Effect of integrated hepatitis C virus treatment on psychological distress in people with substance use disorders.

People with substance use disorders (SUD) have a high prevalence of chronic hepatitis C virus (HCV) infection and mental health disorders. We aimed to assess the impact of integrated HCV treatment on psychological distress measured by Hopkins-symptom-checklist-10 (SCL-10). This multi-center randomized controlled trial evaluated psychological distress as a secondary outcome of integrated HCV treatment (INTRO-HCV trial). From 2017 to 2019, 289 participants were randomly assigned to receive either integrated or standard HCV treatment with direct-acting antiviral therapy. Integrated HCV treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in internal medicine outpatient clinics at centralized hospitals. Participants in the integrated treatment arm had a sustained virologic response of 93% compared to 73% for those in standard treatment arm. Psychological distress was assessed using SCL-10 prior to initiation of HCV treatment and 12 weeks after treatment completion. The mean SCL-10 score prior to HCV treatment was 2.2 (standard deviation [SD]: 0.7) for patients receiving integrated HCV treatment and 2.2 (SD: 0.8) for those receiving standard HCV treatment. Twelve weeks after the end of treatment, the mean SCL-10 score change was - 0.1 (- 0.3;0.0) in the integrated compared to the standard arm. Psychological distress did not substantially change during the treatment period and was not significantly different between the treatment arms.

Estimates of hepatitis B virus prevalence among general population and key risk groups in EU/EEA/UK countries: a systematic review.

BackgroundThe burden of chronic hepatitis B virus (HBV) varies across the European Union (EU) and European Economic Area (EEA).AimWe aimed to update the 2017 HBV prevalence estimates in EU/EEA countries and the United Kingdom for 2018 to 2021.MethodsWe undertook a systematic review, adding to HBV prevalence estimates from an existing (2005-2017) database. Databases were searched for original English-language research articles including HBV surface antigen prevalence estimates among the general population, pregnant women, first-time blood donors (FTB), men who have sex with men (MSM), migrants and people in prison. Country experts contributed grey literature data. Risk of bias was assessed using a quality assessment framework.FindingsThe update provided 147 new prevalence estimates across the region (updated total n = 579). Median HBV prevalence in the general population was 0.5% and the highest was 3.8% (Greece). Among FTB, the highest prevalence was 0.8% (Lithuania). Estimates among pregnant women were highest in Romania and Italy (5.1%). Among migrants, the highest estimate was 31.7% (Spain). Relative to 2017 estimates, median prevalence among pregnant women decreased by 0.5% (to 0.3%) and increased by 0.9% (to 5.8%) among migrants. Among MSM, the highest estimate was 3.4% (Croatia). Prevalence among people in prison was highest in Greece (8.3%) and the median prevalence increased by 0.6% (to 2.1%).ConclusionsThe HBV prevalence is low in the general population and confined to risk populations in most European countries with some exceptions. Screening and treatment should be targeted to people in prison and migrants.

Trends in HIV incidence following scale-up of harm reduction interventions among people who inject drugs in Kachin, Myanmar, 2008-2020: analysis of a retrospective cohort dataset.

Background: People who inject drugs (PWID) in Kachin, Myanmar, have a high HIV prevalence (>40%), but there is no data on incidence. We used HIV testing data from three harm reduction drop-in centres (DIC) in Kachin (2008-2020) to determine HIV incidence trends among PWID and associations with intervention uptake. Methods: Individuals were HIV-tested at first DIC visit and periodically thereafter, during which demographic and risk behaviour data were collected. Two DIC provided opioid agonist therapy (OAT) from 2008. Monthly DIC-level needle/syringe provision (NSP) data was available from 2012. Site-level 6-monthly NSP coverage was denoted low, high, or medium if it was below the lower quartile, above upper quartile, between these quartiles of provision levels over 2012-2020, respectively. HIV incidence was estimated by linking subsequent test records for those initially testing HIV-negative. Associations with HIV incidence were examined using Cox regression. Findings: Follow-up HIV testing data was available for 31.4% (2227) of PWID initially testing HIV-negative, with 444 incident HIV infections during 6266.5 person years (py) of follow-up. Overall HIV incidence was 7.1 per 100 py (95% confidence interval 6.5-7.8), which decreased from 19.3 (13.3-28.2) in 2008-11 to 5.2 per 100 py (4.6-5.9) in 2017-20. In the full PWID incidence dataset after adjustment for various factors, recent (≤6 weeks) injecting (aHR 1.74, 1.35-2.25) and needle sharing (aHR 2.00, 1.48-2.70) were associated with higher incidence, while longer injection careers were associated with reduced incidence (aHR 0.54, 0.34-0.86, for 2-5 yrs vs <2 yrs). In a reduced dataset including data on OAT access and NSP coverage (2012-2020 for two DIC providing OAT), being on OAT during follow-up was associated with reduced HIV incidence (aHR 0.36, 0.27-0.48, compared to never being on OAT) as was high NSP coverage (aHR 0.64, 0.48-0.84, compared to medium syringe coverage). Interpretation: Although HIV incidence is high among PWID in Kachin, data suggests it has decreased since the scale-up in harm reduction interventions. Funding: US NIH, Médecins du Monde.

