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Background and Objectives: While methadone is well established as an evidence-based treatment for opioid use disorder, safety concerns persist regarding its diversion. The authors examine the prevalence of and risk factors associated with injection of methadone in an urban population., Methods: Between December 2005 and November 2013, data were derived from two open prospective studies of persons who inject drugs (PWID) in Vancouver, Canada. Generalized estimating equations (GEE) logistic regression was used to determine factors independently associated with illicit methadone injecting., Results: During the study, 1911 individuals (34% women) were recruited; 134 (7%) participants reported methadone injecting at least once. In multivariable analysis, Caucasian ethnicity [adjusted odds ratio (AOR) = 1.90, 95% confidence interval (CI) = 1.20-3.00]; homelessness (AOR = 1.46, 95% CI = 1.09-1.95); drug dealing (AOR = 2.10, 95% CI = 1.50-2.93); ≥daily heroin injection (AOR = 1.57, 95% CI = 1.08-2.26); ≥daily crack smoking (AOR = 2.06, 95% CI = 1.44-2.95); being a victim of violence (AOR = 1.48, 95% CI = 1.04-2.12); and non-fatal overdose (AOR = 1.67, 95% CI = 1.67 (1.00-2.79) were independently and positively associated with methadone injection; female gender (AOR = 0.47, 95% CI = 0.30-0.75) was negatively associated., Discussion and Conclusions: The diversion of methadone for illicit injection in this urban setting was associated with several markers of addiction severity and other health and social vulnerabilities., Scientific Significance: These findings underscore the need to ensure methadone accessibility while limiting diversion-related risk., (© American Academy of Addiction Psychiatry.)

Introduction and Aims: Methadone maintenance therapy (MMT) is an evidence-based treatment for opioid addiction. While gender differences in MMT pharmacokinetics, drug use patterns and clinical profiles have been previously described, few studies have compared rates of MMT use among community-recruited samples of persons who inject drugs (PWID)., Design and Methods: The present study used prospective cohorts of PWID followed between May 1996 and May 2013 in Vancouver, British Columbia, Canada. We investigated potential factors associated with time to methadone initiation using Cox proportional hazards modelling. Stratified analyses were used to examine for gender differences in rates of MMT enrolment., Results: Overall, 1848 baseline methadone-naïve PWID were included in the study, among whom 595 (32%) were female. In an adjusted model, male gender was independently associated with increased time to MMT initiation and an overall lower rate of enrolment [adjusted relative hazard = 0.74 (95% confidence interval: 0.65-0.85)]. Among both female and male PWID, Caucasian ethnicity and daily injection heroin use were associated with decreased time to methadone initiation, while in females, pregnancy was also associated with more rapid initiation., Discussion and Conclusions: These data highlight gender differences in methadone use among a population of community-recruited PWID. While factors associated with methadone use were similar between genders, rates of use were lower among male PWID, highlighting the need to consider gender when designing strategies to improve recruitment into MMT. [Bach P, Milloy M-J, Nguyen P, Koehn J, Guillemi S, Kerr T, Wood E. Gender differences in access to methadone maintenance therapy in a Canadian setting. Drug Alcohol Rev 2015;34:503-7]., (© 2015 Australasian Professional Society on Alcohol and other Drugs.)

