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People who use injection drugs (PWID) experience high rates of HIV acquisition and, as a result of lower rates of optimal access and adherence to combination antiretroviral therapy (ART), experience worse HIV treatment outcomes than other key affected populations. However, the incidence and risk factors for the development of AIDS among HIV-positive PWID have not been completely described. We used data from a community-recruited prospective cohort of HIV-positive PWID in Vancouver, Canada, a setting with universal no-cost ART and a comprehensive clinical monitoring registry. We used multivariable extended Cox models to identify factors associated with time to AIDS. Between 1996 and 2017, 396 participants, including 140 (35.4%) women, were followed for a median of 39.0 months (interquartile range: 16.6–76.2), among whom 165 (41.7%) developed AIDS. In a multivariable model, homelessness (Adjusted Hazard Ratio [AHR] = 1.76 (1.18–2.61)) and injection drug use within the preceding six months (AHR = 1.74 (1.17–2.58)) were independently associated with a higher risk of developing AIDS. Despite widespread scale-up of programmes to improve ART utilization, significant risk factors for the development of AIDS remain among HIV-positive PWID in this setting. [ABSTRACT FROM AUTHOR]

Objectives Despite the high burden of hepatitis C virus ( HCV)-related morbidity and mortality among HIV-positive people who use illicit drugs ( PWUD), uptake of interferon-based treatments for HCV infection has been negligible among this group. Direct-acting antiviral ( DAA) therapies offer an opportunity to expand treatment access among this population. The aim of this study was to explore willingness to use DAA-based regimens among HIV/ HCV-coinfected PWUD in Vancouver, Canada. Methods Data were drawn from the AIDS Care Cohort to evaluate Exposure to Survival Services ( ACCESS), a prospective cohort of HIV-positive PWUD. Using logistic regression analyses, we investigated factors associated with willingness to use DAA-based regimens among HIV/ HCV-coinfected participants. Results Of 418 HIV/ HCV-coinfected PWUD surveyed between June 2014 and May 2015, 295 (71%) were willing to use DAA-based regimens. In multivariable analysis, participants enrolled in methadone maintenance therapy [adjusted odds ratio ( AOR) 1.61; 95% confidence interval ( CI) 1.04-2.51], those with a recent assessment by an HCV specialist ( AOR 2.02; 95% CI 1.28-3.19) and those who perceived that HCV infection was affecting their health ( AOR 2.49; 95% CI 1.41-4.37) were more likely to be willing to use DAA-based regimens. Conclusions Overall, this study found a high prevalence of willingness to use DAA-based regimens among HIV/ HCV-coinfected PWUD in Vancouver. Importantly, enrolment in methadone maintenance therapy was positively associated with willingness, suggesting that integrated models of HIV, HCV and addiction care should be explored as a way to address HCV-related morbidity and mortality among HIV/ HCV-coinfected PWUD. [ABSTRACT FROM AUTHOR]

Objectives HIV treatment-as-prevention campaigns emphasize early diagnosis and immediate access to care and antiretroviral therapy for HIV-positive individuals in order to increase levels of plasma HIV RNA viral load ( VL) suppression. However, the possible role of harm reduction-based programmes in this objective has not yet been well evaluated. The objective of the study was to examine the relationship between being a client of the Dr. Peter Centre ( DPC; an HIV/ AIDS-focused adult integrated health programme) and VL suppression among highly active antiretroviral therapy ( HAART)-exposed HIV-positive people who use illicit drugs ( PWUD) in Vancouver, Canada. Methods Data were derived from the AIDS Care Cohort to Evaluate Exposure to Survival Services ( ACCESS) study, a study of a community-recruited cohort of HIV-positive PWUD. A marginal structural model using inverse probability of treatment weights was used to estimate the longitudinal relationship between being a DPC client and exhibiting a VL < 50 HIV-1 RNA copies/mL plasma. Results Between 2005 and 2014, 746 HAART-exposed participants were included in the study, of whom 269 (36.1%) reported being a DPC client at some time during the study period. A marginal structural model estimated a 1.54 greater odds of achieving VL suppression (95% confidence interval 1.20-1.99) among DPC clients. Conclusions Our findings demonstrate that participating in an innovative HIV/ AIDS-focused adult integrated health programme that provides a broad range of clinical, harm reduction, and support services may contribute to optimizing the benefits of HAART in terms of morbidity, mortality and viral transmission among PWUD, and as a result help to fulfill the goals of the treatment-as-prevention strategy. [ABSTRACT FROM AUTHOR]

Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT)., Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID)., Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), or new conditions that developed beyond 2 years after HCT (late)., Results: The cumulative incidence of CLE was 25% in those alive at 2 years, increasing to 41% at 15 years after HCT. CLE were most prevalent in the neurologic (9%), neurodevelopmental (8%), and dental (8%) categories. Chemotherapy-based conditioning was associated with decreased-height z score at 2 to 5 years after HCT (P < .001), and with endocrine (P < .001) and dental (P = .05) CLE. CD4 count of ≤500 cells/μL and/or continued need for immunoglobulin replacement therapy >2 years after transplantation were associated with lower-height z scores. Continued survival from 2 to 15 years after HCT was 90%. The presence of any CLE was associated with increased risk of late death (hazard ratio, 7.21; 95% confidence interval, 2.71-19.18; P < .001)., Conclusion: Late morbidity after HCT for SCID was substantial, with an adverse impact on overall survival. This study provides evidence for development of survivorship guidelines based on disease characteristics and treatment exposure for patients after HCT for SCID., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: The proliferation of fentanyl and its analogs in illegal, unregulated drug markets remains a major driver of the overdose crisis in North America. Drug checking services have been implemented as a harm reduction strategy to address the crisis. However, little is known about their potential utility as a mechanism for monitoring population-level risk of overdose stemming from changing fentanyl concentration in unregulated drugs over time. Therefore, this study assessed the relationship between median fentanyl concentration in expected opioid drug checking samples and the death rate due to illicit drug toxicity over time in Vancouver, Canada., Methods: Monthly population-based rates of death due to illicit drug toxicity were drawn from provincial coroner records. Monthly median percent fentanyl concentration was calculated using a validated quantification model from point-of-care Fourier-transform infrared spectra among expected opioid samples that tested positive for fentanyl at community drug checking services. A time-series analysis using generalized additive modeling was conducted to examine the association between monthly median fentanyl concentration and monthly death rate due to illicit drug toxicity, controlling for calendar month. Analyses were conducted in 2021-2022., Results: Between January 2019 and October 2020, 577 deaths due to illicit drug toxicity occurred in Vancouver, and the observed monthly rate ranged from 1.75 to 7.65 deaths per 100,000 population. A significant, positive association was observed between monthly median fentanyl concentration and monthly death rate due to illicit drug toxicity, adjusting for calendar month (chi-square=52.21, p<0.001)., Conclusions: Findings suggest a role for point-of-care drug checking as a tool for monitoring evolving overdose risk at the population level., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Optimal dosing of opioid agonist therapy (OAT) is essential for treatment success. However, initiation and maintenance of OAT in hospital settings can be challenging given differing levels of opioid tolerance, withdrawal, and intoxication among patients., The objective of this study was to characterize the prevalence and factors associated with in-hospital patient perceived suboptimal OAT dosing among people who use illicit drugs (PWUD) in Vancouver, Canada., Data were derived from three prospective cohorts of PWUD in Vancouver, Canada. Bivariable and multivariable logistic regression models were used to examine factors associated with patient perceived suboptimal in-hospital OAT dose., 273 study participants were prescribed OAT while in hospital: 83 (30.4%) participants perceived their OAT dose to be suboptimal. In a multivariable model, factors positively associated with a perceived suboptimal OAT dose included: homelessness (adjusted odds ratio [AOR] = 2.85; 95% CI: 1.53-5.28), daily stimulant use (AOR = 2.03; 95% CI: 1.14-3.63) and illicit drug use while in hospital (AOR = 2.33; 95% CI: 1.31-4.16)., Almost one third of participants perceived receiving a suboptimal OAT dose while in hospital. These observed correlations indicate that a patient's perception of suboptimal OAT dosing in hospital may be more prevalent for patients who are homeless, report polysubstance use with stimulants and opioids and who obtain illicit drugs while hospitalized. While cautious prescribing of OAT in patients experiencing hospitalization is important, these findings demonstrate a high prevalence of and apparent risk factors for perceived suboptimal OAT dosing.