The efficacy of integrated hepatitis C virus treatment in relieving fatigue in people who inject drugs: a randomized controlled trial.

BACKGROUND: Most people who inject drugs (PWIDs) suffer from severe fatigue, and chronic hepatitis C virus (HCV) infection may play a role in this. However, there is scarce evidence about interventions that alleviate fatigue among PWIDs. The present study investigated the effect of integrated HCV treatment on fatigue in this population compared to the effect of standard HCV treatment, adjusted for sustained virological response of the HCV treatment. METHODS: This multi-center, randomized controlled trial evaluated fatigue as a secondary outcome of integrated HCV treatment (the INTRO-HCV trial). From May 2017 to June 2019, 276 participants in Bergen and Stavanger, Norway, were randomly assigned to receive integrated and standard HCV treatment. Integrated treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in specialized infectious disease outpatient clinics at referral hospitals. Fatigue was assessed prior to treatment and 12 weeks after treatment using the nine-item Fatigue Severity Scale (FSS-9). We applied a linear mixed model to evaluate the impact of integrated HCV treatment on changes in FSS-9 (ΔFSS-9) sum scores. RESULTS: At baseline, the mean FSS-9 sum score was 46 (standard deviation (SD): 15) for participants on integrated HCV treatment and 41 (SD: 16) for those on standard treatment. Twelve weeks after completed HCV treatment, the mean FSS-9 sum score for participants receiving integrated HCV treatment was 42 (SD: 15) and 40 (SD: 14) for those receiving standard HCV treatment. Integrated HCV treatment did not reduce the FSS-9 scores compared to standard HCV treatment (ΔFSS-9: -3.0, 95% confidence interval (CI): -6.4;0.4). CONCLUSIONS: Fatigue is a common symptom among PWIDs. Integrated HCV treatment is at least equal to standard HCV treatment in improving fatigue. TRIAL REGISTRATION: ClinicalTrials.gov.no NCT03155906, 16/05/2017.

Risk factors of HIV and variation in access to clean needles among people who inject drugs in Pakistan.

We identified key risk factors for HIV among people who inject drugs (PWID) in Pakistan and explored access to free clean needles. Multivariable logistic regression was used to investigate associations between HIV prevalence and demographic, behavioral, and socio-economic characteristics of PWID. Data came from the Government of Pakistan's Integrated Biological and Behavioral Surveillance (IBBS) Round 5 (2016-17; 14 cities). A secondary analysis investigated associations with reported access to clean needles. Unweighted HIV prevalence among 4,062 PWID (99% male) was 21.0%. Longer injecting duration (Odds ratio [OR] 1.06 [95% confidence interval: 1.02-1.10]; per year), higher injecting frequency (OR 1.67 [1.30-2.13]; per unit increase), and injecting heroin (OR 1.90 [1.11-3.25]) were positively associated with HIV prevalence. There was no association between using a used syringe at last injection and HIV. Having>10 years of education had lower odds of HIV than being illiterate (OR 0.58 [0.35-0.95]). Having a regular sexual partner (OR 0.74 [0.57-0.97]) or paying for sex with the opposite sex (OR = 0.62 [0.45-0.85]) had lower odds of HIV than not. Conversely, PWID paying a man/hijra for sex had higher odds of HIV (OR 1.20 [1.00-1.43]). Receipt of clean needles varied by city of residence (0-97% coverage), whilst PWID with knowledge of HIV service delivery programs had higher odds of receiving clean needles (OR 4.58 [3.50-5.99]). Injecting behaviors were associated with HIV prevalence among PWID, though risks related to paying for sex remain complicated. Geographical variation in access to clean needles suggests potential benefits of more widely spread public health services.

