Impact of HCV Testing and Treatment on HCV Transmission Among Men Who Have Sex With Men and Who Inject Drugs in San Francisco: A Modelling Analysis.

BACKGROUND: Men who have sex with men who ever injected drugs (ever MSM-IDU) carry a high hepatitis C virus (HCV) burden. We estimated whether current HCV testing and treatment in San Francisco can achieve the 2030 World Health Organization (WHO) HCV elimination target on HCV incidence among ever MSM-IDU. METHODS: A dynamic HCV/HIV transmission model among MSM was calibrated to San Francisco data, including HCV antibody (15.5%, 2011) and HIV prevalence (32.8%, 2017) among ever MSM-IDU. MSM had high HCV testing (79%-86% ever tested, 2011-2019) and diagnosed MSM had high HCV treatment (65% ever treated, 2018). Following coronavirus disease 2019 (COVID-19)-related lockdowns, HCV testing and treatment decreased by 59%. RESULTS: Among all MSM, 43% of incident HCV infections in 2022 were IDU-related. Among ever MSM-IDU in 2015, HCV incidence was 1.2/100 person-years (95% credibility interval [CrI], 0.8-1.6). Assuming COVID-19-related declines in HCV testing/treatment persist until 2030, HCV incidence among ever MSM-IDU will decrease by 84.9% (95% CrI, 72.3%-90.8%) over 2015-2030. This decline is largely attributed to HCV testing and treatment (75.8%; 95% CrI, 66.7%-89.5%). Slightly greater decreases in HCV incidence (94%-95%) are projected if COVID-19 disruptions recover by 2025 or 2022. CONCLUSIONS: We estimate that HCV incidence will decline by >80% over 2015-2030 among ever MSM-IDU in San Francisco, achieving the WHO target.

Patient-Reported Outcomes During and After Hepatitis C Virus Direct-Acting Antiviral Treatment Among People Who Inject Drugs.

OBJECTIVES: People who inject drugs (PWID) are at a high risk of hepatitis C virus (HCV) infection. HCV cure is associated with improved patient-reported outcomes (PROs), but there are little data among PWID. This study aimed to assess the change in PROs during and after HCV direct-acting antiviral (DAA) treatment. METHODS: This analysis used data from 2 clinical trials of DAA treatment in PWID. PROs assessed included health-related quality of life, social functioning, psychological distress, housing, and employment. Generalized estimating equations and group-based trajectory modeling were used to assess changes in PROs over time. RESULTS: No significant changes in the 3-level version of EQ-5D scores, EQ visual analogue scale scores, social functioning, psychological distress, and housing were observed over the 108-week study period. There was a significant increase in the proportion of participants employed (18% [95% confidence interval (CI) 12%-23%] at baseline to 28% [95% CI 19%-36%] at the end of the study). Participants were more likely to be employed at 24 weeks and 108 weeks after commencing treatment. Having stable housing increased the odds of being employed (odds ratio 1.70; 95% CI 1.00-2.90). The group-based trajectory modeling demonstrated that most outcomes remained stable during and after DAA treatment. CONCLUSIONS: Although no significant improvement was identified in health-related quality of life after HCV DAA treatment, there was a modest but significant increase in employment during study follow-up. The study findings support the need for multifaceted models of HCV care for PWID addressing a range of issues beyond HCV treatment to improve quality of life.

Association between binge drug use and suicide attempt among people who inject drugs.