Objectives: A managed alcohol program (MAP) is a harm reduction strategy that provides regularly, witnessed alcohol to individuals with a severe alcohol use disorder. Although community MAPs have positive outcomes, applicability to hospital settings is unknown. This study describes a hospital-based MAP, characterizes its participants, and evaluates outcomes., Methods: A retrospective chart review of MAP participants was conducted at an academic hospital in Vancouver, Canada, between July 2016 and October 2017. Data included demographics, alcohol/substance use, alcohol withdrawal risk, and MAP indication. Outcomes after MAP initiation included the change in mean daily alcohol consumption and liver enzymes., Results: Seventeen patients participated in 26 hospital admissions: 76% male, mean age of 54 years, daily consumption prehospitalization of a mean 14 alcohol standard drinks, 59% reported previous nonbeverage alcohol consumption, and 41% participated in a community MAP. Most participants were high risk for severe, complicated alcohol withdrawal and presented in moderate withdrawal. Continuation of community MAP was the most common indication for hospital-based MAP initiation (38%), followed by a history of leaving hospital against medical advice (35%) and hospital illicit alcohol use (15%). Hospital-based MAP resulted in a mean of 5 fewer alcohol standard drinks daily compared with preadmission ( P = 0.002; 95% confidence interval, 2-8) and improvement in liver enzymes, with few adverse events., Conclusions: Participation in a hospital-based MAP may be an effective safe approach to reduce harms for some individuals with severe alcohol use disorder. Further study is needed to understand who benefits most from hospital-MAP and potential benefits/harms following hospital discharge., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Objective: Retaining adolescents and young adults (AYA) in medications for opioid use disorder (MOUD), like methadone maintenance treatment (MMT), is critical to reducing toxic drug fatalities. This analysis sought to identify factors associated with MMT discontinuation among AYA., Method: Data were derived from the At-Risk Youth Study, a prospective cohort study of street-involved AYA in Vancouver, Canada, between December 2005 and June 2018. Multivariable extended Cox regression identified factors associated with time to MMT discontinuation among AYA who recently initiated MMT. In subanalysis, multivariable extended Cox regression analysis identified factors associated with time to "actionable" MMT discontinuation, which could be addressed through policy changes., Results: A total of 308 participants reported recent MMT during the study period. Participants were excluded if they reported MMT in the past 6 months at baseline and were retained in MMT ( n  = 94, 30.5%); were missing MMT status data ( n  = 43, 14.0%); or completed an MMT taper ( n  = 11, 3.6%). Of the remaining 160 participants who initiated MMT over the study period, 102 (63.8%) discontinued MMT accounting for 119 unique discontinuation events. In multivariable extended Cox regression, MMT discontinuation was positively associated with recent weekly crystal methamphetamine use (adjusted hazard ratio [AHR] = 1.67, 95% confidence interval [CI]: 1.19 to 2.35), but negatively associated with age of first "hard" drug use (per year older) (AHR = 0.95, 95% CI: 0.90 to 1.00) and female sex (AHR = 0.66, 95% CI: 0.44 to 0.99). In subanalysis, recent weekly crystal methamphetamine use (AHR = 4.61, 95% CI: 1.78 to 11.9) and weekly heroin or fentanyl use (AHR = 3.37, 95% CI: 1.21 to 9.38) were positively associated with "actionable" MMT discontinuation, while older age (AHR = 0.87, 95% CI: 0.76 to 0.99) was negatively associated., Conclusions: Efforts to revise MMT programming; provide access to a range of MOUD, harm reduction, and treatments; and explore coprescribing stimulants to AYA with concurrent stimulant use may improve treatment retention and reduce toxic drug fatalities.

Our objective was to externally validate 2 simple risk scores for mortality among a mostly inpatient population with COVID-19 in Canada (588 patients for COVID-NoLab and 479 patients for COVID-SimpleLab). The mortality rates in the low-, moderate-, and high-risk groups for COVID-NoLab were 1.1%, 9.6%, and 21.2%, respectively. The mortality rates for COVID-SimpleLab were 0.0%, 9.8%, and 20.0%, respectively. These values were similar to those in the original derivation cohort. The 2 simple risk scores, now successfully externally validated, offer clinicians a reliable way to quickly identify low-risk inpatients who could potentially be managed as outpatients in the event of a bed shortage. Both are available online (https://ebell-projects.shinyapps.io/covid&#95;nolab/ and https://ebell-projects.shinyapps.io/COVID-SimpleLab/)., (© 2022 Annals of Family Medicine, Inc.)

Objectives: Driven by an increasingly toxic drug supply, drug toxicity deaths in the United States and Canada have risen to unprecedented levels during the COVID-19 pandemic. This study aimed to characterize the prevalence of and the factors associated with a perceived decline in the quality of drugs during the COVID-19 pandemic among community-recruited cohorts of PWUD in Vancouver, Canada., Methods: Data collection took place between July and November 2020. In adherence with COVID-19 safety protocols, questionnaires were administered by interviewers through remote means (e.g., phone or videoconference). Using multivariable logistic regression, we characterized the prevalence of and factors associated with a perceived decline in drug quality during the start of the COVID-19 pandemic in Vancouver, Canada., Results: Of the 738 individuals included in this analysis, 272 (36.9%) reported that the quality of drugs declined during the COVID-19 pandemic. In multivariable analysis, perceived decline in the quality of drugs was significantly associated with: recent non-fatal overdose (adjusted odds ratio [AOR]=2.01, 95% Confidence Interval [CI]: 1.29-3.15), at least weekly injection drug use (AOR=1.94, 95% CI: 1.40-2.71), at least weekly crack use (AOR=1.61, 95%CI: 1.10-2.36), and at least weekly crystal methamphetamine use (AOR=1.46, 95%CI: 1.03-2.08)., Discussion: Over a third of PWUD perceived that the quality of drugs declined during the COVID-19 pandemic and these individuals were significantly more likely to report experiencing a recent non-fatal overdose, engaging in frequent injection drug and stimulant use. Study findings indicate the need for interventions to address the toxic drug supply, including providing a regulated supply., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Methamphetamine use is rising globally and we have limited treatments for this. Subgroups within the diverse methamphetamine-using population may have distinct treatment needs. Among a community-recruited sample of people who use crystal methamphetamine, we aimed to identify subgroups and characterize their overdose risk and access to addiction care., Methods: Data from prospective cohorts of people who use drugs in Vancouver, Canada from 2014 to 2018 were used to conduct a repeated measures latent class analysis among participants who used crystal methamphetamine. Multivariable generalized estimating equations models were fit to determine the associated factors., Results: Among 824 eligible participants, a five-class model was identified as the best fit: (1) primary stimulant use (15.7%); (2) women engaged in sex work and opioid use (21.4%); (3) street income generation and opioid use (31.6%); (4) opioid agonist therapy (OAT) patients (22.3%); and (5) men who have sex with men (9.0%). In multivariable analyses, compared to the primary stimulant use group, non-fatal overdose was positively associated with street income generation (adjusted odds ratio [AOR] = 1.49, 95% confidence interval [95% CI]=1.30-1.71), sex work (AOR = 1.38, 95% CI=1.20-1.59) and OAT (AOR = 1.22, 95% CI=1.06-1.41) subgroups; engagement in non-OAT addiction care was negatively associated with street income generation (AOR = 0.81, 95% CI=0.68-0.97) and sex work (AOR = 0.78, 95% CI=0.63-0.98) subgroups., Discussion: Socioeconomically marginalized subgroups with opioid and crystal methamphetamine co-use were at highest risk of non-fatal overdose and had poorer access to addiction care, highlighting the need for tailored interventions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: High levels of morbidity and mortality associated with injection drug use continue to represent a significant public health challenge in many settings worldwide. Previous studies have shown an association between cannabis use and decreased risk of some drug-related harms. We sought to evaluate the association between high-intensity cannabis use and the frequency of injection drug use among people who inject drugs (PWID). Methods: The data for this analysis were collected from three prospective cohorts of PWID in Vancouver, Canada, between September 2005 and May 2018. Generalized linear mixed-effects models were used to analyze the association between daily cannabis use and the frequency of injecting illegal drugs (i.e., self-reported average number of injections per month). Results: Among the 2,619 active PWID, the frequency of injection drug use was significantly lower among people who use cannabis daily compared with people who use it less than daily (adjusted odds ratio [AOR]=0.84, 95% confidence interval [CI]: 0.73-0.95). Sub-analyses indicated that this effect was restricted to the frequency of illegal opioid injection (AOR=0.78, 95% CI: 0.68-0.90); the association between daily cannabis use and the frequency of illegal stimulant injection was not significant (AOR=1.08, 95% CI 0.93-1.25). Discussion: The findings from these prospective cohorts suggest that people who use cannabis daily were less likely to report daily injection of illegal drugs compared with people who use it less than daily. These results suggest the potential value of conducting experimental research to test whether controlled administration of cannabinoids impacts the frequency of illegal opioid injection among PWID.

