Sharon J. Hutchinson

Hepatitis C virus treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals.

Substantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon‐free direct‐acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three‐quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale‐up to 15, 40, or 76 per 1,000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2‐, 13‐, and 15‐fold increases, respectively). Scale‐up to 22, 54, or 98 per 1,000 PWID annually could reduce prevalence by three‐quarters within 15 years. Less impact occurs with delayed scale‐up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of US

Meta-analysis of drug-related deaths soon after release from prison

3.2 million in Edinburgh and approximately

HCV treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals.

50 million in Melbourne and Vancouver. Conclusion: Interferon‐free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale‐up, and should be addressed. (Hepatology 2013;58:1598–1609)

The impact of needle and syringe provision and opiate substitution therapy on the incidence of Hepatitis C virus in injecting drug users: pooling of UK evidence.

Aims The transition from prison back into the community is particularly hazardous for drug-using offenders whose tolerance for heroin has been reduced by imprisonment. Studies have indicated an increased risk of drug-related death soon after release from prison, particularly in the first 2 weeks. For precise, up-to-date understanding of these risks, a meta-analysis was conducted on the risk of drug-related death in weeks 1 + 2 and 3 + 4 compared with later 2-week periods in the first 12 weeks after release from prison. Methods English-language studies were identified that followed up adult prisoners for mortality from time of index release for at least 12 weeks. Six studies from six prison systems met the inclusion criteria and relevant data were extracted independently. Results These studies contributed a total of 69 093 person-years and 1033 deaths in the first 12 weeks after release, of which 612 were drug-related. A three- to eightfold increased risk of drug-related death was found when comparing weeks 1 + 2 with weeks 3–12, with notable heterogeneity between countries: United Kingdom, 7.5 (95% CI: 5.7–9.9); Australia, 4.0 (95% CI: 3.4–4.8); Washington State, USA, 8.4 (95% CI: 5.0–14.2) and New Mexico State, USA, 3.1 (95% CI: 1.3–7.1). Comparing weeks 3 + 4 with weeks 5–12, the pooled relative risk was: 1.7 (95% CI: 1.3–2.2). Conclusions These findings confirm that there is an increased risk of drug-related death during the first 2 weeks after release from prison and that the risk remains elevated up to at least the fourth week.

Treatment of Hepatitis C Virus Infection Among People Who Are Actively Injecting Drugs: A Systematic Review and Meta-analysis

Substantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon‐free direct‐acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three‐quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale‐up to 15, 40, or 76 per 1,000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2‐, 13‐, and 15‐fold increases, respectively). Scale‐up to 22, 54, or 98 per 1,000 PWID annually could reduce prevalence by three‐quarters within 15 years. Less impact occurs with delayed scale‐up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of US

Can antiviral therapy for hepatitis C reduce the prevalence of HCV among injecting drug user populations? A modeling analysis of its prevention utility

3.2 million in Edinburgh and approximately

Cost‐effectiveness of hepatitis C virus antiviral treatment for injection drug user populations

50 million in Melbourne and Vancouver. Conclusion: Interferon‐free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale‐up, and should be addressed. (Hepatology 2013;58:1598–1609)

The Central Scotland Escherichia coli O157:H7 Outbreak: Risk Factors for the Hemolytic Uremic Syndrome and Death among Hospitalized Patients