Key MessagesWhat is already known on this topicThe HIV epidemic in Pakistan is concentrated among key populations including people who inject drugs.What this study addsInjecting practices, sexual behaviors, and socio-economic factors are associated with HIV prevalence among people who inject drugs. Access to harm reduction services is varied in Pakistan.How this study might affect research, practice, or policyAccess to clean free needles, as well as service delivery programs, with a broad geographical reach remain important to curb the HIV epidemic among people who inject drugs in Pakistan.

Incidence of HIV and hepatitis C virus among people who inject drugs, and associations with age and sex or gender: a global systematic review and meta-analysis.

BACKGROUND: Measuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender. METHODS: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42020220884. FINDINGS: Our updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987-2021 for HIV and 1992-2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3-2·3; I2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I2=66·9%) and HCV (1·5, 1·3-1·8; I2=70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1-1·6; I2=55·3%) and HCV (1·2, 1·1-1·3; I2=43·3%) acquisition than men. For both HIV and HCV, the median risk-of-bias score was 6 (IQR 6-7), indicating moderate risk. INTERPRETATION: Although sparse, available HIV and HCV incidence estimates offer insights into global levels of HIV and HCV transmission among PWID. Intensified efforts are needed to keep track of the HIV and HCV epidemics among PWID and to expand access to age-appropriate and gender-appropriate prevention services that serve young PWID and women who inject drugs. FUNDING: Canadian Institutes of Health Research, Fonds de recherche du Québec-Santé, Canadian Network on Hepatitis C, UK National Institute for Health and Care Research, and WHO.

Prison-based interventions are key to achieving HCV elimination among people who inject drugs in New South Wales, Australia: A modelling study.

BACKGROUND & AIMS: People who inject drugs (PWID) experience high incarceration rates which are associated with increased hepatitis C virus (HCV) transmission risk. We assess the importance of prison-based interventions for achieving HCV elimination among PWID in New South Wales (NSW), Australia. METHODS: A model of incarceration and HCV transmission among PWID was calibrated in a Bayesian framework to epidemiological and incarceration data from NSW, incorporating elevated HCV acquisition risk among recently released PWID. We projected the contribution of differences in transmission risk during/following incarceration to HCV transmission over 2020-2029. We estimated the past and potential future impact of prison-based opioid agonist therapy (OAT; ~33% coverage) and HCV treatment (1500 treatments in 2019 with 32.9%-83.3% among PWID) on HCV transmission. We estimated the time until HCV incidence reduces by 80% (WHO elimination target) compared to 2016 levels with or without prison-based interventions. RESULTS: Over 2020-2029, incarceration will contribute 23.0% (17.9-30.5) of new HCV infections. If prison-based interventions had not been implemented since 2010, HCV incidence in 2020 would have been 29.7% (95% credibility interval: 22.4-36.1) higher. If current prison and community HCV treatment rates continue, there is an 98.8% probability that elimination targets will be achieved by 2030, with this decreasing to 10.1% without current prison-based interventions. CONCLUSIONS: Existing prison-based interventions in NSW are critical components of strategies to reduce HCV incidence among PWID. Prison-based interventions are likely to be pivotal for achieving HCV elimination targets among PWID by 2030.

Modeling the impact of interventions during an outbreak of HIV infection among people who inject drugs in 2012-2013 in Athens, Greece.

BACKGROUND: A large HIV outbreak in People Who Inject Drugs (PWID) occurred in Athens, Greece in 2011-2013. In response, opioid substitution treatment (OST) and needle and syringe programs (NSP) were scaled-up and a seek-test-treat program was introduced in mid-2012. We aim to assess the impact of these interventions. METHODS: A mathematical model of HIV transmission among PWID was calibrated to data available over time (2009-2013) on HIV prevalence, NSP/antiretroviral treatment (ART) coverage and high-risk injection. A combined interventions scenario, including decrease in high-risk injection through linkage to OST and modification of risk behaviours and access to NSP and ART, was compared to a counterfactual scenario (no improvement at the levels of these interventions), with HIV incidence being the main outcome. RESULTS: HIV incidence increased from <0.1 new cases/100 person-years (in 2009) to 11.0 new cases/100 person-years (in 2012). Under both models, a subsequent decline was projected following early 2012, with incidence at the end of 2013 in the combined interventions scenario being lower by 77% compared to the counterfactual. The projected reduction in incidence under the intervention scenario was in agreement with empirical data. HIV prevalence would have escalated to 20.4% (95% CrI: 16.9%, 23.6%) in 2013 under the counterfactual scenario (vs. 16.8% (95% CrI: 11.2%, 23.0%) under the combined interventions scenario). In total, 31.4% of HIV cases (392) were averted over 2012-2013. CONCLUSION: These results underline the importance of high-coverage harm reduction programs and of community-based interventions to rapidly reach PWID most in need.