Introduction: Illicitly manufactured fentanyl continues to fuel the opioid overdose crisis throughout the USA and Canada. However, little is known about factors associated with knowingly or unknowingly using fentanyl. Therefore, we sought to identify the prevalence and correlates of suspected/known and unknown exposure to fentanyl (excluding the prescribed one) among people who inject drugs (PWID), including associated overdose risks., Methods: Data were derived from three prospective cohort studies of community-recruited people who use drugs in Vancouver, Canada in 2016-2017. Multivariable logistic regression was used to identify correlates of suspected/known exposure (i.e. urine drug screen positive and self-reporting past 3-day exposure) and unknown exposure to fentanyl (i.e. urine drug screen positive and self-reporting no past three-day exposure), respectively., Results: Among 590 PWID, 296 (50.2%) tested positive for fentanyl. Of those, 143 (48.3%) had suspected/known and 153 (51.7%) had unknown exposure to fentanyl. In multivariable analyses, using supervised injection sites and possessing naloxone were associated with both suspected/known and unknown exposure (all P < 0.05). Injecting drugs alone (adjusted odds ratio 3.26; 95% confidence interval: 1.72-6.16) was associated with known exposure, but not with unknown exposure., Discussion and Conclusions: We found a high prevalence of fentanyl exposure in our sample of PWID, with one half of those exposed consuming fentanyl unknowingly. While those exposed to fentanyl appeared more likely to utilise some overdose prevention services, PWID with suspected/known fentanyl exposure were more likely to inject alone, indicating a need for additional overdose prevention efforts for this group., (© 2021 Australasian Professional Society on Alcohol and other Drugs.)

Background: Settings throughout the United States and Canada are contending with high rates of drug-related overdose. This in turn has prompted efforts to more effectively engage people who use drugs (PWUD) in treatment and care. However, while co-morbid mental disorders are prevalent among PWUD and can undermine access to services, the impact of post-traumatic stress disorder (PTSD) on service access is not known. Therefore, we sought to assess whether PTSD is associated with difficulties accessing health and social services among PWUD in Vancouver, Canada., Methods: Survey data was derived from two prospective cohorts of PWUD in Vancouver, Canada for the period of April 2017 to November 2018. PTSD was assessed using the PTSD Checklist for the DSM-V (PCL-5). Generalized estimating equations (GEE) was used to estimate the relationship between PTSD and self-reported inability to access health and social services, after adjustment for confounders., Results: Among 810 participants included in our analysis, 316 (39.0%) participants qualified for a provisional PSTD diagnosis, and 117 (14.4%) reported difficulties accessing services. In a multivariable GEE analysis, a PTSD diagnosis (adjusted odds ratio = 1.69, 95% confidence interval: 1.12-2.55) was independently associated with difficulties accessing services., Conclusions: We found high rates of PTSD and self-reported difficulties accessing services among PWUD in Vancouver, as well as a positive association between PTSD and difficulties with service access. These findings highlight the need for trauma-informed approaches to service delivery for PWUD, as well as enhanced provider training specific to PTSD.

Background: While exposure to traumatic events and subsequent post-traumatic stress disorder (PTSD) are common among people who use drugs (PWUD), little is known about gender-based differences associated with PTSD in this population. We explore gender-based differences in factors associated with a probable PTSD diagnosis in a cohort of PWUD from Vancouver, Canada., Methods: Data were collected through the Vancouver Injection Drug Users Study (VIDUS) and the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS), two community-recruited cohorts of PWUD. Participants were administered the PTSD Checklist for DSM-5. Multivariable logistic regression was used to investigate social-structural factors and substance use patterns and behaviours associated with a probable PTSD diagnosis, stratified by self-identified gender. PTSD symptom clusters and brief descriptions of the worst traumatic event experienced were also reported., Results: Between December 2016 and December 2018, of 797 eligible participants, 295 (37.0%) identified as women. PTSD was more commonly reported in women compared to men (53.2% vs. 31.5%, p < 0.001). In multivariable analysis involving men, no correlates were associated with PTSD. In multivariable analysis involving women, PTSD was positively associated with exposure to violence (AOR: 3.66; 95%CI: 1.14-11.72), daily stimulant use (AOR: 2.32; 95%CI: 1.32-4.08) and heavy alcohol use (AOR: 3.84; 95%CI: 1.84-8.00), and negatively associated with being in a stable relationship (AOR: 0.46; 95%CI: 0.25-0.84)., Conclusions: Gender-based differences in PTSD diagnosis among a cohort of PWUD point to the need to develop gender-focused and trauma-informed health and social services to meet the immediate needs of PWUD living with PTSD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Aims: Income assistance is critical to the health and wellbeing of socio-economically marginalized people who use illicit drugs (PWUD). However, past literature paradoxically identifies unintended increases in drug-related harm coinciding with synchronized payments that may magnify signals for drug use. The scope of such harm has not been fully characterized among non-institutionalized populations. This study examined socio-demographic, health and drug use-related correlates of payment-coincident drug-related harm., Design: This observational study uses data from prospective community-based longitudinal cohorts of PWUD between December 2013 and May 2018., Setting: Vancouver, British Columbia, Canada., Participants: A total of 1604 PWUD receiving monthly income assistance. Our sample included 586 (36.5%) women, 861 (53.7%) non-white participants and 685 (42.7%) people living with HIV., Measurements: The primary outcome was a self-reported composite measure of drug-related harm in the past 6 months coinciding with income assistance, including higher-frequency substance use, non-fatal overdose and service barriers or interruptions. Subanalyses disaggregated this outcome., Findings: Payment-coincident drug-related harm was reported among 77.7% of participants during the study period. In multivariable models, key correlates positively and significantly associated with payment-coincident harm included: street-based income generation [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI) = 1.26-1.74, P < 0.001], sex work (aOR = 1.66, 95% CI = 1.35-2.04, P < 0.001), illegal income generation (aOR = 1.57, 95% CI = 1.35-1.83 P < 0.001), homelessness (aOR = 1.34, 95% CI = 1.13-1.58, P < 0.001), exposure to violence (aOR = 1.31, 95% CI = 1.03-1.66, P = 0.032), daily crack cocaine use (aOR = 1.99, 95% CI = 1.59-2.50, P <  0.001), heavy alcohol use (aOR = 1.64, 95% CI = 1.37-1.97, P < 0.001) and injection drug use (aOR = 2.55, 95% CI = 2.01-3.23, P < 0.001). In subanalyses, specific harms were more likely among individuals reporting social, structural and health vulnerabilities., Conclusions: In Vancouver, Canada, people who use illicit drugs who receive income assistance report high prevalence of payment-coincident drug-related harm, particularly people experiencing socioeconomic and structural marginalization or engaging in high-intensity drug use., (© 2020 Society for the Study of Addiction.)

