Community-based, point-of-care hepatitis C testing: perspectives and preferences of people who inject drugs.

A barrier to hepatitis C treatment for people who inject drugs (PWID) is needing to attend multiple appointments for diagnosis. Point-of-care hepatitis C tests provide results within 20 to 105 minutes and can be offered opportunistically in nonclinical settings such as needle syringe programmes. In this nested qualitative study, we explored the acceptability of point-of-care testing for PWID. PWID attending participating needle syringe programmes were screened using the OraQuick HCV antibody mouth swab (result in 20 minutes); those with a reactive result then underwent venepuncture for a point-of-care RNA test: the Xpert HCV Viral Load (result in 105 minutes). Convenience sampling was used to select participants for a semi-structured interview. A hybrid thematic analysis was performed, guided by Sekhon's "Theoretical Framework of Acceptability." Nineteen participants were interviewed. Three core themes emerged: "people and place," "method of specimen collection," and "rapidity of result return." It was highly acceptable to be offered testing at the needle syringeprogrammes by nurses and community health workers, who were described as competent and nonjudgemental. Most participants reported that even if a finger-stick point-of-care RNA test were an option in the future, they would prefer venepuncture, as the sample could be used for pre-treatment workup and bundled testing. Waiting 20 minutes to receive the antibody test result was acceptable, whereas the 105 minutes required for the RNA result was unacceptable. Offering point-of-care hepatitis C testing at needle syringe programmes is acceptable to PWID, however tests that avoid venepuncture are not necessarily the most attractive to PWID.

Current and emerging antiviral treatments for hepatitis C infection.

Newly licensed direct acting antivirals for hepatitis C virus HCV are able to cure up to 75% of patients chronically infected with genotype-1 infection, which is the predominant HCV strain in Europe and North America. Emerging antiviral therapies promise further increases in virological response, as well as improved tolerability, reduced duration of therapy, and will potentially eliminate the need for interferon use. This review highlights the main therapeutic agents used in current standard of care, including telaprevir and boceprevir. It goes on to evaluate the mechanisms of emerging drugs, their stage of development and response rates seen in research to date. Finally, it projects into the not too distant future to consider treatment strategies involving combinations of agents and interferon-free therapies, and in which patients they might prove most successful.

Assessing the cost-effectiveness of treating chronic hepatitis C virus in people who inject drugs in Australia.

BACKGROUND AND AIM: To assess the cost-effectiveness of hepatitis C virus treatment with pegylated interferon alfa-2a and ribavirin in current and former people who inject drugs (PWID). METHODS: A decision analytic model simulated the lifetime costs and outcomes of four treatment options: early treatment with mild fibrosis, standard treatment with moderate fibrosis, late treatment with compensated cirrhosis, and no treatment. Treatment modalities were simulated across current, former, and never-injector cohorts of 1000 hypothetical patients with chronic hepatitis C virus. The main outcome measures were incremental costs ($AUD) per quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICERs) were calculated for each cohort. RESULTS: Treatment of current PWID during mild fibrosis resulted in a discounted average gain of 1.60 QALYs (95% confidence interval 0.93-2.26) for an added cost of $12,723 ($11,153-$14,396) compared with no treatment, yielding an ICER of $7941 per QALY gained ($6347-$12,017). Former PWID gained 1.80 QALYs (1.29-2.33) for $10,441 ($8843-$12,074) for early treatment compared with no treatment, resulting in an ICER of $5808 per QALY gained ($5189-$6849). Never-injectors gained 2.33 QALYs (1.87-2.80) for $9290 ($7642-$10,912) compared with no treatment-an ICER of $3985 per QALY gained ($3896-$4080). Early treatment was more cost-effective than late treatment in all cohorts. CONCLUSIONS: Despite comorbidities, increased mortality, and reduced adherence, treatment of both current and former PWID is cost-effective. Our estimates fall below the unofficial Australian cost-effectiveness threshold of $AUD 50,000 per QALY for public subsidies. Scaling up treatment for PWID can be justified on purely economic grounds.

Modelling antiviral treatment to prevent hepatitis C infection among people who inject drugs in Victoria, Australia.

OBJECTIVES: To develop a mathematical model to project the potential impact of hepatitis C virus (HCV) treatment on HCV infection prevalence among people who inject drugs (PWID). DESIGN AND SETTING: An existing model of HCV transmission among PWID was parameterised using data from Victoria, Australia, including specific parameter estimates of the number of people who are currently active injecting drug users, average duration of injecting, chronic HCV infection prevalence among PWID, annual mortality, and annual HCV treatment rate. We also explored the impact of prevalence uncertainty, program scale-up, and new treatments. MAIN OUTCOME MEASURE: Prevalence of chronic HCV infection among people who are currently active injecting drug users. RESULTS: With annual treatment rates of 13, 17, or 25 per 1000 PWID, the model predicts relative prevalence reductions of 20%, 30%, and 50%, respectively, within 30 years. If new treatments giving higher sustained viral response rates are available in 5 years, estimated impact is increased by 21%­23% at 15 years, and 17%­38% at 30 years, depending on treatment rates. CONCLUSIONS: This model suggests that modest rates of current HCV treatment among PWID in Victoria, Australia could halve HCV infection prevalence among PWID in 30 years. This finding suggests that interventions aimed at increasing access to HCV treatment in community clinics will benefit individual PWID and reduce HCV infection prevalence.