The complexity of treating concurrent pain and opioid dependence among many methadone-maintained individuals presents a major challenge in many clinical settings. Furthermore, recent expert guidelines have called for increased research on the safety of methadone in the context of chronic pain. This study explores the prevalence and correlates of pain among a prospective cohort of people who use illicit drugs in Vancouver, British Columbia, Canada, who reported enrollment in methadone maintenance treatment (MMT) between 2011 and 2014. Among the 823 participants eligible for this analysis, 338 (40.9%) reported moderate pain and 91 (11.1%) reported extreme pain at the first study visit. In multivariable, generalized, linear mixed model analyses, higher pain severity was positively and independently associated with self-managing pain (adjusted odds ratio [AOR] 2.15, 95% confidence interval [CI] 1.77-2.60), patient perception of methadone dose being too low (AOR 1.82, 95% CI 1.41-2.34), older age (AOR 1.31, 95% CI 1.13-1.51), having a physical disability (AOR 4.59, 95% CI 3.73-5.64), having ever been diagnosed with a mental illness (AOR 1.44, 95% CI 1.13-1.84), white ethnicity (AOR 1.42, 95% CI 1.10-1.83), and marijuana use (AOR 1.25, 95% CI 1.02-1.52). These findings suggest several areas for clinical intervention, particularly related to patient education and alternative analgesic approaches for MMT patients experiencing pain. Perspective: To better understand the complexity of concurrent pain and opioid dependency among individuals on methadone maintenance treatment, this article describes the prevalence and correlates of higher pain severity among methadone-maintained people who use illicit drugs. Patients on methadone with comorbid pain may benefit from education and alternative analgesic approaches., (Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background and Aims: For HIV-positive individuals who use illicit opioids, engagement in methadone maintenance therapy (MMT) can contribute to improved HIV treatment outcomes. However, to our knowledge, the role of methadone dosing in adherence to antiretroviral therapy (ART) has not yet been investigated. We sought to examine the relationship between methadone dose and ART adherence among a cohort of people who use illicit opioids., Design and Setting: We used data from the AIDS Care Cohort to Evaluate Access to Survival Services (ACCESS) study, an ongoing prospective observational cohort of HIV-positive people who use illicit drugs in Vancouver, Canada, linked confidentially to comprehensive HIV treatment data in a setting of universal no-cost medical care, including medications. We evaluated the longitudinal relationship between methadone dose and the likelihood of ≥ 95% adherence to ART among ART-exposed participants during periods of engagement in MMT., Participants: Two hundred and ninety-seven ART-exposed individuals on MMT were recruited between December 2005 and May 2013 and followed for a median of 42.1 months., Measurements: We measured methadone dose at ≥ 100 versus < 100 mg/day and the likelihood of ≥ 95% adherence to ART., Findings: In adjusted generalized estimating equation (GEE) analyses, MMT dose ≥ 100 mg/day was associated independently with optimal adherence to ART [adjusted odds ratio (AOR) = 1.38; 95% confidence interval (CI) = 1.08-1.77). In a subanalysis, we observed a dose-response relationship between increasing MMT dose and ART adherence (AOR = 1.06 per 20 mg/day increase, 95% CI = 1.00-1.12)., Conclusion: Among HIV-positive individuals in methadone maintenance therapy, those receiving higher doses of methadone (≥ 100 mg/day) are more likely to achieve ≥ 95% adherence to antiretroviral therapy than those receiving lower doses., (© 2015 Society for the Study of Addiction.)