Background: Opioid agonist therapy (OAT) models are generally provided without consideration of how pre-treatment characteristics may be associated with outcome. Therefore, we aimed to first characterize longitudinal trajectories of opioid use before initiating OAT. Then we explored the impact of OAT on opioid use across these pre-treatment trajectories., Methods: Data were derived from three prospective cohort studies involving people who use drugs in Vancouver, Canada. Latent class growth analysis was applied to identify opioid use trajectories based on individual-level observations three years before starting OAT. Multivariable generalized linear mixed model was used to examine whether engaging in OAT was associated with lower risk of illicit opioid use among participants with different pre-treatment opioid use trajectories., Results: 464 participants were included in the study between September 2005 and November 2018. Two pre-treatment opioid use trajectories were identified: high frequency users (246, 53.0%) and gradually increasing frequency users (218, 47.0%). We observed different strengths of association between OAT engagement and illicit opioid use among high frequency users (adjusted odds ratio [AOR] = 0.36, 95% Confidence Interval [CI]: 0.20 - 0.63) and gradually increasing frequency users (AOR = 0.91, 95% CI: 0.53 - 1.56). Unstable housing, any stimulant use, experiencing violence, drug dealing, sex work involvement, and incarceration were independently and positively associated with ongoing illicit opioid use., Conclusions: Distinct pre-treatment opioid use trajectories are likely to influence treatment outcomes. Research is required to determine if tailored strategies specific to people with different pre-treatment opioid use patterns have potential to improve outcomes of OAT., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Retention in opioid agonist therapy consistently has been linked with improved outcomes among people with opioid use disorder. However, less is known about the links between patterns of engagement in opioid agonist therapy over the long term and overdose risk. This study assesses the association of opioid agonist therapy retention trajectories with nonfatal overdose., Methods: Data were drawn from 2 community-recruited prospective cohorts of people who use drugs in Vancouver, Canada. Latent class growth analysis was used to identify trajectories of opioid agonist therapy retention among people with opioid use disorder initiating therapy, and generalized estimating equations assessed the association of these trajectories with nonfatal overdose events after opioid agonist therapy initiation., Results: Between 2005 and 2018, among 438 opioid agonist therapy initiators, 4 retention trajectories were identified: consistently high (35.6%), increasing (26.0%), consistently low (23.3%), and decreasing (15.1%) opioid agonist therapy engagement. During the study period, there were 371 nonfatal overdose events, with 179 (40.1%) participants reporting ≥1. In adjusted analysis, the consistently low (AOR=1.73, 95% CI=1.10, 2.71) and decreasing (AOR=1.87, 95% CI=1.18, 2.95) retention trajectories were positively associated with increased odds of nonfatal overdose compared with the consistently high opioid agonist therapy retention class., Conclusions: Suboptimal trajectories of opioid agonist therapy retention were associated with an increased likelihood of nonfatal overdose. These findings suggest that reducing the barriers to sustained engagement in opioid agonist therapy will be critical to address North America's overdose epidemic., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: People who use illicit drugs (PWUD) experience various adverse health outcomes leading to increased healthcare service utilization. PWUD are also a highly mobile population which poses challenges to healthcare delivery. The objective of this study was to identify migration patterns from the Downtown Eastside (DTES), an urban illicit drug scene in Vancouver and to estimate the impact of different migration patterns on two outcomes: a) emergency department (ED) visits and b) ED visits resulting in inpatient admission among PWUD., Methods: Three prospective cohorts of PWUD in Vancouver were linked with regional ED data. We defined the optimal number of trajectory groups that best represented distinct patterns of migration from Vancouver's DTES using a latent class growth analysis. Then, generalized estimating equations were used to estimate the effect of migration patterns on the two ED outcomes., Results: Four distinct migration trajectory patterns were identified among the 1210 included participants: PWUD who consistently lived in the DTES, those who migrated out of DTES early, those who migrated out of DTES late, and those who frequently revisited the DTES. Participants who frequently revisited the DTES had higher odds of an ED visit (adjusted odds ratio = 1.62; 95% confidence interval: 1.28-2.06). There was no significant association between migration patterns and inpatient admission., Conclusions: We found that PWUD who frequently revisited the DTES were more likely to have utilized the ED, suggesting that there may be a subgroup of PWUD who are at increased risk of experiencing negative health outcomes.Supplemental data for this article is available online at 10.1080/10826084.2021.1958849.

Introduction and Aims: People who use illicit drugs (PWUD) are vulnerable to an array of negative health outcomes, and increased hospital services utilisation. PWUD are also a transient population which poses challenges to the provision of optimal health care. The objective of this study was to identify out-migration patterns from Vancouver's Downtown Eastside (DTES), a neighbourhood where services for PWUD are concentrated, and to estimate the impact of these patterns on hospitalisation events among PWUD., Design and Methods: Data were collected through three prospective cohorts of PWUD in Vancouver, which were linked with health administrative data. Latent class growth analysis was used to define migration trajectory groups. Poisson regression was used to estimate the effect of migration patterns on hospitalisation events., Results: A total of 1180 participants were included in the study. Four latent classes were identified: early migration out (243, 20.6%); frequent revisit (112, 9.5%); late migration out (219, 18.6%); and consistently living in the DTES (606, 51.4%). Compared with those who consistently lived in the DTES, participants in the early migration out group had lower hospitalisation events (adjusted rate ratio = 0.65; 95% confidence interval: 0.48-0.90)., Discussion and Conclusion: We found that PWUD who migrated out of the DTES early had lower hospitalisation events compared to those who consistently lived in the DTES, which may be a function of lesser addiction severity among this trajectory group. These findings underscore a need to provide transitional health and social service supports for other trajectory groups in an effort to minimise hospitalisation for preventable causes., (© 2020 Australasian Professional Society on Alcohol and other Drugs.)

Background: Although previous studies have shown that opioid agonist therapy (OAT) is linked to reductions in illicit opioid use, less is known about how OAT impacts the use of other psychoactive substances. We aimed to examine the changes in use of different substances by comparing patterns before and after initiating OAT., Methods: Data for this study was derived from three ongoing prospective cohorts involving people who use drugs in Vancouver, Canada from 1996 to 2018. We assessed use patterns for heroin, illicit prescription opioid, cocaine, crack cocaine, crystal methamphetamine, cannabis, daily alcohol use, and benzodiazepines. Segmented regression was conducted to compare the trends of substance use between pre-treatment and post-treatment periods., Results: The study included 1107 participants. After OAT engagement, we observed an immediate decline in the proportion as well as a decreasing trend for heroin (Adjusted Odds Ratio (AOR): 0.80, 95% confidence interval (CI): 0.77, 0.83), illicit prescription opioid (AOR: 0.87, 95% CI: 0.83, 0.90), and benzodiazepines (AOR: 0.73, 95 % CI: 0.67, 0.80). There was no significant difference comparing the pre-treatment and post-treatment trends for cocaine, crack cocaine, crystal methamphetamine, and cannabis. However, higher growth slope was noted during the post-treatment period for daily alcohol use (P = 0.016)., Conclusions: We observed significant reduction in illicit opioids use following OAT initiation, but not for stimulant and cannabis. The increasing problematic use of alcohol may pose challenges to the safety and effectiveness of OAT. Development of comprehensive and tailored treatment strategies is needed for poly-substance users accessing OAT., Competing Interests: Declaration of Competing Interest The University of British Columbia has received an unstructured gift from NG Biomed Ltd., a private firm seeking a license to produce medical cannabis, to support Dr. M.-J. Milloy. He is the Canopy Growth professor of cannabis science at the University of British Columbia, a position created using unstructured gifts to the university from Canopy Growth, a licensed producer of cannabis, and the Government of British Columbia’s Ministry of Mental Health and Addictions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: Injection drug use patterns are known to change over time, although such long-term changes have not been well described. We sought to characterize longitudinal trajectories of injection drug use and identify associated factors., Design: Data were derived from the Vancouver Injection Drug Users Study and AIDS Care Cohort to evaluate the Exposure to Survival Services study, two prospective cohorts involving people who inject drugs in Vancouver, Canada between 1996 and 2017. Growth mixture modeling was applied to identify distinct injection drug use trajectories. Multinomial logistic regression was used to identify baseline factors associated with each trajectory., Setting: Canada., Participants: A total of 2057 participants who reported having used illicit drugs via injection in the past 6 months at the baseline visit were included in the study. The median time since first injection drug use at baseline was 14.8 years (quartile 1-quartile 3: 6.5-24.3)., Measurements: Information regarding self-reported injection drug use during the past 6 months was collected at baseline and semi-annually thereafter via interviewer-administered questionnaires., Findings: Participants were followed for a median of 113.4 months (quartile 1-quartile 3: 63.4-161.7). Five trajectories were identified: persistent high frequency injection (507, 24.6%); high frequency injection with late decrease (374, 18.2%); gradual cessation (662, 32.2%); early cessation with late relapse (227, 11.0%); and early cessation (287, 14.0%). Factors found to be associated with distinct trajectories included: daily heroin injection, binge injection drug use, age, not being in a stable relationship and year of study enrollment., Conclusions: People who used drugs in Vancouver, Canada from 1996 to 2017 appeared to follow five drug use trajectories, ranging from persistent high frequency use to early cessation. Almost 25% of participants remained high-frequency injectors over the study period., (© 2019 Society for the Study of Addiction.)