Methods and indicators to validate country reductions in incidence of hepatitis C virus infection to elimination levels set by WHO.

One of the main goals of the 2016 Global Health Sector Strategy on viral hepatitis is the elimination of hepatitis C virus (HCV) as a public health problem by 2030, defined as an 80% reduction in incidence and 65% reduction in mortality relative to 2015. Although monitoring HCV incidence is key to validating HCV elimination, use of the gold-standard method, which involves prospective HCV retesting of people at risk, can be prohibitively resource-intensive. Additionally, few countries collected quality data in 2015 to enable an 80% decrease by 2030 to be calculated. Here, we first review different methods of monitoring HCV incidence and discuss their resource implications and applicability to various populations. Second, using mathematical models developed for various global settings, we assess whether trends in HCV chronic prevalence or HCV antibody prevalence or scale-up levels for HCV testing, treatment, and preventative interventions can be used as reliable alternative indicators to validate the HCV incidence target. Third, we discuss the advantages and disadvantages of an absolute HCV incidence target and suggest a suitable threshold. Finally, we propose three options that countries can use to validate the HCV incidence target, depending on the available surveillance infrastructure.

Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis.

BACKGROUND: Modelling suggests that achieving the WHO incidence target for hepatitis C virus (HCV) elimination in Pakistan could cost US$3.87 billion over 2018 to 2030. However, the economic benefits from integrating services or improving productivity were not included. METHODS AND FINDINGS: We adapt a HCV transmission model for Pakistan to estimate the impact, costs, and cost-effectiveness of achieving HCV elimination (reducing annual HCV incidence by 80% by 2030) with stand-alone service delivery, or partially integrating one-third of initial HCV testing into existing healthcare services. We estimate the net economic benefits by comparing the required investment in screening, treatment, and healthcare management to the economic productivity gains from reduced HCV-attributable absenteeism, presenteeism, and premature deaths. We also calculate the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for HCV elimination versus maintaining current levels of HCV treatment. This is compared to an opportunity cost-based willingness-to-pay threshold for Pakistan (US$148 to US$198/DALY). Compared to existing levels of treatment, scaling up screening and treatment to achieve HCV elimination in Pakistan averts 5.57 (95% uncertainty interval (UI) 3.80 to 8.22) million DALYs and 333,000 (219,000 to 509,000) HCV-related deaths over 2018 to 2030. If HCV testing is partially integrated, this scale-up requires an investment of US$1.45 (1.32 to 1.60) billion but will result in US$1.30 (0.94 to 1.72) billion in improved economic productivity over 2018 to 2030. This elimination strategy is highly cost-effective (ICER = US$29 per DALY averted) by 2030, with it becoming cost-saving by 2031 and having a net economic benefit of US$9.10 (95% UI 6.54 to 11.99) billion by 2050. Limitations include uncertainty around what level of integration is possible within existing primary healthcare services as well as a lack of Pakistan-specific data on disease-related healthcare management costs or productivity losses due to HCV. CONCLUSIONS: Investment in HCV elimination can bring about substantial societal health and economic benefits for Pakistan.

Elucidating Drivers for Variations in the Explosive Human Immunodeficiency Virus Epidemic Among People Who Inject Drugs in Pakistan.

BACKGROUND: Pakistan's explosive human immunodeficiency virus (HIV) epidemic among people who inject drugs (PWID) varies widely across cities. We evaluated possible drivers for these variations. METHODS: Multivariable regression analyses were undertaken using data from 5 national surveys among PWID (n = 18 467; 2005-2017) to determine risk factors associated with variations in city-level HIV prevalence. A dynamic HIV model was used to estimate the population-attributable fraction (PAF; proportion of HIV infections prevented over 10 years when that risk factor is removed) of these risk factors to HIV transmission and impact on HIV incidence of reducing their prevalence. RESULTS: Regression analyses suggested that city-level HIV prevalence is strongly associated with the prevalence of using professional injectors at last injection, heroin use in last month, and injecting ≥4 times per day. Through calibrating a model to these associations, we estimate that the 10-year PAFs of using professional injectors, heroin use, and frequent injecting are 45.3% (95% uncertainty interval [UI], 4.3%-79.7%), 45.9% (95% UI, 8.1%-78.4%), and 22.2% (95% UI, 2.0%-58.4%), respectively. Reducing to lowest city-level prevalences of using professional injectors (2.8%; median 89.9% reduction), heroin use (0.9%; median 91.2% reduction), and frequent injecting (0.1%; median 91.8% reduction) in 2020 reduces overall HIV incidence by 52.7% (95% UI, 6.1%-82.0%), 53.0% (95% UI, 11.3%-80.2%), and 28.1% (95% UI, 2.7%-66.6%), respectively, over 10 years. CONCLUSIONS: Interventions should focus on these risk factors to control Pakistan's explosive HIV epidemic among PWID, including a concomitant expansion of high-coverage needle/syringe provision, opioid substitution therapy, and antiretroviral therapy.

