Peter Vickerman

Prevention of HIV infection for people who inject drugs: why individual, structural, and combination approaches are needed

HIV can spread rapidly between people who inject drugs (through injections and sexual transmission), and potentially the virus can pass to the wider community (by sexual transmission). Here, we summarise evidence on the effectiveness of individual-level approaches to prevention of HIV infection; review global and regional coverage of opioid substitution treatment, needle and syringe programmes, and antiretroviral treatment; model the effect of increased coverage and a combination of these three approaches on HIV transmission and prevalence in injecting drug users; and discuss evidence for structural-level interventions. Each intervention alone will achieve modest reductions in HIV transmission, and prevention of HIV transmission necessitates high-coverage and combined approaches. Social and structural changes are potentially beneficial components in a combined-intervention strategy, especially when scale-up is difficult or reductions in HIV transmission and injection risk are difficult to achieve. Although further evidence is needed on how to optimise combinations of interventions in different settings and epidemics, we know enough now about which actions are effective: the challenge is to deliver these well and to scale.

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

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

3.2 million in Edinburgh and approximately

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.

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)

Opiate substitution treatment and HIV transmission in people who inject drugs: 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

Risk of death during and after opiate substitution treatment in primary care: prospective observational study in UK General Practice Research Database

3.2 million in Edinburgh and approximately

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

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)

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

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

Objective To quantify the effect of opiate substitution treatment in relation to HIV transmission among people who inject drugs. Design Systematic review and meta-analysis of prospective published and unpublished observational studies. Data sources Search of Medline, Embase, PsychINFO, and the Cochrane Library from the earliest year to 2011 without language restriction. Review methods We selected studies that directly assessed the impact of opiate substitution treatment in relation to incidence of HIV and studies that assessed incidence of HIV in people who inject drugs and that might have collected data regarding exposure to opiate substitution treatment but not have reported it. Authors of these studies were contacted. Data were extracted by two reviewers and pooled in a meta-analysis with a random effects model. Results Twelve published studies that examined the impact of opiate substitution treatment on HIV transmission met criteria for inclusion, and unpublished data were obtained from three additional studies. All included studies examined methadone maintenance treatment. Data from nine of these studies could be pooled, including 819 incident HIV infections over 23 608 person years of follow-up. Opiate substitution treatment was associated with a 54% reduction in risk of HIV infection among people who inject drugs (rate ratio 0.46, 95% confidence interval 0.32 to 0.67; P<0.001). There was evidence of heterogeneity between studies (I2=60%, χ2=20.12, P=0.010), which could not be explained by geographical region, site of recruitment, or the provision of incentives. There was weak evidence for greater benefit associated with longer duration of exposure to opiate substitution treatment. Conclusion Opiate substitution treatment provided as maintenance therapy is associated with a reduction in the risk of HIV infection among people who inject drugs. These findings, however, could reflect comparatively high levels of motivation to change behaviour and reduce injecting risk behaviour among people who inject drugs who are receiving opiate substitution treatment.

Global Estimates of Prevalent and Incident Herpes Simplex Virus Type 2 Infections in 2012

Objective To investigate the effect of opiate substitution treatment at the beginning and end of treatment and according to duration of treatment. Design Prospective cohort study. Setting UK General Practice Research Database Participants Primary care patients with a diagnosis of substance misuse prescribed methadone or buprenorphine during 1990-2005. 5577 patients with 267 003 prescriptions for opiate substitution treatment followed-up (17 732 years) until one year after the expiry of their last prescription, the date of death before this time had elapsed, or the date of transfer away from the practice. Main outcome measures Mortality rates and rate ratios comparing periods in and out of treatment adjusted for sex, age, calendar year, and comorbidity; standardised mortality ratios comparing opiate users’ mortality with general population mortality rates. Results Crude mortality rates were 0.7 per 100 person years on opiate substitution treatment and 1.3 per 100 person years off treatment; standardised mortality ratios were 5.3 (95% confidence interval 4.0 to 6.8) on treatment and 10.9 (9.0 to 13.1) off treatment. Men using opiates had approximately twice the risk of death of women (morality rate ratio 2.0, 1.4 to 2.9). In the first two weeks of opiate substitution treatment the crude mortality rate was 1.7 per 100 person years: 3.1 (1.5 to 6.6) times higher (after adjustment for sex, age group, calendar period, and comorbidity) than the rate during the rest of time on treatment. The crude mortality rate was 4.8 per 100 person years in weeks 1-2 after treatment stopped, 4.3 in weeks 3-4, and 0.95 during the rest of time off treatment: 9 (5.4 to 14.9), 8 (4.7 to 13.7), and 1.9 (1.3 to 2.8) times higher than the baseline risk of mortality during treatment. Opiate substitution treatment has a greater than 85% chance of reducing overall mortality among opiate users if the average duration approaches or exceeds 12 months. Conclusions Clinicians and patients should be aware of the increased mortality risk at the start of opiate substitution treatment and immediately after stopping treatment. Further research is needed to investigate the effect of average duration of opiate substitution treatment on drug related mortality.