AIMS To investigate whether opiate substitution therapy (OST) and needle and syringe programmes (NSP) can reduce hepatitis C virus (HCV) transmission among injecting drug users (IDUs). DESIGN Meta-analysis and pooled analysis, with logistic regression allowing adjustment for gender, injecting duration, crack injecting and homelessness. SETTING Six UK sites (Birmingham, Bristol, Glasgow, Leeds, London and Wales), community recruitment. PARTICIPANTS A total of 2986 IDUs surveyed during 2001-09. MEASUREMENT Questionnaire responses were used to define intervention categories for OST (on OST or not) and high NSP coverage (≥100% versus <100% needles per injection). The primary outcome was new HCV infection, measured as antibody seroconversion at follow-up or HCV antibody-negative/RNA-positive result in cross-sectional surveys. FINDINGS Preliminary meta-analysis showed little evidence of heterogeneity between the studies on the effects of OST (I2=48%, P=0.09) and NSP (I2=0%, P=0.75), allowing data pooling. The analysis of both interventions included 919 subjects with 40 new HCV infections. Both receiving OST and high NSP coverage were associated with a reduction in new HCV infection [adjusted odds ratios (AORs)=0.41, 95% confidence interval (CI): 0.21-0.82 and 0.48, 95% CI: 0.25-0.93, respectively]. Full harm reduction (on OST plus high NSP coverage) reduced the odds of new HCV infection by nearly 80% (AOR=0.21, 95% CI: 0.08-0.52). Full harm reduction was associated with a reduction in self-reported needle sharing by 48% (AOR 0.52, 95% CI: 0.32-0.83) and mean injecting frequency by 20.8 injections per month (95% CI: -27.3 to -14.4). CONCLUSIONS There is good evidence that uptake of opiate substitution therapy and high coverage of needle and syringe programmes can substantially reduce the risk of hepatitis C virus transmission among injecting drug users. Research is now required on whether the scaling-up of intervention exposure can reduce and limit hepatitis C virus prevalence in this population.

Combination Interventions to Prevent HCV Transmission Among People Who Inject Drugs: Modeling the Impact of Antiviral Treatment, Needle and Syringe Programs, and Opiate Substitution Therapy

BACKGROUND Although guidelines recommend that people who inject drugs (PWID) should not be excluded from hepatitis C (HCV) treatment, some services remain reluctant to treat PWID. The aim of this review was to investigate sustained virologic response (SVR), adherence, discontinuation, and HCV reinfection among PWID. METHODS A search of Medline, Embase, and Cochrane databases (between 2002 and January 2012) was conducted for primary articles/conference abstracts examining HCV treatment outcomes in PWID. Meta-analysis was used to obtain pooled estimates of SVR, adherence, discontinuation, and HCV reinfection. RESULTS Ten primary articles and 1 conference abstract met the inclusion criteria. Across 6 studies (comprising 314 drug users, of whom 141 [45%] were PWID), pooled SVR was 56% (95% confidence interval [CI], 50%-61%) for all genotypes, 37% (95% CI, 26%-48%) for genotypes 1/4, and 67% (95% CI, 56%-78%) for genotypes 2/3. Pooled 80/80/80 adherence was 82% (95% CI, 74%-89%) across 2 studies, and pooled treatment discontinuation was 22% (95% CI, 16%-27%) across 4 studies. Across 5 studies (comprising 131 drug users) examining reinfection, pooled risk was 2.4 (95% CI, .9-6.1) per 100 person-years. CONCLUSIONS HCV treatment outcomes are acceptable in PWID, supporting treatment guidelines. The pooled estimate of HCV reinfection risk was low, but there was considerable uncertainty around this estimate. Further studies on the risk of reinfection are needed to assess the long-term effectiveness of HCV treatment in PWID.

Influence of Alcohol on the Progression of Hepatitis C Virus Infection: A Meta-analysis

BACKGROUND & AIMS Hepatitis C virus antiviral treatment is effective for individual patients but few active injecting drug users are treated. We considered the utility of antiviral treatment for primary prevention of hepatitis C. METHODS A hepatitis C transmission model among injecting drug users was developed, incorporating treatment (62.5% average sustained viral response) with no retreatment after initial treatment failure, potential re-infection for those cured, equal genotype setting (genotype 1:genotype 2/3), and no immunity. In addition, we examined scenarios with varied treatment response rates, immunity, or retreatment of treatment failures. RESULTS In the baseline scenario, annually treating 10 infections per 1000 injecting drug users results in a relative decrease in hepatitis C prevalence over 10 years of 31%, 13%, or 7% for baseline (untreated endemic chronic infection) prevalences of 20%, 40%, or 60%, respectively. Sensitivity analyses show that including the potential for immunity has minimal effect on the predictions; prevalence reductions remain even if SVR is assumed to be 25% lower among active IDU than current evidence suggests; retreatment of treatment failures does not alter the short-term (<5 years) projections, but does increase treatment gains within 20 years; hepatitis C free life years gained from treating active injecting drug users are projected to be higher than from treating non-injecting drug users for prevalences below 60%. CONCLUSIONS Despite the possibility of re-infection, modest rates of hepatitis C treatment among active injecting drug users could effectively reduce transmission. Evaluating and extending strategies to treat hepatitis C among active injectors are warranted.