BACKGROUND: People who inject drugs (PWID) have an elevated risk of suicide attempt. Although different substances are associated with suicide attempt, the overall risk posed by binge behavior, a high-risk pattern of drug use, remains unclear. The objective of this study is to assess the association between binge drug use and suicide attempt in a prospective cohort of PWID in Montreal, Canada. METHODS: Participants answered a biannual interviewer-administered questionnaire compiling information on sociodemographics, pattern of substance use (cocaine, amphetamine, opioids, sedative-hypnotics, alcohol, and cannabis), and psychosocial stressors and related markers. The relationship between suicide attempt and binge behavior was modeled using generalized estimating equations (GEEs), controlling for type and pattern of substance use, sociodemographic characteristics, and significant mental health markers. RESULTS: Among 1240 participants (mean age ± SD: 38.2 ± 9.8) at baseline, 222 (17.9%) reported binge during the past 6-months. PWID reporting binge were significantly younger (P < .001), less educated (P = .012), less likely male (P = .047), and had shorter history of injection (P < .001). In addition, they were younger at first injection (P = .014), reported higher rates of prostitution and psychological disorders (P = .003), and were more likely to use other drugs except cannabis and alcohol. Binge was independently associated with attempted suicide in the GEE multivariate model (adjusted odds ratio [aOR 95% CI] = 1.91 [1.38-2.65], P < .001). CONCLUSIONS: Among PWID at high risk of suicide attempt, those who binge represent a particularly vulnerable subgroup. Although the exact mechanisms underlying this finding remain unresolved, several hypothesis pertaining to the neurobiological and psychosocial consequences of binge, as well as common personality traits, warrant further investigations.

Modeling the impact of the COVID-19 pandemic on achieving HCV elimination amongst young and unstably housed people who inject drugs in San Francisco.

BACKGROUND: Young adult (18-30 years) people who inject drugs (PWID) face high hepatitis C virus (HCV) prevalence. In San Francisco, where >60% of PWID lack stable housing, barriers hinder HCV treatment access. We assessed progress towards the World Health Organization's (WHO) HCV elimination goal of an 80% reduction in incidence over 2015-2030, focusing on young (YPWID) and unstably housed PWID in San Francisco. METHODS: We developed a dynamic HCV transmission model among PWID, parameterized and calibrated using bio-behavioural survey datasets from San Francisco. This included 2018 estimates for the antibody-prevalence among PWID (77%) and care cascade estimates for HCV for YPWID (72% aware of their status and 33% ever initiating treatment). Based on programmatic data, we assumed a 53.8% reduction in testing and 40.7% decrease in treatment from 2020 due to the COVID-19 pandemic, which partially rebounded from April 2021 with testing rates then being 31.1% lower than pre-pandemic rates and treatment numbers being 19.5% lower. We simulated different scenarios of how services changed after the pandemic to project whether elimination goals would be met. RESULTS: Continuing post-pandemic rates of testing and treatment, the model projects an 83.3% (95% credibility interval [95% CrI]:60.6-96.9%) decrease in incidence among PWID over 2015-2030 to 1.5/100pyrs (95% CrI:0.3-4.4) in 2030. The probability of achieving the elimination goal by 2030 is 62.0%. Among YPWID and unstably housed PWID, the probability of achieving the elimination goal by 2030 is 54.8 and 67.6%, respectively. Importantly, further increasing testing and treatment rates to pre-pandemic levels by 2025 only results in a small increase in the probability (67.5%) of the elimination goal being achieved among all PWID by 2030, while increased coverage of medication for opioid use disorder among YPWID and/or housing interventions results in the probability of achieving elimination increasing to over 75%. CONCLUSION: The COVID-19 pandemic impeded progress toward achieving HCV elimination. Our findings indicate that existing partial rebounds in HCV testing and treatment may achieve the elimination goal by 2030, with an additional scale-up of interventions aimed at YPWID or unstably housed PWID ensuring San Francisco is likely to achieve elimination by 2030.

Sex and gender differences in hepatitis C virus risk, prevention, and cascade of care in people who inject drugs: systematic review and meta-analysis.