Evaluating the Prevention Benefit of HCV Treatment: Modeling the SToP-C Treatment as Prevention Study in Prisons.

BACKGROUND AND AIMS: Between 2014 and 2019, the SToP-C trial observed a halving in HCV incidence in four Australian prisons following scale-up of direct-acting antiviral (DAA) therapy. However, the contribution of HCV treatment to this decline is unclear because the study did not have a control group. We used modeling to consider this question. APPROACH AND RESULTS: We parameterized and calibrated a dynamic model of HCV transmission in prisons to data from each SToP-C prison on incarceration dynamics, injecting drug use, HCV prevalence trends among prison entrants, baseline HCV incidence before treatment scale-up, and subsequent HCV treatment scale-up. The model projected the decrease in HCV incidence resulting from increases in HCV treatment and other effects. We assessed whether the model agreed better with observed reductions in HCV incidence overall and by prison if we included HCV treatment scale-up, and its prevention benefits, or did not. The model estimated how much of the observed decrease in HCV incidence was attributable to HCV treatment in prison. The model projected a decrease in HCV incidence of 48.5% (95% uncertainty interval [UI], 41.9-54.1) following treatment scale-up across the four prisons, agreeing with the observed HCV incidence decrease (47.6%; 95% CI, 23.4-64.2) from the SToP-C trial. Without any in-prison HCV treatment, the model indicated that incidence would have decreased by 7.2% (95% UI, -0.3 to 13.6). This suggests that 85.1% (95% UI, 72.6-100.6) of the observed halving in incidence was from HCV treatment scale-up, with the remainder from observed decreases in HCV prevalence among prison entrants (14.9%; 95% UI, -0.6 to 27.4). CONCLUSIONS: Our results demonstrate the prevention benefits of scaling up HCV treatment in prison settings. Prison-based DAA scale-up should be an important component of HCV elimination strategies.

Impact of screening on the prevalence and incidence of Mycoplasma genitalium and its macrolide resistance in men who have sex with men living in Australia: A mathematical model.

BACKGROUND: Mycoplasma genitalium (MG) causes a sexually transmitted infection (STI) with a rising rate of antimicrobial resistance. Currently, guidelines do not recommend screening asymptomatic men who have sex with men (MSM). We developed a mathematical model of MG transmission to examine the impact of various screening strategies on the incidence and prevalence of MG among MSM attending a sexual health clinic. METHODS: A compartmental mathematical model of MG transmission among MSM was constructed and calibrated using data from the Melbourne Sexual Health center, where resistance-guided therapy provides high treatment effectiveness (92-95%). The model stratified men by symptom status, sexual risk behaviours and whether or not they had MG with macrolide resistance. We simulated the impact on endemic steady-state MG prevalence and incidence of the following screening scenarios, namely screening: 1) no MSM; 2) only symptomatic MSM (the current recommendation); 3) all symptomatic and high-risk asymptomatic MSM; and 4) all MSM. Our base case analysis assumed a treatment effectiveness of 92-95% using resistance-guided therapy. We also examined the impact of treatment effectiveness (i.e. the proportion of detected MG that were cured) and screening coverage (i.e. testing rate) on MG prevalence. FINDINGS: The model predicts that the overall endemic MG prevalence is 9.1% (95% CI: 7.9-10.0) in the current situation where screening is only offered to symptomatic MSM (base-case). This would increase to 11·4% (95% confidence intervals (CI): 10.2-13.7) if no MSM are offered screening, but would decrease to 7.3% (95% CI: 5.7-8.4) if all symptomatic and high-risk asymptomatic MSM were offered screening and 6.4% (95% CI: 4.7-7·7) if all MSM were offered screening. Increasing coverage of MSM screening strategies shows a similar effect on decreasing endemic MG incidence. When evaluating the simultaneous impact of treatment effectiveness and screening coverage, we found that offering screening to more MSM may reduce the overall prevalence but leads to a higher proportion of macrolide-resistant MG, particularly when using treatment regimens with lower effectiveness. INTERPRETATION: Based on the available treatment options, offering screening for MG to other MSM (beyond the currently recommended group of symptomatic MSM) could slightly reduce the prevalence and incidence of MG. However, further increasing screening coverage must be weighed against the impact of lower treatment effectiveness (i.e. when not using resistance-guided therapy), increasing the selection of macrolide resistance, and other negative consequences related to AMR and management (e.g. unnecessary psychological morbidity from infections that do not need treatment).