Background: Urban drug scenes are characterized by high prevalence of illicit drug dealing and use, violence and poverty, much of which is driven by the criminalization of people who use illicit drugs (PWUD) and the associated stigma. Despite significant public health needs, little is understood about patterns of moving into urban drug scenes among PWUD. Therefore, we sought to identify trajectories of residential mobility (hereafter 'mobility') among PWUD into the Downtown Eastside (DTES), an urban neighbourhood with an open drug scene in Vancouver, Canada, as well as characterize distinct trajectory groups among PWUD., Methods: Data were derived from three prospective cohort studies of community-recruited PWUD in Vancouver between 2005 and 2016. We used latent class growth analysis (LCGA) to identify distinct patterns of moving into the DTES among participants residing outside of DTES at baseline. Multivariable multinomial logistic regression was used to determine baseline factors associated with each trajectory group., Results: In total, 906 eligible participants (30.9% females) provided 9,317 observations. The LCGA assigned four trajectories: consistently living outside of DTES (52.8%); early move into DTES (11.9%); gradual move into DTES (19.5%); and move in then out (15.8%). Younger PWUD, those of Indigenous ancestry, those who were homeless or living in a single-room occupancy hotel (SRO), and those injecting drugs daily were more likely to move in then out of DTES (all p<0.05). Living in an SRO, daily injection drug use, and recent incarceration were also positively associated with early mobility (all p<0.05)., Conclusions: Nearly half of the participants moved into the DTES. Younger PWUD and Indigenous peoples appeared to have particularly high mobility, as did those with markers of social-structural vulnerability and high intensity drug use. These findings indicate a need to tailor existing social and health services within the DTES and expand affordable housing options outside the DTES., Competing Interests: MJM’s institution (the University of British Columbia) has received an unstructured gift from NG Biomed, Ltd., to support him. The funder did not play any role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript. Further, this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Although the health and community benefits of supervised injection facilities are well documented, little is known about long-term patterns of utilization of this form of health service. The present study seeks to longitudinally characterize discontinuation of use of a supervised injection facility in Vancouver, Canada., Methods: Data were drawn from 2 community-recruited prospective cohorts of people who inject drugs between December 2005 and December 2016. In 2018, extended Cox regression for recurrent events was used to examine factors associated with time to cessation of supervised injection facility use during periods of active injection., Results: Of 1,336 people who inject drugs that were followed for a median of 50 months, 847 (63.4%) participants reported 1,663 6-month periods of supervised injection facility use cessation while actively injecting drugs (incidence density of 26.6 events per 100 person-years). An additional 2,282 (57.8%) of the total 3,945 6-month periods of supervised injection facility use cessation occurred during periods of injection cessation. In multivariable analyses, enrollment in methadone maintenance therapy (adjusted hazard ratio=1.41) and HIV seropositivity (adjusted hazard ratio=1.23) were positively associated with supervised injection facility use cessation during periods of active injection, whereas homelessness (adjusted hazard ratio=0.59), at least daily heroin injection (adjusted hazard ratio=0.70), binge injection (adjusted hazard ratio=0.68), public injection (adjusted hazard ratio=0.67), nonfatal overdose (adjusted hazard ratio=0.73), difficulty accessing addiction treatment (adjusted hazard ratio=0.69), and incarceration (adjusted hazard ratio=0.70) were inversely associated with this outcome (all p<0.05). The most commonly reported reasons for supervised injection facility use cessation were injection drug use cessation (42.3%) and a preference for injecting at home (30.7%)., Conclusions: These findings suggest that this supervised injection facility successfully retains people who inject drugs at elevated risk of drug-related harms and indicate that many supervised injection facility clients neither use this service nor inject drugs perpetually., (Copyright © 2019. Published by Elsevier Inc.)

Background: North America is in the midst of an opioid overdose epidemic. Although take-home naloxone and other measures have been an effective strategy to reduce overdoses, many events are unwitnessed and mortality remains high amongst those using drugs alone. While wearable devices that can detect and alert others of an overdose are being developed, willingness of people who use drugs to wear such a device has not been described., Methods: Drug using persons enrolled in a community-recruited cohort in Vancouver, Canada, were asked whether or not they would be willing to wear a device against their skin that would alert others in the event of an overdose. Logistic regression was used to identify factors independently associated with willingness to wear such a device., Results: Among the 1061 participants surveyed between December 2017 and May 2018, 576 (54.3%) were willing to wear an overdose detection device. Factors independently associated with willingness included ever having overdosed (adjusted odds ratio [AOR] = 1.39, 95% confidence interval [CI] 1.06-1.83), current methadone treatment (AOR = 1.86, 95% CI 1.45-2.40), female gender AOR = 1.41, 95% CI 1.09-1.84) and a history of chronic pain (AOR = 1.53, 95% CI 1.19-1.96). Whereas homelessness (AOR = 0.67, 95% CI 0.50-0.91) was negatively associated with willingness., Conclusions: A high level of willingness to wear an overdose detection device was observed in this setting and a range of factors associated with overdose were positively associated with willingness. Since some factors, such as homelessness may be a barrier, further research is needed to investigate explanations for unwillingness and to evaluate real world acceptability of a wearable overdose detection devices as this technology becomes available.

Throughout the world, Indigenous populations experience a disproportionate burden of HIV infection. Maximally-assisted therapy (MAT) is an interdisciplinary care intervention that includes ART dispensation to support individuals with a history of addiction and homelessness. This study sought to longitudinally evaluate the relationship between engagement in MAT and achieving optimal adherence using data from an ongoing cohort of HIV-positive individuals who use drugs in Vancouver, Canada, where HIV/AIDS treatment is offered at no cost. Between December 2005 and November 2016, 354 HIV-positive Indigenous participants were enrolled and data were analyzed using generalized mixed-effects (GLMM) and marginal structural modeling. In both multivariable analyses, engagement in MAT was independently associated with optimal adherence to ART (GLMM: AOR = 4.92, 95% CI 3.18-7.62; marginal structural model: AOR = 5.76, 95% CI 3.34-9.96). MAT-based programmes could be a part of a renewed evidence-base to elevated levels of preventable HIV/AIDS-associated morbidity, mortality and viral transmission among Indigenous peoples in Canada.

People living with HIV who use illicit drugs continue to experience high rates of suboptimal treatment outcomes from antiretroviral therapy (ART). Although previous studies have identified important behavioural, social and structural barriers to ART adherence, the effects of patient-level factors have not been fully evaluated. Thus, we sought to investigate the prevalence and correlates of reporting ART was difficult to take among a cohort of illicit drug users in Vancouver, Canada. We accessed data from the AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), an ongoing prospective cohort of HIV-positive illicit drug users linked to comprehensive HIV clinical monitoring records. We used generalized linear mixed-effects modeling to identify factors longitudinally associated with periods in which individuals reported they found ART difficult to take. Between December 2005 and May 2014, 746 ART-exposed illicit drug users were recruited and contributed at least one study interview. Finding ART hard to take was reported by 209 (28.0%) participants at baseline, and 460 (61.7%) participants throughout the study period. Patients ingesting a greater daily pill count (adjusted odds ratio [AOR] = 1.12 per pill, 95% confidence interval [CI] 1.08-1.17) and experiencing barriers to healthcare (AOR = 1.64, 95% CI 1.34-2.01) were more likely to report difficulty taking ART. Patients less likely to report satisfaction with their HIV physician (AOR = 0.76, 95% CI 0.58-1.00) and achieve a non-detectable HIV viral load (AOR = 0.62, 95% CI 0.51-0.74) were more likely to report finding ART hard to take. In this community-recruited cohort of ART-exposed illicit drug users, a substantial proportion reported they found HIV treatment hard to take, which was clearly linked to higher dissatisfaction with healthcare experiences and, most importantly, a lower likelihood of experiencing optimal virologic outcomes. Our findings reveal a number of opportunities to improve HIV treatment experiences and outcomes for people who use illicit drugs, including the use of treatment regimens with lower pill burdens, as well as reducing barriers to healthcare access.