Background: People who inject drugs (PWID) are a priority population in HCV elimination programming. Overcoming sex and gender disparities in HCV risk, prevention, and the cascade of care is likely to be important to achieving this goal, but these have not yet been comprehensively reviewed. Methods: Systematic review and meta-analysis. We searched Pubmed, EMBASE and the Cochrane Database of Systematic Reviews 1 January 2012-22 January 2024 for studies of any design reporting sex or gender differences among PWID in at least one of: sharing of needles and/or syringes, incarceration history, injection while incarcerated, participation in opioid agonist treatment or needle and syringe programs, HCV testing, spontaneous HCV clearance, direct-acting antiviral (DAA) treatment initiation or completion, and sustained virological response (SVR). Assessment of study quality was based on selected aspects of study design. Additional data were requested from study authors. Data were extracted in duplicate and meta-analysed using random effects models. PROSPERO registration CRD42022342806. Findings: 9533 studies were identified and 92 studies were included. Compared to men, women were at greater risk for receptive needle and syringe sharing (past 6-12 months: risk ratio (RR) 1.12; 95% confidence interval (CI) 1.01-1.23; <6 months: RR 1.38; 95% CI 1.09-1.76), less likely to be incarcerated (lifetime RR 0.64; 95% CI 0.57-0.73) more likely to be tested for HCV infection (lifetime RR 1.07; 95% CI 1.01, 1.14), more likely to spontaneously clear infection (RR1.58; 95% CI 1.40-1.79), less likely to initiate DAA treatment (0.84; 95% CI 0.78-0.90), and more likely to attain SVR after completing DAA treatment (RR 1.02; 95% CI 1.01-1.04). Interpretation: There are important differences in HCV risk and cascade of care indicators among people who inject drugs that may impact the effectiveness of prevention and treatment programming. Developing and assessing the effectiveness of gender-specific and gender-responsive HCV interventions should be a priority in elimination programming. Funding: Réseau SIDA-MI du Québec.

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.

The contribution of unstable housing to HIV and hepatitis C virus transmission among people who inject drugs globally, regionally, and at country level: a modelling study.

BACKGROUND: A considerable proportion of people who inject drugs are unstably housed. Although unstable housing is associated with HIV and HCV infection among people who inject drugs, its contribution to transmission is unknown. We estimated the global and national proportions of incident HIV and HCV infections among people who inject drugs attributed to housing instability from 2020 to 2029. METHODS: In this modelling study, we developed country-level models of unstable housing and HIV and HCV transmission among people who inject drugs in 58 countries globally, calibrated to country-specific data on the prevalences of HIV and HCV and unstable housing. Based on a recently published systematic review, unstably housed people who inject drugs were assumed to have a 39% (95% CI 6-84) increased risk of HIV transmission and a 64% (95% CI 43-89%) increased risk of HCV transmission. We used pooled country-level estimates from systematic reviews on HCV and HIV prevalence in people who inject drugs. Our models estimated the transmission population attributable fraction (tPAF) of unstable housing to HIV and HCV transmission among people who inject drugs, defined as the percentage of infections prevented from 2020 to 2029 if the additional risk due to unstable housing was removed. FINDINGS: Our models were produced for 58 countries with sufficient data (accounting for >66% of the global people who inject drugs population). Globally, we project unstable housing contributes 7·9% (95% credibility interval [CrI] 2·3-15·7) of new HIV infections and 11·2% (7·7-15·5) of new HCV infections among people who inject drugs from 2020 to 2029. Country-level tPAFs were strongly associated with the prevalence of unstable housing. tPAFs were greater in high-income countries (HIV 17·2% [95% CrI 5·1-30·0]; HCV 19·4% [95% CrI 13·8-26·0]) than in low-income or middle-income countries (HIV 6·6% [95% CrI 1·8-13·1]; HCV 8·3% [95% CrI 5·5-11·7]). tPAFs for HIV and HCV were highest in Afghanistan, Czech Republic, India, USA, England, and Wales where unstable housing contributed more than 20% of new HIV and HCV infections. INTERPRETATION: Unstable housing is an important modifiable risk factor for HIV and HCV transmission among people who inject drugs in many countries. The study emphasises the importance of implementing initiatives to mitigate these risks and reduce housing instability. FUNDING: National Institute for Health Research and National Institute of Allergy and Infectious Diseases and National Institute for Drug Abuse.

Perceived availability and carriage of take-home naloxone and factors associated with carriage among people who inject drugs in England, Wales and Northern Ireland.

