); number of infections/reinfections. Under the current practice, life expectancy was 15.846 QALYs, for a mean lifetime cost of €20 762. Treatment initiation at F0 fibrosis stage alone was less effective and more costly than faster diagnosis/linkage to care combined with treatment initiation at F0, which increased life expectancy to 16.694 QALYs, decreased new infections by 37%, with a ICER = €5300/QALY. Combining these interventions with harm reduction improvements was the most effective scenario (life expectancy = 16.701 QALYs, 41% decrease in new infections) but was not cost‐effective (ICER = €105 600/QALY); it became cost‐effective with higher initial HCV incidence rates and lower harm reduction coverage than in our base‐case scenario. This study illustrated the high effectiveness, and cost‐effectiveness, of a faster diagnosis/linkage to care together with treatment from F0 with DAAs. This “Test and treat” strategy should play a central role both in improving the life expectancies of HCV‐infected patients, and in reducing HCV transmission.     

Integrated supervised consumption services and hepatitis C testing and treatment among people who inject drugs in Toronto,Canada: A cross-sectional analysis

Despite the availability of publicly funded hepatitis C (HCV) treatment in Canada, treatment gaps persist, particularly among people who inject drugs. We estimate correlates of HCV care cascade engagement (testing, diagnosis, and treatment) among people who inject drugs in Toronto, Canada and examine the effect of accessing differing supervised consumption service (SCS) models on self-reported HCV testing and treatment. This is a cross-sectional baseline analysis of 701 people who inject drugs surveyed in the Toronto, Ontario integrated Supervised Injection Services (OiSIS-Toronto) study between November 2018 and March 2020. We examine correlates of self-reported HCV care cascade outcomes including SCS model, demographic, socio-structural, drug use, and harm reduction characteristics. Overall, 647 participants (92%) reported ever receiving HCV testing, of whom 336 (52%) had been diagnosed with HCV. Among participants who reported ever being diagnosed with HCV, 281 (84%) reported chronic HCV, of whom 130 (46%) reported HCV treatment uptake and 151 (54%) remained untreated. Compared to those with no SCS use, participants who had ever injected at an integrated SCS model with co-located HCV care had greater prevalence of both ever receiving HCV testing (adjusted prevalence ratio [aPR]: 1.12, 95% confidence interval [CI]: 1.02–1.24) and ever receiving HCV treatment (aPR: 1.67, 95% CI: 1.04–2.69). Over half of participants diagnosed with chronic HCV reported remaining untreated. Our findings suggest that integrated SCS models with co-located HCV care represent key strategies for linkage to HCV care, but that more is needed to support scale-up.     

A simple and inexpensive point‐of‐care test for hepatitis B surface antigen detection: serological and molecular evaluation

Early identification of chronic hepatitis B is important for optimal disease management and prevention of transmission. Cost and lack of access to commercial hepatitis B surface antigen (HBsAg) immunoassays can compromise the effectiveness of HBV screening in resource‐limited settings and among marginalized populations. High‐quality point‐of‐care (POC) testing may improve HBV diagnosis in these situations. Currently available POC HBsAg assays are often limited in sensitivity. We evaluated the NanoSign^® HBs POC chromatographic immunoassay for its ability to detect HBsAg of different genotypes and with substitutions in the ‘a’ determinant. Thirty‐seven serum samples from patients with HBV infection, covering HBV genotypes A–G, were assessed for HBsAg titre with the Roche Elecsys HBsAg II quantification assay and with the POC assay. The POC assay reliably detected HBsAg at a concentration of at least 50 IU/mL for all genotypes, and at lower concentrations for some genotypes. Eight samples with substitutions in the HBV ‘a’ determinant were reliably detected after a 1/100 dilution. The POC strips were used to screen serum samples from 297 individuals at risk for HBV in local clinical settings (health fairs and outreach events) in parallel with commercial laboratory HBsAg testing (Quest Diagnostics EIA). POC testing was 73.7% sensitive and 97.8% specific for detection of HBsAg. Although the POC test demonstrated high sensitivity over a range of genotypes, false negatives were frequent in a clinical setting. Nevertheless, the POC assay offers advantages for testing in both developed and resource‐limited countries due to its low cost (0.50$) and immediately available results.     