Syringe sharing places street-involved young people at risk of acquiring HIV and hepatitis C. While markers of economic marginalization, such as homelessness, have been linked with syringe sharing and have led to targeted interventions, the relationship between syringe sharing and other markers of economic vulnerability, such as sex work, are not well documented among young people. This study examines whether those engaged in sex work are at increased risk of syringe borrowing and syringe lending among street-involved youth who use injection drugs in Vancouver, Canada. Between September 2005 and May 2014, data was collected from the At-Risk Youth Study (ARYS), a prospective cohort of street involved youth aged 14-26. Generalized estimating equations with a confounding model building approach was used to examine the relationship between sex work and syringe borrowing and lending. 498 youth reported injecting drugs at some point during the study period and were therefore included in the analysis. In multivariable analysis, youth who engaged in sex work were at an elevated risk of both syringe borrowing (Adjusted Odds Ratio (AOR) = 2.17, 95% Confidence Interval [CI] = 1.40-3.36) and syringe lending (AOR = 1.66, 95% CI = 1.07-2.59). Our study found that youth engaged in street-based sex work were at a significantly higher risk of both syringe borrowing and lending among youth who use injection drugs in Vancouver. Ready access to clean syringes, safer working conditions for sex workers to enable risk reduction measures, and increased access to addiction treatment are identified as promising opportunities for reducing syringe sharing in this setting.

Background: Active illicit drug use can present a barrier to the medical management of HIV infection by complicating adherence to antiretroviral therapy (ART). Plasma HIV-1 RNA viral load (VL) rebound, defined as a period of detectable HIV VL following ART and VL suppression, can lead to the generation of viral resistance and potential treatment failure. We sought to investigate the contribution of substance use patterns on rates of VL rebound., Methods: We used data from the ACCESS study, a long-running community-recruited prospective cohort of HIV-positive people who use illicit drugs in Vancouver, Canada, a setting of universal no-cost HIV treatment. We analysed time to VL rebound (that is, two consecutive observations ≥1,000 copies/ml) after ART initiation and sustained viral suppression (that is, two consecutive observations <50 copies/ml) using extended Cox regression models with a recurrent events framework., Results: Between May 1996 and November 2013, 564 ART-exposed participants achieved at least one instance of VL suppression and contributed 1,893.8 person-years of observation. Over follow-up, 198 (35.1%) participants experienced ≥ one instance of VL rebound. In adjusted analyses, VL rebound was associated with younger age (adjusted hazard ratio [AHR] =0.97, 95% CI: 0.95, 0.98), heroin injection (≥ daily versus < daily, AHR =1.52, 95% CI: 1.01, 2.30), crack use (≥ daily versus < daily, AHR = 1.73, 95% CI: 1.08, 1.92) and heavy alcohol use (≥ four versus < four drinks/day, AHR =1.97, 95% CI: 1.17, 3.31)., Conclusions: The present study suggests that in addition to heavy alcohol use, high-intensity illicit drug use, particularly ≥ daily heroin injection and ≥ daily crack smoking are risk factors for VL rebound. In addition to the impact of high-intensity drug use on health-care engagement and ART adherence, some evidence exists on the direct impact of psychoactive substances on ART metabolism and the natural progression of HIV disease. At-risk individuals should be provided additional supports to preserve virological control and maintain the benefits of ART.

Background: Nonmedical prescription opioid use (NMPOU) is a serious public health problem in North America. At a population-level, previous research has identified differences in the prevalence and correlates of NMPOU among younger versus older age groups; however, less is known about age-related differences in NMPOU among people who use illegal drugs., Methods: Data were collected between 2013 and 2015 from two linked prospective cohort studies in Vancouver, Canada: the At-Risk Youth Study (ARYS) and the Vancouver Injection Drug Users Study (VIDUS). Factors independently associated with NMPOU among younger (ARYS) and older (VIDUS) participants were examined separately using bivariate and multivariate generalized estimating equations., Results: A total of 1162 participants were included. Among 405 eligible younger participants (Median age = 25; Inter-Quartile Range [IQR]: 22-28), 40% (n = 160) reported engaging in NMPOU at baseline; among 757 older participants (Median age = 48, IQR: 40-55), 35% (n = 262) reported engaging in NMPOU at baseline. In separate multivariate analyses of younger and older participants, NMPOU was positively and independently associated with heroin use (younger: Adjusted Odds Ratio [AOR] = 3.12, 95% Confidence Interval [CI]: 2.08-4.68; older: AOR = 2.79, 95% CI: 2.08-3.74), drug dealing (younger: AOR = 2.22, 95% CI: 1.58-3.13; older: AOR = 1.87, 95% CI: 1.40-2.49), and difficulty accessing services (younger: AOR = 1.47, 95% CI: 1.04-2.09; older: AOR = 1.74, 95% CI: 1.32-2.29). Among the youth cohort only, NMPOU was associated with younger age (AOR = 1.12, 95% CI: 1.05-1.19), crack use (AOR = 1.56, 95% CI: 1.06-2.30), and binge drug use (AOR = 1.41, 95% CI: 1.00-1.97); older participants who engaged in NMPOU were more likely to report crystal methamphetamine use (AOR = 1.97, 95% CI: 1.46-2.66), non-fatal overdose (AOR = 1.76, 95% CI: 1.20-2.60) and sex work (AOR = 1.49, 95% CI: 1.00-2.22)., Discussion: The prevalence of NMPOU is similar among younger and older people who use drugs, and independently associated with markers of vulnerability among both age groups. Adults who engage in NMPOU are at risk for non-fatal overdose, which highlights the need for youth and adult-specific strategies to address NMPOU that include better access to health and social services, as well as a range of addiction treatment options for opioid use. Findings also underscore the importance of improving pain treatment strategies tailored for PWUD.

Introduction and Aims: Street-involved youth are known to be at elevated risk of initiating injection drug use. However, the impact of so-called 'gateway' drugs, such as cannabis, on injection initiation is unknown. The objective of this study was to examine the association between cannabis use and initiation of injection drug use among a prospective cohort of street-involved youth in Vancouver, Canada., Design and Methods: Data for this study were collected from the At-Risk Youth Study. From September 2005 to May 2015, participants aged 14-26 who reported illicit drug use were recruited into this open prospective cohort study. An extended Cox regression model with time-updated covariates was used to identify factors independently associated with injection initiation., Results: During the study period, 481 street-involved youth were included in this study. Of these, 228 (47.4%) reported at least daily cannabis use, and 103 (21.4%) initiated injection drug use. In a multivariable analysis, ≥daily cannabis use was associated with slower rates of injection initiation (adjusted relative hazard 0.66, 95% confidence interval 0.45-0.98; P = 0.038). Sub-analyses revealed that cannabis use was negatively associated with initiation of injection stimulants but not initiation of injection opioids., Discussion and Conclusions: Given the expansion of cannabis legalisation throughout North America, it is encouraging that cannabis use was associated with slower time to initiation of injection drug use in this cohort. This finding challenges the view of cannabis as a gateway substance that precipitates the progression to using harder and more addictive drugs., (© 2018 Australasian Professional Society on Alcohol and other Drugs.)

Objectives: A growing body of evidence supports the effectiveness of injectable diacetylmorphine (i.e., heroin) for individuals with treatment-refractory opioid use disorder. Despite this evidence, and the increasing toll of opioid-associated morbidity and mortality, it remains controversial in some settings. To investigate the possible contribution of heroin-assisted treatment (HAT) to HIV treatment-related outcomes, we sought to estimate the proportion and characteristics of HIV-positive people who inject opioids that might be eligible for HAT in Vancouver, Canada., Methods: We used data from a prospective cohort of people living with HIV who use illicit drugs in Vancouver, Canada. Using generalized estimating equations (GEE), we assessed the longitudinal relationships between eligibility for HAT, using criteria from previous clinical trials and guidelines, with behavioural, social, and clinical characteristics., Results: Between 2005 and 2014, 478 participants were included in these analyses, contributing 1927 person-years of observation. Of those, 94 (19.7%) met eligibility for HAT at least once during the study period. In a multivariable GEE model, after adjusting for clinical characteristics, being eligible for HAT was positively associated with homelessness, female gender, high-intensity illicit drug use, drug dealing and higher CD4 count., Conclusions: In our study of HIV-positive people with a history of injection drug use, approximately 20% of participants were eligible for HAT at ≥ 1 follow-up period. Eligibility was linked to risk factors for sub-optimal HIV/AIDS treatment outcomes, such as homelessness and involvement in the local illicit drug trade, suggesting that scaling-up access to HAT might contribute to achieving optimal HIV treatment in this setting.