BACKGROUND: In 2019-2020, record-high numbers of overdoses have been reported across the UK. We estimated perceived availability to and carriage of naloxone and explored factors associated with carriage among people who inject drugs (PWID) engaged with services in England, Wales, and Northern Ireland. METHODS: Participants were PWID enrolled in the Unlinked Anonymous Monitoring Survey in 2019 who reported past-year injection drug use (n = 2,139). Recruitment occurred through specialist and community drug agencies located across the UK, excluding Scotland. Socio-demographic, behavioural and service use characteristics were self-reported. Participants were asked whether they carry naloxone (timeframe unspecified). If they answered "no", they were further asked whether it is available in their area. Perceived naloxone availability and carriage were estimated by requirement region, classified using the Nomenclature of Territorial Units for Statistics 1. We used the Gelberg-Andersen Model of healthcare access to explore predisposing, enabling and need factors associated with regionally-aggregated naloxone carriage. RESULTS: Perceived naloxone availability was ≥95% in all 11 regions; naloxone carriage varied (mean: 61.1; range: 48%-71%; P<0.01). Among predisposing factors, female gender (adjusted odds ratio (AOR): 1.52; 95% confidence interval (CI): 1.21-1.91) was positively associated with naloxone carriage, whilst recruitment in Yorkshire and the Humber-relative to London-was negatively associated (AOR: 0.55; 95%CI: 0.37-0.82). Among enabling factors, past-year contact with needle and syringe programmes (AOR: 1.74; 95%CI: 1.39-2.18) and currently receiving treatment for drug use (AOR: 1.75; 95%CI: 1.24-2.46) were positively associated with naloxone carriage. Among need characteristics, past-month heroin injection, with or without past-month high-risk drinking or benzodiazepine use, was positively associated with carriage relative to no heroin injection (range of AORs: 1.71-2.58). CONCLUSION: Perceived naloxone availability is very high among PWID attending services in England, Wales, and Northern Ireland. Naloxone carriage is moderately high and varying across regions, and appears improved through recent engagement with harm-reduction programs.

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.

Transitioning from interferon-based to direct antiviral treatment options: A potential shift in barriers and facilitators of treatment initiation among people who use drugs?

BACKGROUND: Multiple barriers for accessing hepatitis C virus (HCV) treatment were identified during the interferon-based (IFN) treatment era for people who inject drugs (PWID). Whether these barriers persist since the introduction of IFN-free direct-acting antiviral (DAA) agents in Canada remains to be documented. This study examined temporal trends in HCV treatment initiation and associated factors during the transition from INF-based to all-oral DAA regimens. METHODS: The study population was drawn from a prospective cohort of PWID in Montreal, Canada. At three-month/one-year intervals between 2011 and 2017, participants with chronic HCV infection completed an interviewer-administered questionnaire on socio-demographic characteristics, drug use and health service utilisation, including HCV treatment. Time-updated Cox multivariate regression models, stratified by DAA + INF (2011-2013) and all-oral DAA (2014-2017) availability periods, were conducted to examine associations between time to HCV treatment initiation and associated barriers and facilitators. RESULTS: Of 308 participants (85% male, median age 42 [IQR: 33, 50]), 80 (26%) initiated HCV treatment during 915 person-years (PY). Incidence rates increased from 1.6 /100 PY (95%CI:0.9-2.6) in 2011 to 12.7 (10.6-15.1) in 2017 (p-trend = 0.0012). In multivariate analyses, visiting a primary care physician (2011-2013: aHR = 3.63[1.21-10.9]; 2014-2017: 2.52[1.10-5.77]) and frequent injection (0.23[0.05-0.99] and 0.49[0.24-0.99]) were consistently associated with treatment initiation. Participants aged >40 (2.27[1.24-4.13]), receiving opioid agonist therapy (OAT) (2.17[1.19-3.94]), and reporting prior HCV treatment (3.00[1.75-5.15]) were more likely to initiate treatment in the all-oral DAA period. CONCLUSION: Treatment initiation increased between 2011 and 2017, but still remains low among PWID. Primary care visiting was a key facilitator regardless of the period, while engagement in OAT and health services, indicated by prior HCV treatment, increased the likelihood of treatment initiation in the DAA era. These findings suggest that access to health services is essential but not enough to scale up treatment in this population.