Increasing hepatitis C virus screening in people who inject drugs in Switzerland using rapid antibody saliva and dried blood spot testing: A cost‐effectiveness analysis

People who inject drugs (PWID) are a key high‐risk group for Hepatitis C Virus (HCV) infection due to the sharing of needles and drug‐preparation equipment. However, only approximately 50% of PWID are currently screened for HCV in Switzerland. At present, screening of PWID occurs in general practice via venepuncture. Compared to venepuncture, screening via rapid antibody saliva and dried blood spot (DBS) tests is well adapted to PWID, who typically have difficult venous access. The cost‐effectiveness of an increased access screening programme of PWID (increased screening using rapid antibody saliva tests and DBS tests [semi‐quantitative viraemia and viral genotype]) was analysed through a decision tree screening model combined with the outputs of a Markov treatment model. Sensitivity and scenario analyses examined the uncertainty of results. At a willingness to pay (WTP) threshold of CHF 100 000 (USD 105 000) per quality‐adjusted life year (QALY), the increased access screening programme was cost‐effective compared to current screening, with a base case incremental cost‐effectiveness ratio of CHF 7 940 (USD 8337) per QALY. The net monetary benefit was CHF 959 802 668 (USD 1 007 792 801) for the PWID population and CHF 94 469 (USD 99 192) per person. The increased access screening programme had a 97.0% probability of being cost‐effective compared to the current screening method at the WTP threshold of CHF 100 000 (USD 105 000). The results showed an increased access screening programme that uses tests which are better suited to the PWID population to be more cost‐effective, due to the increased uptake that rapid antibody saliva and DBS tests generate.     

Venous access and care: harnessing pragmatics in harm reduction for people who inject drugs

Aim To explore the facilitators of long‐term hepatitis C avoidance among people who inject drugs. Design We employed a qualitative life history design. Setting Recruitment took place through low‐threshold drug services and drug user networks in South East and North London. Participants were interviewed at the recruitment services or in their homes. Participants The sample comprised 35 people who inject drugs, 20 of whom were hepatitis C antibody‐negative. Participants' average injecting trajectory was 19 years (6–33), with 66% primarily injecting heroin, and 34% a crack and heroin mix. Nine (26%) of the sample were female and the average age was 39 years (23–53). Measurements Two interviews were conducted with each participant, with the second interview incorporating reference to a computer‐constructed life history time‐line. Interview accounts were audiorecorded, transcribed verbatim and analysed thematically. Findings Hepatitis C risk awareness was recent and deprioritized by the majority of participants. The facilitation of venous access and care was an initial and enduring rationale for safe injecting practices. Difficult venous access resulted in increased contamination of injecting environments and transitions to femoral injecting. Participants expressed an unmet desire for non‐judgemental venous access information and advice. Conclusions Harm reduction interventions which attend to the immediate priorities of people who inject drugs, such as venous access and care, have the potential to re‐engage individuals who are jaded or confused by hepatitis C prevention messages.     

Point‐of‐care testing of neonatal coagulation

The aim of this validation study was to compare prothrombin time (PT) and activated partial thromboplastin time (APTT) results from a point‐of‐care testing (POCT) device (Rapidpoint Coag) with those from standard laboratory tests. The subjects were newborn infants needing coagulation screen for any clinical indications within a regional neonatal intensive care unit. The level of agreement between POCT and laboratory measurements of PT and APTT was determined. For PT: the bias was from ?7.6 to 12.4 s and precision was 5.0 s. For the detection of prolonged PT at a level of 16 s, the sensitivity was 0.70, specificity was 0.57 and the positive predictive value (PPV) was 0.62. For APTT: the bias was from ?39.1 to 23.7 s, and precision was 15.7 s. For the detection of prolonged APTT at a level of 55 s, the sensitivity was 0.80, specificity was 0.95 and the PPV was 0.80. The POCT device tested has limited utility as a cot‐side device for screening for a prolongation of the APTT in the newborn but is not sensitive for screening for prolongation of the PT.