Is the HCV-HIV co-infection prevalence amongst injecting drug users a marker for the level of sexual and injection related HIV transmission?

BACKGROUND: Amongst injecting drug users (IDUs), HIV is transmitted sexually and parenterally, but HCV is transmitted primarily parenterally. We assess and model the antibody prevalence of HCV amongst HIV-infected IDUs (denoted as HCV-HIV co-infection prevalence) and consider whether it proxies the degree of sexual HIV transmission amongst IDUs. METHODS: HIV, HCV and HCV-HIV co-infection prevalence data amongst IDU was reviewed. An HIV/HCV transmission model was adapted. Multivariate model uncertainty analyses determined whether the model's ability to replicate observed data trends required the inclusion of sexual HIV transmission. The correlation between the model's HCV-HIV co-infection prevalence and estimated proportion of HIV infections due to injecting was evaluated. RESULTS: The median HCV-HIV co-infection prevalence (prevalence of HCV amongst HIV-infected IDUs) was 90% across 195 estimates from 43 countries. High HCV-HIV co-infection prevalences (>80%) occur in most (75%) settings, but can be lower in settings with low HIV prevalence (0.75). The model without sexual HIV transmission reproduced some data trends but could not reproduce any epidemics with high HIV/HCV prevalence ratios (>0.85) or low HCV-HIV co-infection prevalence (10%. The model with sexual HIV transmission reproduced data trends more closely. The proportion of HIV infections due to injecting correlated with HCV-HIV co-infection prevalence; suggesting that up to 80/60/90%. CONCLUSION: Substantial sexual HIV transmission may occur in many IDU populations; HCV-HIV co-infection prevalence could signify its importance

Is increased hepatitis C virus case-finding combined with current or 8-week to 12-week direct-acting antiviral therapy cost-effective in UK prisons? A prevention benefit analysis

UNLABELLED: Prisoners have a high prevalence of hepatitis C virus (HCV), but case-finding may not have been cost-effective because treatment often exceeded average prison stay combined with a lack of continuity of care. We assessed the cost-effectiveness of increased HCV case-finding and treatment in UK prisons using short-course therapies. A dynamic HCV transmission model assesses the cost-effectiveness of doubling HCV case-finding (achieved through introducing opt-out HCV testing in UK pilot prisons) and increasing treatment in UK prisons compared to status quo voluntary risk-based testing (6% prison entrants/year), using currently recommended therapies (8-24 weeks) or interferon (IFN)-free direct-acting antivirals (DAAs; 8-12 weeks, 95% sustained virological response, £3300/week). Costs (British pounds, £) and health utilities (quality-adjusted life years) were used to calculate mean incremental cost-effectiveness ratios (ICERs). We assumed 56% referral and 2.5%/25% of referred people who inject drugs (PWID)/ex-PWID treated within 2 months of diagnosis in prison. PWID and ex-PWID or non-PWID are in prison an average 4 and 8 months, respectively. Doubling prison testing rates with existing treatments produces a mean ICER of £19,850/quality-adjusted life years gained compared to current testing/treatment and is 45% likely to be cost-effective under a £20,000 willingness-to-pay threshold. Switching to 8-week to 12-week IFN-free DAAs in prisons could increase cost-effectiveness (ICER £15,090/quality-adjusted life years gained). Excluding prevention benefit decreases cost-effectiveness. If >10% referred PWID are treated in prison (2.5% base case), either treatment could be highly cost-effective (ICER<£13,000). HCV case-finding and IFN-free DAAs could be highly cost-effective if DAA cost is 10% lower or with 8 weeks' duration. CONCLUSIONS: Increased HCV testing in UK prisons (such as through opt-out testing) is borderline cost-effective compared to status quo voluntary risk-based testing under a £20,000 willingness to pay with current treatments but likely to be cost-effective if short-course IFN-free DAAs are used and could be highly cost-effective if PWID treatment rates were increased. (Hepatology 2016;63:1796-1808)

The role of a hepatitis C virus vaccine:modelling the benefits alongside direct-acting antiviral treatments

BACKGROUND: Hepatitis C virus (HCV) elimination is being seriously considered globally. Current elimination models require a combination of highly effective HCV treatment and harm reduction, but high treatment costs make such strategies prohibitively expensive. Vaccines should play a key role in elimination but their best use alongside treatments is unclear. For three vaccines with different efficacies we used a mathematical model to estimate the additional reduction in HCV prevalence when vaccinating after treatment; and to identify in which settings vaccines could most effectively reduce the number of treatments required to achieve fixed reductions in HCV prevalence among people who inject drugs (PWID). METHODS: A deterministic model of HCV transmission among PWID was calibrated for settings with 25, 50 and 75% chronic HCV prevalence among PWID, stratified by high-risk or low-risk PWID. For vaccines with 30, 60 or 90% efficacies, different rates of treatment and vaccination were introduced. We compared prevalence reductions achieved by vaccinating after treatment to prevent reinfection and vaccinating independently of treatment history in the community; and by allocating treatments and vaccinations to specific risk groups and proportionally across risk groups. RESULTS: Vaccinating after treatment was minimally different to vaccinating independently of treatment history, and allocating treatments and vaccinations to specific risk groups was minimally different to allocating them proportionally across risk groups. Vaccines with 30 or 60% efficacy provided greater additional prevalence reduction per vaccination in a setting with 75% chronic HCV prevalence among PWID than a 90% efficacious vaccine in settings with 25 or 50% chronic HCV prevalence among PWID. CONCLUSIONS: Vaccinating after treatment is an effective and practical method of administration. In settings with high chronic HCV prevalence among PWID, even modest coverage with a low-efficacy vaccine could provide significant additional prevalence reduction beyond treatment alone, and would likely reduce the cost of achieving prevalence reduction targets

Behavioural, not biological, factors drive the HCV epidemic among HIV-positive MSM: HCV and HIV modelling analysis including HCV treatment-as-prevention impact.