Homelessness, unstable housing, and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis.

BACKGROUND: People who inject drugs (PWID) are at increased risk for HIV and hepatitis C virus (HCV) infection and also have high levels of homelessness and unstable housing. We assessed whether homelessness or unstable housing is associated with an increased risk of HIV or HCV acquisition among PWID compared with PWID who are not homeless or are stably housed. METHODS: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies published between Jan 1, 2000, and June 13, 2017. Using the same strategy as for this existing database, we searched MEDLINE, Embase, and PsycINFO for studies, including conference abstracts, published between June 13, 2017, and Sept 14, 2020, that estimated HIV or HCV incidence, or both, among community-recruited PWID. We only included studies reporting original results without restrictions to study design or language. We contacted authors of studies that reported HIV or HCV incidence, or both, but did not report on an association with homelessness or unstable housing, to request crude data and, where possible, adjusted effect estimates. We extracted effect estimates and pooled data using random-effects meta-analyses to quantify the associations between recent (current or within the past year) homelessness or unstable housing compared with not recent homelessness or unstable housing, and risk of HIV or HCV acquisition. We assessed risk of bias using the Newcastle-Ottawa Scale and between-study heterogeneity using the I2 statistic and p value for heterogeneity. FINDINGS: We identified 14 351 references in our database search, of which 392 were subjected to full-text review alongside 277 studies from our existing database. Of these studies, 55 studies met inclusion criteria. We contacted the authors of 227 studies that reported HIV or HCV incidence in PWID but did not report association with the exposure of interest and obtained 48 unpublished estimates from 21 studies. After removal of duplicate data, we included 37 studies with 70 estimates (26 for HIV; 44 for HCV). Studies originated from 16 countries including in North America, Europe, Australia, east Africa, and Asia. Pooling unadjusted estimates, recent homelessness or unstable housing was associated with an increased risk of acquiring HIV (crude relative risk [cRR] 1·55 [95% CI 1·23-1·95; p=0·0002]; I2= 62·7%; n=17) and HCV (1·65 [1·44-1·90; p<0·0001]; I2= 44·8%; n=28]) among PWID compared with those who were not homeless or were stably housed. Associations for both HIV and HCV persisted when pooling adjusted estimates (adjusted relative risk for HIV: 1·39 [95% CI 1·06-1·84; p=0·019]; I2= 65·5%; n=9; and for HCV: 1·64 [1·43-1·89; p<0·0001]; I2= 9·6%; n=14). For risk of HIV acquisition, the association for unstable housing (cRR 1·82 [1·13-2·95; p=0·014]; n=5) was higher than for homelessness (1·44 [1·13-1·83; p=0·0036]; n=12), whereas no difference was seen between these outcomes for risk of HCV acquisition (1·72 [1·48-1·99; p<0·0001] for unstable housing, 1·66 [1·37-2·00; p<0·0001] for homelessness). INTERPRETATION: Homelessness and unstable housing are associated with increased risk of HIV and HCV acquisition among PWID. Our findings support the development of interventions that simultaneously address homelessness and unstable housing and HIV and HCV transmission in this population. FUNDING: National Institute for Health Research, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, and Commonwealth Scholarship Commission.

Cost-effectiveness of screening and treatment using direct-acting antivirals for chronic Hepatitis C virus in a primary care setting in Karachi, Pakistan.