Background: Despite barriers to its use in many settings, opioid agonist therapy with methadone has become the standard of care for treating opioid (e.g. heroin) use disorder. Since people with opioid use disorders have an increased incidence of incarceration, we undertook the present study to evaluate the association between incarceration and methadone maintenance therapy among a cohort of injection drug users in a Canadian setting., Methods: A cohort of people who inject drugs was prospectively followed between May 1996 and May 2013 in Vancouver, Canada. We investigated the relationship between recent incarceration and methadone use using multivariate generalized estimating equation (GEE) logistic regression analysis., Results: Overall, 2758 individuals were recruited during the study period and followed for a median of 64 (interquartile range: 23-106) months. After adjusting for various potential confounders in the multivariate GEE model, being incarcerated remained independently associated with a lower likelihood of having received methadone treatment (Adjusted Odds Ratio: 0.87, 95% confidence interval: 0.81-0.93)., Conclusions: Our study demonstrates that incarceration was independently associated with a significantly lower likelihood of being on methadone. Given the role of methadone in reducing the harms of heroin use, including drug acquisitive crime and recidivism, these data suggest a need to scale-up methadone provision for incarcerated injection drug users., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Many people who use illicit drugs (PWUD) face challenges to their financial stability. Resulting activities that PWUD undertake to generate income may increase their vulnerability to violence. We therefore examined the relationship between income generation and exposure to violence across a wide range of income generating activities among HIV-positive and HIV-negative PWUD living in Vancouver, Canada., Methods: Data were derived from cohorts of HIV-seropositive and HIV-seronegative PWUD (n=1876) between December 2005 and November 2012. We estimated the relationship between different types of income generation and suffering physical or sexual violence using bivariate and multivariate generalised estimating equations, as well as the characteristics of violent interactions., Results: Exposure to violence was reported among 977 (52%) study participants over the study period. In multivariate models controlling for sociodemographic characteristics, mental health status, and drug use patterns, violence was independently and positively associated with participation in street-based income generation activities (ie, recycling, squeegeeing and panhandling; adjusted OR (AOR)=1.39, 95% CI 1.23 to 1.57), sex work (AOR=1.23, 95% CI 1.00 to 1.50), drug dealing (AOR=1.63, 95% CI 1.44 to 1.84), and theft and other acquisitive criminal activity (AOR=1.51, 95% CI 1.27 to 1.80). Engagement in regular, self-employment or temporary employment was not associated with being exposed to violence. Strangers were the most common perpetrators of violence (46.7%) and beatings the most common type of exposure (70.8%)., Conclusions: These results suggest that economic activities expose individuals to contexts associated with social and structural vulnerability to violence. The creation of safe economic opportunities which can minimise vulnerability to violence among PWUD is therefore urgently required., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Among prospective cohorts of people who inject drugs (PWID), phylogenetic clustering of HCV infection has been observed. However, the majority of studies have included older PWID, representing distant transmission events. The aim of this study was to investigate phylogenetic clustering of HCV infection among a cohort of street-involved youth., Methods: Data were derived from a prospective cohort of street-involved youth aged 14-26 recruited between 2005 and 2012 in Vancouver, Canada (At Risk Youth Study, ARYS). HCV RNA testing and sequencing (Core-E2) were performed on HCV positive participants. Phylogenetic trees were inferred using maximum likelihood methods and clusters were identified using ClusterPicker (Core-E2 without HVR1, 90% bootstrap threshold, 0.05 genetic distance threshold)., Results: Among 945 individuals enrolled in ARYS, 16% (n=149, 100% recent injectors) were HCV antibody positive at baseline interview (n=86) or seroconverted during follow-up (n=63). Among HCV antibody positive participants with available samples (n=131), 75% (n=98) had detectable HCV RNA and 66% (n=65, mean age 23, 58% with recent methamphetamine injection, 31% female, 3% HIV+) had available Core-E2 sequences. Of those with Core-E2 sequence, 14% (n=9) were in a cluster (one cluster of three) or pair (two pairs), with all reporting recent methamphetamine injection. Recent methamphetamine injection was associated with membership in a cluster or pair (P=0.009)., Conclusion: In this study of street-involved youth with HCV infection and recent injecting, 14% demonstrated phylogenetic clustering. Phylogenetic clustering was associated with recent methamphetamine injection, suggesting that methamphetamine drug injection may play an important role in networks of HCV transmission., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background and Objectives: Although new medications are needed to address the harms of drug addiction, rates of willingness to participate in addiction treatment trials among people who use drugs (PWUD), have not been well characterized., Methods: One thousand twenty PWUD enrolled in two community-recruited cohorts in Vancouver, Canada, were asked whether they would be willing to participate in a pharmacologic addiction treatment trial. Logistic regression was used to identify factors independently associated with a willingness to participate., Results: Among the 1,020 PWUD surveyed between June 1, 2013 and November 30, 2013, 58.3% indicated a willingness to participate. In multivariate analysis, factors independently associated with a willingness to participate in a pharmacologic addiction treatment trial included: daily heroin injection (Adjusted Odds Ratio [AOR] = 1.75; 95% Confidence Interval [CI]: 1.13 - 2.72); daily crack smoking (AOR = 1.81; 95% CI: 1.23 - 2.66); sex work involvement (AOR = 2.22; 95% CI: 1.21 - 4.06); HIV seropositivity (AOR = 1.49; 95% CI: 1.15 - 1.94); and methadone maintenance therapy participation (AOR = 1.77; 95% CI: 1.37-2.30)., Discussion and Conclusions: High rates of willingness to participate in a pharmacologic addiction treatment trial were observed in this setting. Importantly, high-risk drug and sexual activities were positively associated with a willingness to participate, which may suggest a desire for new treatment interventions among PWUD engaged in high-risk behavior., Scientific Significance: These results highlight the viability of studies seeking to enroll representative samples of PWUD engaged in high-risk drug use., (© American Academy of Addiction Psychiatry.)