Quality of Life and Social Functioning during Treatment of Recent Hepatitis C Infection: A Multi-Centre Prospective Cohort.

AIM: Despite effective treatment for recent hepatitis C (HCV) infection, side-effects and adherence concerns limit its use among people who inject drugs (PWID). This study evaluated health-related quality of life (HRQoL) and social functioning following infection and during recent HCV treatment. METHODS: The Australian Trial of Acute Hepatitis C studied the natural history and treatment of recent HCV infection. HRQoL (SF-12v2) and social functioning (Opiate Treatment Index score) were measured over 48 weeks and their impact on treatment uptake, adherence and virological response were assessed. RESULTS: Of 163 participants, 111 received treatment (HCV n = 74, SVR 55%; HCV/HIV n = 37, SVR 74%). 116 (71%) were male, 124 (76%) ever injected drugs, with 55 (36%) injecting recently and 28/55 (51%) reported needle/syringe sharing. At baseline, median physical and mental HRQoL was 54 units (IQR 46-58) and 46 (35-54) (reference median: 50), respectively, and median social functioning score was 11 units (7-17). Higher social function (<10 vs ≥15) predicted increased treatment uptake (AOR 3.43, 95%CI 1.01-11.6, p = 0.048) and higher SVR (AOR 5.11, 95%CI 1.30-20.15, p = 0.020). After adjustment, treated participants had lower physical (-4.90 units, 95%CI -6.33 to -3.48, p<0.001) and mental HRQoL (-3.7 units, 95%CI -5.55 to -1.86, p<0.001) at on-treatment visits, but HRQoL returned to baseline levels during follow-up. CONCLUSIONS: Social functioning can predict recent HCV treatment uptake and SVR. Efforts to maximise social stability may improve treatment response. Pegylated-interferon treatment is associated with reduced HRQoL on-treatment in an already vulnerable population of PWID that would be better served by interferon-free regimens particularly in treated target at PWID to prevent transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00192569.

The role of viral and host genetics in natural history and treatment of chronic HCV infection.

Understanding of the natural history and treatment responsiveness of chronic hepatitis C virus (HCV) infection has evolved rapidly in recent years. Advances in HCV molecular virology and host genetics can now better predict spontaneous clearance and treatment outcomes. HCV genotype is the most important viral factor predicting interferon-α treatment responsiveness; HCV-1 subtype is emerging as a key determinant of the efficacy of direct acting antiviral therapy. Genome-wide association studies have recently identified several clinically important host determinants of the outcomes of peginterferon-α and ribavirin treatment outcome: IL28B polymorphism is associated with spontaneous clearance and treatment responsiveness; ITPA polymorphism protects against ribavirin-induced anaemia and dose reductions; genetic determinants of liver fibrosis progression rate have been proposed. In this review, we evaluate the role of viral and host genetics in the natural history and treatment outcomes of chronic HCV infection, and consider how this knowledge might help individualize clinical management in the era of DAA therapy.

Recruitment and follow-up of injecting drug users in the setting of early hepatitis C treatment: insights from the ATAHC study.

Despite current injecting drug users (IDUs) being the major risk group for new hepatitis C virus (HCV) infections in most countries, they constitute a small minority of study populations in almost all studies of acute HCV infection treatment. The Australian Trial in Acute Hepatitis C (ATAHC) is examining natural history and treatment efficacy among predominantly IDU-acquired acute HCV. Recruitment is through an Australian network of primary and tertiary care sites. Eligible participants are offered treatment with pegylated-interferon alpha-2a (PEG-IFN) for 24 weeks, with both treated and untreated participants followed for up to three years. Quantitative and qualitative data on injecting behaviour is collected on study participants. Participants are regularly reviewed by a multidisciplinary team that includes the treating clinician, HCV clinic nurse, outreach worker and when necessary are referred to a drug and alcohol worker, social worker, psychiatrist or other appropriate services. A contact log records all interactions between participants and the study team. In September 2006, 121 subjects had been screened, 107 were enrolled and 75 had chosen to commence a 24-week course of PEG-IFN (HIV/HCV coinfected participants are treated with PEG-IFN/ribavirin combination therapy). Eighty per cent of ATAHC participants reported IDU within the previous six months. Recruitment is planned to continue through mid-2007. Through a series of case reports, this paper describes factors that are potential barriers to recruitment, follow-up, and treatment of IDUs in the context of acute HCV infection. PEG-IFN adherence and toxicity, current substance use or mental health issues are not presenting as the only barriers to HCV treatment. Financial and transport difficulties, isolation and social support, and legal issues have been prominent and had the potential to impact on clinic attendance and treatment success. Our work suggests that by using a multidisciplinary approach, potential barriers to recruitment and follow-up of current IDUs to HCV treatment can be effectively addressed, and this highly marginalised population can be successfully engaged and treated.