Despite the availability of effective direct-acting antiviral (DAA) treatments for Hepatitis C virus (HCV) infection, many people remain undiagnosed and untreated. We assessed the cost-effectiveness of a Médecins Sans Frontières (MSF) HCV screening and treatment programme within a primary health clinic in Karachi, Pakistan. A health state transition Markov model was developed to estimate the cost-effectiveness of the MSF programme. Programme cost and outcome data were analysed retrospectively. The incremental cost-effectiveness ratio (ICER) was calculated in terms of incremental cost (2016 US$) per disability-adjusted life year (DALY) averted from the provider's perspective over a lifetime horizon. The robustness of the model was evaluated using deterministic and probabilistic sensitivity analyses (PSA). The ICER for implementing testing and treatment compared to no programme was US$450/DALY averted, with 100% of PSA runs falling below the per capita Gross Domestic Product threshold for cost-effective interventions for Pakistan (US$1,422). The ICER increased to US$532/DALY averted assuming national HCV seroprevalence (5.5% versus 33% observed in the intervention). If the cost of liver disease care was included (adapted from resource use data from Cambodia which has similar GDP to Pakistan), the ICER dropped to US$148/DALY, while it became cost-saving if a recently negotiated reduced drug cost of $75/treatment course was assumed (versus $282 in base-case) in addition to cost of liver disease care. In conclusion, screening and DAA treatment for HCV infection are expected to be highly cost-effective in Pakistan, supporting the expansion of similar screening and treatment programmes across Pakistan.

Health-related quality of life of long-term patients receiving opioid agonist therapy: a nested prospective cohort study in Norway.

BACKGROUND: Opioid dependence carries the highest disease burden of all illicit drugs. Opioid agonist therapy (OAT) is an evidence-based medical intervention that reduces morbidity and mortality. There is limited knowledge on the health-related quality of life (HRQoL) of long-term patients in OAT. This study measures HRQoL and self-perceived health of long-term patients on OAT, compares the scores to a Norwegian reference population, and assesses changes in these scores at 1-year follow up. METHODS: We conducted a nested prospective cohort study among nine OAT outpatient clinics in Norway. 609 OAT patients were included, 245 (40%) followed-up one year later. Data on patient characteristics, HRQoL, and self-perceived health was collected. HRQoL was assessed with the EQ-5D-5L, which measures five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) on a five-point Likert scale (from "no problems" to "extreme problems"). An UK value set was applied to calculate index values (from 0 to 1) for the EQ-5D-5L and compare them to a Norwegian reference population. Self-perceived health was measured with EQ-VAS (from 0 to 100). RESULTS: Mean (standard deviation (SD)) EQ-5D-5L index value at baseline was 0.699 (0.250) and EQ-VAS 57 (22) compared to 0.848 (0.200) and 80(19) for the Norwegian reference population. There were large variations in EQ-5D-5L index values, where 43% had > 0.8 and 5% had < 0.2 at baseline. The lowest EQ-5D-5L index values were observed for female patients, age groups older than 40 years and for methadone users. At follow-up, improvements in HRQoL were observed across almost all dimensions and found significant for mobility and pain/discomfort. Mean (SD) overall index value and EQ-VAS at follow up were 0.729 (0.237) and 59 (22) respectively. CONCLUSION: The average HRQoL and self-perceived health of OAT patients is significantly lower than that of the general population, and lower than what has been found among other severe somatic and psychiatric conditions. Around 34% had very good HRQoL, higher than average Norwegian values, and around 5% had extremely poor HRQoL.

Has resourcing of non-governmental harm-reduction organizations in Ukraine improved HIV prevention and treatment outcomes for people who inject drugs? Findings from multiple bio-behavioural surveys.

INTRODUCTION: People who inject drugs (PWID) in Ukraine have high prevalences of HIV and hepatitis C (HCV). Since the turn of the century, various organizations have funded non-governmental organizations (NGOs) in Ukraine to provide PWID with needles and syringes, condoms, HIV and HCV testing, and improve linkage to opioid agonist therapy (OAT) and HIV treatment. We investigated whether contact with these NGOs was associated with improved HIV prevention and treatment outcomes among PWID. METHODS: Five rounds of respondent-driven sampled integrated bio-behavioural survey data (2009 [N = 3962], 2011 [N = 9069], 2013 [N = 9502], 2015 [N = 9405], and 2017 [N = 10076]) among PWID in Ukraine (including HIV/HCV testing and questionnaires) were analysed using mixed-effect logistic regression models (mixed-effects: city, year). These regression models assessed associations between being an NGO client and various behavioural, OAT, HIV testing and HIV treatment outcomes, adjusting for demographic characteristics (age, gender, lifetime imprisonment, registration in a drug abuse clinic, education level). We also assessed associations between being an NGO client and being HIV positive or HCV positive, likewise adjusting for demographic characteristics (as above). RESULTS: NGO clients were more likely to have received HIV testing ever (adjusted odds ratio [aOR] 5.37, 95% confidence interval [95% CI]: 4.97 to 5.80) or in the last year (aOR 3.37, 95% CI: 3.20 to 3.54), to have used condoms at last sexual intercourse (aOR 1.37, 95% CI: 1.30 to 1.44) and sterile needles at last injection (aOR 1.37, 95% CI: 1.20 to 1.56), to be currently (aOR 4.19, 95% CI: 3.48 to 5.05) or ever (aOR 2.52, 95% CI: 2.32 to 2.74) on OAT, and to have received syringes (aOR 109.89, 95% CI: 99.26 to 121.66) or condoms (aOR 54.39, 95% CI: 50.17 to 58.96) in the last year. PWID who were HIV positive (aOR 1.40, 95% CI: 1.33 to 1.48) or HCV positive (aOR 1.57, 95% CI: 1.49 to 1.65) were more likely to have contact with NGOs, with HIV positive PWID in contact with NGOs being more likely to be registered at AIDS centres (aOR 2.34, 95% CI: 1.88 to 2.92) and to be on antiretroviral therapy (aOR 1.60, 95% CI: 1.40 to 1.83). CONCLUSIONS: Contact with PWID targeted NGOs in Ukraine is associated with consistently better preventive, HIV testing and HIV treatment outcomes, suggesting a beneficial impact of harm reduction NGO programming.