Background: People who inject drugs (PWID) account for roughly 13% of the prevalent HIV/AIDS population outside of sub-Saharan Africa, and access to opioid substitution treatment (OST) is limited in many settings globally. OST likely facilitates access to HAART, yet sparse evidence is available to support this hypothesis. Our objective was to determine the causal impact of OST exposure on HAART adherence among HIV-positive PWID in a Canadian setting., Methods: We executed a retrospective cohort study using linked population-level data for British Columbia, Canada (January 1996-March 2010). We considered HIV-positive PWID after meeting HAART initiation criteria. A marginal structural model was estimated on a monthly timescale using inverse probability of treatment weights. The primary outcome was 95% HAART adherence, according to pharmacy refill compliance. Exposure to OST was defined as 95% of OST receipt, and we controlled for a range of fixed and time-varying covariates., Results: Our study included 1852 (63.3%) HIV-positive PWID with a median follow-up of 5.5 years; 34% were female and 39% had previously accessed OST. The baseline covariate-adjusted odds of HAART adherence following OST exposure was 1.96 (95% confidence interval: 1.72-2.24), although the adjusted odds estimated within the marginal structural model was 1.68 (1.48-1.92). Findings were robust to sensitivity analyses on model specification., Conclusion: In a setting characterized by universal healthcare and widespread access to both office-based OST and HAART, OST substantially increased the odds of HAART adherence. This underlines the need to address barriers to OST globally to reduce the disease burden of both opioid dependence and HIV/AIDS.

Background: Although opioid-agonist therapy with methadone or buprenorphine/naloxone is currently the mainstay of medical treatment for opioid use disorder, these medications often are not well accepted or tolerated by patients. Recently, extended release naltrexone (XR-NTX), an opioid antagonist, has been advanced as an alternative treatment. The willingness of opioid-addicted patients to take XR-NTX has not been well described., Methods: Opioid-using persons enrolled in a community-recruited cohort in Vancouver, Canada, were asked whether or not they would be willing to take XR-NTX. Logistic regression was used to independently identify factors associated with willingness to take the medication., Results: Among the 657 participants surveyed between June 1, 2013, and November 30, 2013, 342 (52.1%) were willing to take XR-NTX. One factor positively associated with willingness was daily heroin injection (adjusted odds ratio [AOR] = 1.53; 95% confidence interval [CI] = 1.02-2.31), whereas Caucasian ethnicity was negatively associated (AOR = 0.59; 95% CI = 0.43-0.82). Satisfaction with agonist therapy (13.4%) and unwillingness to stop opioids being used for pain (26.9%) were the most common reasons for being unwilling to take XR-NTX., Conclusions: A high level of willingness to take XR-NTX was observed in this setting. Interestingly, daily injection heroin use was positively associated with willingness, whereas Caucasian participants were less willing to take XR-NTX. Although explanations for unwillingness were described in this study, further research is needed to investigate real-world acceptability of XR-NTX as an additional option for the treatment of opioid use disorder.

While regulatory frameworks governing methadone maintenance therapy (MMT) require highly regimented treatment programs that shape treatment outcomes, little research has examined the effects of regulatory changes to these programs on those receiving treatment, and located their experiences within the wider context of social-structural inequities. In British Columbia (BC), Canada, provincial regulations governing MMT have recently been modified, including: replacing the existing methadone formulation with Methadose(®) (pre-mixed and 10 times more concentrated); prohibiting pharmacy delivery of methadone; and, prohibiting pharmacies incentives for methadone dispensation. We undertook this study to examine the impacts of these changes on a structurally vulnerable population enrolled in MMT in Vancouver, BC. Qualitative interviews were conducted with 34 people enrolled in MMT and recruited from two ongoing observational prospective cohort studies comprised of drug-using individuals in the six-month period in 2014 following these regulatory changes. Interview transcripts were analysed thematically, and by drawing on the concept of 'structural vulnerability'. Findings underscore how these regulatory changes disrupted treatment engagement, producing considerable health and social harms. The introduction of Methadose(®) precipitated increased withdrawal symptoms. The discontinuation of pharmacy delivery services led to interruptions in MMT and co-dispensed HIV medications due to constraints stemming from their structural vulnerability (e.g., poverty, homelessness). Meanwhile, the loss of pharmacy incentives limited access to material supports utilized by participants to overcome barriers to MMT, while diminishing their capacity to assert some degree of agency in negotiating dispensation arrangements with pharmacies. Collectively, these changes functioned to compromise MMT engagement and increased structural vulnerability to harm, including re-initiation of injection drug use and participation in high-risk income-generating strategies. Greater attention to the impacts of social-structural inequities on MMT engagement is needed when modifying MMT programs, especially as other jurisdictions are adopting similar changes. Comprehensive environmental supports should be provided to minimize adverse outcomes during transitional periods., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Among people living with HIV/AIDS, illicit drug use is a risk for sub-optimal treatment outcomes. However, few studies have examined the relative contributions of different patterns of drug use on adherence to antiretroviral therapy (ART). We sought to estimate the effect of different types of illicit drug use on adherence in a setting of universal free HIV/AIDS treatment and care., Methods: Using data from ongoing prospective cohorts of HIV-positive illicit drug users linked to comprehensive pharmacy dispensation records in Vancouver, Canada, we examined factors associated with ≥95% prescription refill adherence using generalized estimating equations (GEE) logistic regression., Results: Between 1996 and 2013, 692 ART-exposed individuals were followed for a median of 42.7 months (Interquartile Range: 29.1-71.7). In multivariable GEE analyses, heroin injection (Adjusted Odds Ratio [AOR] = 0.75, 95% Confidence Interval [CI]: 0.66-0.85) as well as cocaine injection (AOR = 0.80, 95% CI: 0.72-0.90) were associated with lower likelihoods of optimal adherence. Methadone maintenance therapy (AOR = 1.88, 95% CI: 1.68-2.11) was associated with a greater likelihood of adherence., Conclusions: Periods of heroin and cocaine injection appeared to have the most deleterious impact upon antiretroviral adherence. The findings point to the need for improved access to treatment for heroin use disorder, particularly methadone, and highlight the need to identify strategies to support ART adherence among cocaine injectors.