Background: Uncertainty surrounds why hepatitis C virus (HCV) is concentrated among HIV-positive men who have sex with men (MSM). We used mathematical modelling to explore reasons for these infection patterns, and implications for HCV treatment-as-prevention. Methods: Using a joint MSM HIV/HCV transmission model parameterized with UK behavioural data, we considered how biological (heightened HCV infectivity and reduced spontaneous clearance among HIV-positive MSM) and/or behavioural factors (preferential sexual mixing by HIV status and risk heterogeneity) could concentrate HCV infection in HIV-positive MSM as commonly observed (5-20 times the HCV prevalence in HIV-negative MSM; defined as the HCV ratio). We explored how HCV treatment-as-prevention impact varies under differing HCV ratios. Results: Biological factors produced low HCV ratios ( 10) that were highly sensitive to both factors. Irrespective of the HCV ratio or behavioural/biological factors, HCV treatment of HIV-diagnosed MSM markedly reduced the HCV prevalence among HIV-positive MSM, but less impact was achieved among all MSM for lower HCV ratios. Conclusions: Sexual behaviour patterns likely drive observed HCV infection patterns among HIV-positive MSM. Changes in these patterns could disseminate HCV amongst HIV-negative MSM, limiting the impact of targeting HCV treatment to HIV-diagnosed MSM

Interactive Software System Developed to Study How Icing Affects Airfoil Performance (Phase 1 Results)

SmaggIce (Surface Modeling and Grid Generation for Iced Airfoils), which is being developed at the NASA Glenn Research Center at Lewis Field, is an interactive software system for data probing, boundary smoothing, domain decomposition, and structured grid generation and refinement. All these steps are required for aerodynamic performance prediction using structured, grid-based computational fluid dynamics (CFD), as illustrated in the following figure. SmaggIce provides the underlying computations to perform these functions, as well as a graphical user interface to control and interact with them, and graphics to display the results

HIV treatment as prevention among people who inject drugs – a re-evaluation of the evidence

Background: Population-level associations between community measures of HIV viral load and HIV incidence have been interpreted as evidence for HIV anti-retroviral treatment (ART) as prevention among people who inject drugs (PWID). However, investigation of concurrent HCV and HIV incidence trends allows examination of alternative explanations for the fall in HIV incidence. We estimate the contribution of ART and reductions in injecting risk for reducing HIV incidence in Vancouver between 1996 and 2007. Methods: A deterministic model of HIV and HCV transmission among PWID was calibrated to the baseline (1996) HIV and HCV epidemic among PWID in Vancouver. While incorporating parameter uncertainty, the model projected what levels of ART protection and decreases in injecting risk could reproduce the observed reduction in HIV and HCV incidence for 1996–2007, and so what impact would have been achieved with just ART or just reductions in injecting risk. Results: Model predictions suggest the estimated reduction (84%) in HCV incidence for 1996–2007 required a 59% (2.5–97.5 percentile range 49–76%) reduction in injecting risk, which accounted for nine-tenths of the observed decrease in HIV incidence; the remainder was achieved with a moderate ART efficacy for reducing sexual HIV infectivity (70%, 51–89%) and an uncertain ART efficacy for reducing injection-related HIV infectivity (44%, 0–96%). Despite this uncertainty, projections suggest that the decrease in injecting risk reduced HIV incidence by 76% (63–85%) and ART further reduced HIV incidence by 8% (2–19%), or on its own by 3% (−34–37%). Conclusions: Observed declines in HIV incidence in Vancouver between 1996 and 2007 should be seen as a success for intensive harm reduction, whereas ART probably played a small role

Estimating the contribution of stimulant injection to HIV and HCV epidemics among people who inject drugs and implications for harm reduction:A modeling analysis

BACKGROUND: Stimulants, such as amphetamines and cocaine, are widely injected among people who inject drugs (PWID). Systematic reviews indicate stimulant injection is associated with HIV and HCV among PWID. Using these associations, we estimated the contribution of stimulant injection to HIV and HCV transmission among PWID. METHODS: We modeled HIV and HCV transmission among PWID, incorporating excess injecting and sexual risk among PWID who inject stimulants. We simulated three illustrative settings with different stimulants injected, prevalence of stimulant injecting, and HIV/HCV epidemiology. We estimated one-year population attributable fractions of stimulant injection on new HIV and HCV infections, and impact of scaling up needle-syringe programs (NSP). RESULTS: In low prevalence settings of stimulant injection (St. Petersburg-like, where 13% inject amphetamine), 9% (2.5-97.5% interval [95%I]: 6-15%) and 7% (95%I 4-11%) of incident HIV and HCV cases, respectively, could be associated with stimulant injection in the next year. With moderate stimulant injection (Montreal-like, where 34% inject cocaine), 29% (95%I: 19–37%) and 19% (95%I: 16-21%) of incident HIV and HCV cases, respectively, could be associated with stimulant injection. In high-burden settings like Bangkok where 65% inject methamphetamine, 23% (95%I:10–34%) and 20% (95%I: 9-27%) of incident HIV and HCV cases could be due to stimulant injection. High-coverage NSP (60%) among PWID who inject stimulants could reduce HIV (by 22-65%) and HCV incidence (by 7-11%) in a decade. DISCUSSION: Stimulant injection contributes substantially to HIV and HCV among PWID. NSP scale-up and development of novel interventions among PWID who inject stimulants are warranted

Financing essential HIV services: a new economic agenda.

Anna Vassall and colleagues discuss the need for, and challenges facing, innovative and sustainable financing of the HIV response. Please see later in the article for the Editors' Summary