Background and Aim: Although methadone, an opioid agonist, has been an effective medication used to treat opioid use disorder for over 40years, recent studies have found that methadone was identified in more than a quarter of prescription opioid-related deaths among people who use illicit drugs in Vancouver, Canada. Thus, we sought to longitudinally examine the availability of diverted methadone among people who inject drugs (PWID)., Design and Methods: Data were collected from three prospective cohorts of PWID in Vancouver, Canada between December 2005 and May 2015. Multivariable generalized estimating equation logistic regression was used to identify temporal trends in the immediate availability of diverted methadone (defined as the ability to acquire illicit methadone in <10min)., Results: A total of 2092 participants, including 727 (34.8%) women, were included in the present study. In the multivariable analyses after adjusting for a range of potential confounders, later calendar year (adjusted odds ratio [AOR]=1.21 per year; 95% confidence interval [CI]: 1.19-1.23) was independently and positively associated with reporting immediate availability of diverted methadone., Conclusions: We observed a significant increase in the reported availability of diverted methadone among PWID over a ten-year follow-up period. Further research is needed to identify strategies to limit methadone diversion and assess the impact of alternative medications that are equally effective but safer, such as buprenorphine/naloxone., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Nonmedical use of prescription opioid and illicit opioid has been increasing at an alarming rate in North America over the past decade., Objective: We sought to examine the temporal trends and correlates of the availability of illicit and prescription opioids among people who inject drugs (PWID) in Vancouver, Canada., Methods: Data were derived from three prospective cohort studies of PWID in Vancouver between 2010 and 2014. In semiannual interviews, participants reported the availability of five sets of illicit and prescription opioids: (1) heroin; (2) Percocet (oxycodone/acetaminophen), Vicodin (hydrocodone/acetaminophen), or Demerol (meperidine); (3) Dilaudid (hydromorphone); (4) Morphine; (5) oxycontin/OxyNEO (controlled-release oxycodone). We defined perceived availability as immediate (e.g., available within 10 minutes) versus no availability/available after 10 minutes. The trend and correlation of immediate availability were identified by multivariable generalized estimating equations logistic regression., Results: Among 1584 participants, of which 564 (35.6%) were female, the immediate availability of all illicit and prescribed opioids (except for oxycontin/OxyNEO) increased over time, independent of potential confounders. The Adjusted Odds Ratios of immediate availability associated with every calendar year increase were between 1.09 (95% confidence interval 1.05-1.12) (morphine and Dilaudid) and 1.13 (95% confidence interval 1.09-1.17) (Percocet/Vicodin/Demerol) (all p-values <0.05)., Conclusion: The availability of most prescription opioids had continued to increase in recent years among our sample of PWID in Vancouver. Concurrent increases in the availability of heroin were also observed, raising concerns regarding combination of both illicit and prescription opioid use among PWID that could potentially increase the risk of overdose.

We estimated rates and predictors of death among a community-recruited prospective cohort of 961 human immunodeficiency virus (HIV)-infected people who inject drugs in Vancouver, Canada, between 1996 and 2014. The results demonstrated significant declines in age-adjusted all-cause and HIV-related mortality rates since 2010, coincident with the scale-up of a community-wide "seek-and-treat" campaign., (© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Socioeconomically marginalized people who use illicit drugs (PWUD) often engage in alternative income generating activities to meet their basic needs. These activities commonly carry a number of health and social risks, which may prompt some PWUD to consider addiction treatment to reduce their drug use or drug-related expenses. We sought to determine whether engaging in certain forms of income generation was independently associated with self-reported need for addiction treatment among a cohort of PWUD in Vancouver, Canada., Methods: Data from two prospective cohorts of PWUD in Vancouver were used in generalized estimating equations to identify factors associated with self-reported need for addiction treatment, with a focus on income generating activities., Results: Between June 2013 and May 2014, 1285 respondents participated in the study of whom 483 (34.1%) were female and 396 (30.8%) indicated that they needed addiction treatment. In final multivariate analyses, key factors significantly and positively associated with self-reported need for addiction treatment included engaging in illegal income generating activities (adjusted odds ratio [AOR]=1.96, 95% confidence interval [CI}: 1.11-3.46); sex work (AOR=1.61, 95% CI: 1.05-2.47), homelessness (AOR=1.65, 95% CI: 1.22-2.25); and recent engagement in counselling (AOR=1.85, 95% CI: 1.40-2.44)., Discussion: Our results suggest that key markers of socioeconomic marginalization are strongly linked with a stated need for addiction treatment. These findings underscore the need to provide appropriate and accessible addiction treatment access to marginalized PWUD and to consider alternative approaches to reduce socioeconomic disadvantage., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Illicit drug use is a well-established risk factor for increased morbidity and mortality. However, little is known about the impact of benzodiazepine use on mortality among populations of polysubstance users. This study aimed to identify the effect of benzodiazepine use on mortality among a prospective cohort of people in Canada who inject drugs (PWID)., Methods: A cohort of PWID in Vancouver, Canada, was prospectively followed from May 1996 through November 2013. Data on participants were linked to the provincial vital statistics registry to ascertain mortality rates and causes of death. Multivariable extended Cox regression with time-dependent variables was used to investigate the relationship between benzodiazepine use and time to all-cause mortality., Results: During the study period, 2,802 participants were followed for a median of 67 months (interquartile range: 25-107). In total, 527 (18.8%) participants died, for an incidence density of mortality of 2.9 (95% confidence interval [CI] 2.7, 3.2) deaths per 100 person-years. After adjusting for HIV infection and other potential confounders, benzodiazepine use was independently associated with increased all-cause mortality (adjusted hazard ratio = 1.86, 95% CI 1.38, 2.51) and had a higher risk for mortality than all other traditional substances of abuse among this population. Results were consistent when non-overdose mortality was considered., Conclusion: In this setting, benzodiazepine use was more strongly associated with mortality than any other substance of abuse. Greater recognition of the safety concerns related to benzodiazepines and strategies to prevent diversion to illicit use are needed.

Many people who inject illicit drugs receive manual assistance when injecting, and this practice has been linked to increased risk of HIV infection and other harms. Little is known, however, about this practice among youth. This study uses a multivariate generalized estimating equation to identify factors associated with receiving assistance with injecting among a cohort of street-involved youth aged 14-26 in Vancouver, Canada. A total of 253 participants reported injecting drugs during the study period, and 49 % (n = 125) of these youth reported receiving assistance with injecting in the past 6 months. In multivariate analysis, younger age, female gender, binge drug use, heroin injecting, cocaine injecting, crystal methamphetamine injecting, and syringe sharing were positively and independently associated with assisted injection (all p < 0.05). These findings underscore the need for expanding substance abuse treatment alongside HIV prevention and health promotion interventions to empower youth to enact safer injection practices.