Introduction: Although people who inject drugs (IDU) remain at a high risk of accidental overdose, interventions that address overdose remain limited. Accordingly there is a continuing need to identify psychological and social factors that shape overdose risk. Despite being reported frequently among IDU, childhood trauma has received little attention as a potential risk factor for overdose. This study aims to evaluate relationships between non-fatal overdose and five forms of childhood maltreatment among a cohort of IDU in Vancouver, Canada., Methods: Data was obtained from two prospective cohorts of IDU between December 2005 and May 2013. Multivariate generalized estimating equations (GEEs) were used to explore relationships between five forms of childhood trauma and non-fatal overdose, adjusting for potential confounders., Results: During the study period, 1697 IDU, including 552 (32.5%) women, were followed up. At baseline, 1136 (67.0%) participants reported at least one form of childhood trauma, while 4-9% reported a non-fatal overdose at each semi-annual follow-up. In multivariate analyses, physical [adjusted odds ratio (AOR): 1.36, 95% confidence interval (CI): 1.08-1.71], sexual (AOR: 1.48, CI: 1.17-1.87), and emotional abuse (AOR: 1.54, CI: 1.22-1.93) and physical neglect (AOR: 1.28, CI: 1.01-1.62) were independently associated with non-fatal overdose (all p<0.05)., Conclusions: Childhood trauma was common among participants, and reporting an experience of trauma was positively associated with non-fatal overdose. These findings highlight the need to provide intensive overdose prevention to trauma survivors and to incorporate screening for childhood trauma into health and social programs tailored to IDU., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction and Aims: Cannabis use is common among people who are living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). While there is growing pre-clinical evidence of the immunomodulatory and anti-viral effects of cannabinoids, their possible effects on HIV disease parameters in humans are largely unknown. Thus, we sought to investigate the possible effects of cannabis use on plasma HIV-1 RNA viral loads (pVLs) among recently seroconverted illicit drug users., Design and Methods: We used data from two linked longitudinal observational cohorts of people who use injection drugs. Using multivariable linear mixed-effects modelling, we analysed the relationship between pVL and high-intensity cannabis use among participants who seroconverted following recruitment., Results: Between May 1996 and March 2012, 88 individuals seroconverted after recruitment and were included in these analyses. Median pVL in the first 365 days among all seroconverters was 4.66 log10 c mL(-1) . In a multivariable model, at least daily cannabis use was associated with 0.51 log10 c mL(-1) lower pVL (β = -0.51, standard error = 0.170, P value = 0.003)., Discussion and Conclusions: Consistent with the findings from recent in vitro and in vivo studies, including one conducted among lentiviral-infected primates, we observed a strong association between cannabis use and lower pVL following seroconversion among illicit drug-using participants. Our findings support the further investigation of the immunomodulatory or antiviral effects of cannabinoids among individuals living with HIV/AIDS., (© 2014 Australasian Professional Society on Alcohol and other Drugs.)