Uptake and predictors of direct-acting antiviral treatment for hepatitis C among people receiving opioid agonist therapy in Sweden and Norway: a drug utilization study from 2014 to 2017.

BACKGROUND: Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries. METHODS: This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. HCV prevalence was estimated from primary and secondary sources. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were conditionally adjusted for age, gender, and OAT medications. Logistic regression was used to evaluate these parameters. RESULTS: In total 3529 individuals were identified with dispensed OAT in the Swedish cohort and 7739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV and DAA treatment uptake increased in both countries. The estimated cumulative HCV treatment uptake at the end of 2017 was 31% in Norway and 28% in Sweden. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0-3.2) and the dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8-5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2-0.9, aOR 0.8; 95%CI 0.6-1.0). CONCLUSIONS: An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients whilst introducing new direct-acting antiviral treatment regimens. However, more than two thirds of the OAT population in Norway and Sweden were untreated at the beginning of 2018. A further scale-up is crucial in order to control and eliminate the HCV endemic among OAT patients.

Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis.

BACKGROUND: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. METHODS: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. FINDINGS: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13·8 million (95% UI 13·4-14·1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26·5% (22·5-30·7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46·8% and decrease incidence by 50·8% (95% UI 46·1-55·0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to $3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. INTERPRETATION: Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. FUNDING: UNITAID.

Interim effect evaluation of the hepatitis C elimination programme in Georgia: a modelling study.

BACKGROUND: Georgia has a high prevalence of hepatitis C, with 5·4% of adults chronically infected. On April 28, 2015, Georgia launched a national programme to eliminate hepatitis C by 2020 (90% reduction in prevalence) through scaled-up treatment and prevention interventions. We evaluated the interim effect of the programme and feasibility of achieving the elimination goal. METHODS: We developed a transmission model to capture the hepatitis C epidemic in Georgia, calibrated to data from biobehavioural surveys of people who inject drugs (PWID; 1998-2015) and a national survey (2015). We projected the effect of the administration of direct-acting antiviral treatments until Feb 28, 2019, and the effect of continuing current treatment rates until the end of 2020. Effect was estimated in terms of the relative decrease in hepatitis C incidence, prevalence, and mortality relative to 2015 and of the deaths and infections averted compared with a counterfactual of no treatment over the study period. We also estimated treatment rates needed to reach Georgia's elimination target. FINDINGS: From May 1, 2015, to Feb 28, 2019, 54 313 patients were treated, with approximately 1000 patients treated per month since mid 2017. Compared with 2015, our model projects that these treatments have reduced the prevalence of adult chronic hepatitis C by a median 37% (95% credible interval 30-44), the incidence of chronic hepatitis C by 37% (29-44), and chronic hepatitis C mortality by 14% (3-30) and have prevented 3516 (1842-6250) new infections and averted 252 (134-389) deaths related to chronic hepatitis C. Continuing treatment of 1000 patients per month is predicted to reduce prevalence by 51% (42-61) and incidence by 51% (40-62), by the end of 2020. To reach a 90% reduction by 2020, treatment rates must increase to 4144 (2963-5322) patients initiating treatment per month. INTERPRETATION: Georgia's hepatitis C elimination programme has achieved substantial treatment scale-up, which has reduced the burden of chronic hepatitis C. However, the country is unlikely to meet its 2020 elimination target unless treatment scales up considerably. FUNDING: CDC Foundation, National Institute for Health Research, National Institutes of Health.