Background: Though known to have abuse potential, benzodiazepine medications remain widely prescribed. Furthermore, issues related to benzodiazepine use by people who inject drugs (PWID) remain to be fully characterized. We therefore sought to examine the prevalence of and risk factors associated with benzodiazepine use in a street-involved urban population., Methods: Between May 1996 and November 2013, data were derived from two open prospective cohort studies in Vancouver, Canada, restricted to PWID. Multivariable logistic regression with generalized estimating equations (GEE) was used to determine factors independently associated with benzodiazepine use., Results: Over the study period, 2806 individuals were recruited, including 949 (34%) women. Of these, 1080 (38.5%) participants reported benzodiazepine use at least once during the study period. In the multivariable analysis, Caucasian ethnicity, ≥ daily heroin injection, ≥ daily cocaine injection, non-fatal overdose, incarceration, syringe sharing, and unsafe sex were all independently associated with benzodiazepine use. Conversely, older age, homelessness, and ≥ daily crack smoking were negatively associated with benzodiazepine use., Conclusions: Use of benzodiazepines was common in this urban setting and was associated with several markers of addiction severity and significant health and social vulnerabilities including syringe sharing and unsafe sex. These findings underscore the need to promote treatment for benzodiazepine use, safer benzodiazepine prescribing, including greater recognition of the limited indications for evidence-based use of this medication class., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Globally, harm reduction interventions, including needle and syringe programs (NSPs), have been shown to reduce HIV risks among people who inject drugs (PWID). However, little is known about the impact of these efforts on the circumstances of first injection. Therefore, we sought to identify changes in the awareness about HIV prevention and syringe borrowing at the time of first injection drug use in Vancouver, Canada, during a period of NSP expansion., Methods: Data were drawn from prospective cohorts of PWID in Vancouver, who initiated injecting between 1988 and 2014. Multivariable regression was used to assess changes in the awareness about HIV and NSPs and syringe borrowing behaviour at first injection against calendar year of first injection., Results: Among 1044 participants (36.9% female), at the time of first injection 73.9% reported having known syringe sharing was an HIV risk, 54.1% reported having heard of NSPs, and 7.8% reported having borrowed a syringe used by others. In multivariable analyses, calendar year of first injection was independently and positively associated with awareness about HIV (adjusted prevalence ratio [APR]: 1.09; 95% confidence interval [CI]: 1.06, 1.11) and awareness about NSPs (APR: 1.18; 95% CI: 1.13, 1.24). While calendar year of first injection was significantly and negatively associated with syringe borrowing at first injection in bivariable analyses, the association did not remain significant in multivariable analyses (adjusted odds ratio: 0.90; 95% CI: 0.72, 1.14)., Conclusions: We found that awareness about HIV and NSPs at first injection have increased over time amongst PWID in this setting. However, declining trends in syringe borrowing at first injection were not determined after adjustment for socio-demographic characteristics. This suggests that HIV prevention efforts may have contributed to increased awareness about HIV prevention, but further research is needed to identify sub-populations at heightened risk of HIV at first injection., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Although suicide is a known leading cause of death among street youth, few prospective studies have explored childhood experiences as risk factors for future suicide attempt in this population. We examined the risk of attempted suicide in relation to childhood maltreatment among street youth., Methods: From September 2005 to November 2013, data were collected from the At Risk Youth Study (ARYS), a prospective cohort of street youth in Vancouver, Canada. Inclusion criteria were age 14 to 26 years, past-month illicit drug use, and street involvement. Participants completed the Childhood Trauma Questionnaire, an instrument measuring self-reported sexual, physical, and emotional abuse and physical and emotional neglect. Suicide attempts were assessed semiannually. Using Cox regression, we examined the association between the 5 types of maltreatment and suicide attempts., Results: Of 660 participants, 68.2% were male and 24.6% were Aboriginal. Median age was 21.5 years. The prevalence of moderate to extreme childhood maltreatment ranged from 16.8% (sexual abuse) to 45.2% (emotional abuse). Participants contributed 1841 person-years, with suicide attempts reported by 35 (5.3%) individuals (crude incidence density: 1.9 per 100 person-years; 95% confidence interval [CI]: 1.4-2.6 per 100 person-years). In adjusted analyses, types of maltreatment associated with suicide attempts included physical abuse (adjusted hazard ratio [HR]: 4.47; 95% CI: 2.12-9.42), emotional abuse (adjusted HR: 4.92; 95% CI: 2.11-11.5), and emotional neglect (adjusted HR: 3.08; 95% CI: 1.05-9.03)., Conclusions: Childhood maltreatment is associated with subsequent risk of suicidal behavior among street youth. Suicide prevention efforts should be targeted toward this marginalized population and delivered from a trauma-informed perspective., (Copyright © 2015 by the American Academy of Pediatrics.)

Childhood sexual abuse is associated with adverse health outcomes. However, the impact of sexual abuse on HIV risk behaviors among people who inject drugs (IDU) has not been thoroughly characterized. We therefore sought to identify whether childhood sexual abuse was associated with syringe sharing among a sample of IDU in Vancouver, Canada. We assessed sexual abuse among two cohorts of IDUs via the Childhood Trauma Questionnaire. Multivariate logistic regression was used to estimate the relationship between childhood sexual abuse and syringe sharing. In total, 1380 IDU were included in the study, and 426 (30.9 %) IDU reported childhood sexual abuse. Syringe sharing (Adjusted Odds Ratio = 1.83, 95 % Confidence Interval 1.28-2.60) remained independently associated with childhood sexual abuse after adjustment for potential confounders. Given that a history of childhood sexual abuse appears to be elevated among IDU who engage in HIV risk behaviors (i.e., syringe sharing), HIV prevention efforts should include efforts to address historical trauma in this population.

Background: There is growing concern regarding rising rates of prescription drug-related deaths among the general North American population as well as increasing availability of illicitly obtained prescription opioids. Concurrently among people who inject drugs (IDU), illicit prescription opioid use has increased while non-fatal overdose remains a major source of morbidity., Objectives: To evaluate whether the use of prescription opioids was associated with non-fatal overdose among IDU in Vancouver, Canada., Methods: Data was obtained from two open prospective cohorts of IDU between December 2005 and May 2013. We used generalized estimating equation (GEE) logistic regression to evaluate the association between prescription opioid use and non-fatal overdose, adjusting for various social, demographic, and behavioral factors., Results: There were 1614 IDU, including 541 (33.5%) women, who were recruited and included in this analysis. At baseline, 526 (32.6%) reported using prescription opioids and 118 (7.3%) reported experiencing an overdose in the previous six months. In a multivariable analysis, prescription opioid use remained independently associated with non-fatal overdose (adjusted odds ratio: 1.61, 95% confidence interval: 1.32-1.95), after adjusting for confounders., Conclusion: We observed relatively high rates of prescription opioid use among IDU in this setting, and found an independent association between prescription opioid use and non-fatal overdose. Our data is likely representative of riskier substance use associated with those who use prescription opioids within our sample. Interventions to prevent and respond to overdoses should consider the higher risk profiles of IDU who use prescription opioids.

Introduction: While HIV/AIDS remains an important cause of death among people who inject drugs (PWID), the potential mortality burden attributable to hepatitis C virus (HCV) infection among this population is of increasing concern. Therefore, we sought to identify trends in and predictors of liver-related mortality among PWID., Methods: Data were derived from prospective cohorts of PWID in Vancouver, Canada, between 1996 and 2011. Cohort data were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. Multivariate Cox proportional hazards regression was used to examine the relationship between HCV infection and time to liver-related death. A sub-analysis examined the effect of HIV/HCV co-infection., Results and Discussion: In total, 2,279 PWID participated in this study, with 1,921 (84.3%) having seroconverted to anti-HCV prior to baseline assessments and 124 (5.4%) during follow-up. The liver-related mortality rate was 2.1 (95% confidence interval [CI]: 1.5-3.0) deaths per 1,000 person-years and was stable over time. In multivariate analyses, HCV seropositivity was not significantly associated with liver-related mortality (adjusted relative hazard [ARH]: 0.45; 95% CI: 0.15-1.37), but HIV seropositivity was (ARH: 2.67; 95% CI: 1.27-5.63). In sub-analysis, HIV/HCV co-infection had a 2.53 (95% CI: 1.18-5.46) times hazard of liver-related death compared with HCV mono-infection., Conclusions: In this study, HCV seropositivity did not predict liver-related mortality while HIV seropositivity did. The findings highlight the critical role of HIV mono- and co-infection rather than HCV infection in contributing to liver-related mortality among PWID in this setting.

Background: Microarray normalizations typically apply methods that assume absence of global transcript shifts, or absence of changes in internal control features such as housekeeping genes. These normalization approaches are not appropriate for focused arrays with small sets of genes where a large portion may be expected to change. Furthermore, many microarrays lack control features that can be used for quality assurance (QA). Here, we describe a novel external control series integrated with a design feature that addresses the above issues., Results: An EC dilution series that involves spike-in of a single concentration of the A. thaliana chlorophyll synthase gene to hybridize against spotted dilutions (0.000015 to 100 microM) of a single complimentary oligonucleotide representing the gene was developed. The EC series is printed in duplicate within each subgrid of the microarray and covers the full range of signal intensities from background to saturation. The design and placement of the series allows for QA examination of frequently encountered problems in hybridization (e.g., uneven hybridizations) and printing (e.g., cross-spot contamination). Additionally, we demonstrate that the series can be integrated with a LOWESS normalization to improve the detection of differential gene expression (improved sensitivity and predictivity) over LOWESS normalization on its own., Conclusion: The quality of microarray experiments and the normalization methods used affect the ability to measure accurate changes in gene expression. Novel methods are required for normalization of small focused microarrays, and for incorporating measures of performance and quality. We demonstrate that dilution of oligonucleotides on the microarray itself provides an innovative approach allowing the full dynamic range of the scanner to be covered with a single gene spike-in. The dilution series can be used in a composite normalization to improve detection of differential gene expression and to provide quality control measures.