Background: Illicit drug injecting is a well-established risk factor for morbidity and mortality. However, a limited number of prospective studies have examined the independent effect of unstable housing on mortality among persons who inject drugs (PWIDs). In this study we sought to identify if a relationship exists between unstable housing and all-cause mortality among PWIDs living in Vancouver, Canada., Methods: PWIDs participating in two prospective cohort studies in Vancouver, Canada were followed between May 1996 and December 2012. Cohort data were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. We used multivariate Cox proportional hazards regression to determine factors associated with all-cause mortality and to investigate the independent relationship between unstable housing and time to all-cause mortality., Results: During the study period, 2453 individuals were followed for a median of 69 months (Inter-quartile range [IQR]: 34 - 113). In total, there were 515 (21.0%) deaths for an incidence density of 3.1 (95% Confidence Interval [CI]: 2.8 - 3.4) deaths per 100 person years. In multivariate analyses, after adjusting for potential confounders including HIV infection and drug use patterns, unstable housing remained independently associated with all-cause mortality (adjusted hazard ratio [AHR] = 1.30, 95% CI: 1.08 - 1.56)., Conclusions: These findings demonstrate that unstable housing is an important risk factor for mortality independent of known risk factors including HIV infection and patterns of drug use. This study highlights the urgent need to provide supportive housing interventions to address elevated levels of preventable mortality among this population.

Cannabis is increasingly prescribed clinically and utilized by people living with HIV/AIDS (PLWHA) to address symptoms of HIV disease and to manage side effects of antiretroviral therapy (ART). In light of concerns about the possibly deleterious effect of psychoactive drug use on adherence to ART, we sought to determine the relationship between high-intensity cannabis use and adherence to ART among a community-recruited cohort of HIV-positive illicit drug users. We used data from the ACCESS study, an ongoing prospective cohort study of HIV-seropositive illicit drug users linked to comprehensive ART dispensation records in a setting of universal no-cost HIV care. We estimated the relationship between at least daily cannabis use in the last 6 months, measured longitudinally, and the likelihood of optimal adherence to ART during the same period, using a multivariate linear mixed-effects model accounting for relevant socio-demographic, behavioral, clinical and structural factors. From May 2005 to May 2012, 523 HIV-positive illicit drug users were recruited and contributed 2,430 interviews. At baseline, 121 (23.1 %) participants reported at least daily cannabis use. In bivariate and multivariate analyses we did not observe an association between using cannabis at least daily and optimal adherence to prescribed HAART (Adjusted Odds Ratio = 1.12, 95 % Confidence Interval [95 % CI]: 0.76-1.64, p value = 0.555.) High-intensity cannabis use was not associated with adherence to ART. These findings suggest cannabis may be utilized by PLWHA for medicinal and recreational purposes without compromising effective adherence to ART.

Aims: To determine the impact of HIV infection on mortality over time among people who inject drugs (PWID) in settings with free HIV/AIDS care., Design and Setting: Prospective cohort study of PWID in Vancouver, Canada, recruited between May 1996 and December 2011. We ascertained morality rates and causes of death through a confidential linkage with the provincial vital statistics registry., Participants: A total of 2283 individuals were followed for a median of 60.9 months (interquartile range: 34.4-113.1), among whom 622 (27.2%) individuals were HIV-positive at baseline, and 179 (7.8%) seroconverted during follow-up., Measurements: The primary and secondary outcomes of interests were all-cause mortality and cause of death, respectively. The main independent variable of interest was HIV serostatus (positive versus negative). We used Cox proportional hazards regression to determine factors associated with mortality, including socio-demographic variables, drug use behaviors and other risk behaviors., Findings: During the study period, 491 (21.5%) individuals died. In multivariate analyses, HIV infection remained associated independently with all-cause mortality (adjusted hazard ratio = 3.15; 95% CI: 2.59-3.82). While all-cause mortality rates declined markedly during the study period (P < 0.001), the independent effect of HIV infection on mortality remained unchanged over time (P = 0.640). Among HIV-positive individuals, significant changes in causes of death from infectious and AIDS-related causes to non-AIDS-related etiologies were observed., Conclusions: HIV infection continues to have a persistent impact on mortality rates among people who inject drugs in settings with free HIV/AIDS care, although causes of death have shifted markedly from infectious and AIDS-related causes to non-AIDS-related etiologies., (© 2014 Society for the Study of Addiction.)

HIV-positive people who use illicit drugs typically achieve lower levels of adherence to antiretroviral therapy and experience higher rates of sub-optimal HIV/AIDS treatment outcomes. Given the dearth of longitudinal research into ART adherence dynamics, we sought to identify factors associated with transitioning into and out of optimal adherence to ART in a longitudinal study of HIV-infected people who use illicit drugs (PWUD) in a setting of universal no-cost HIV/AIDS treatment. Using data from a prospective cohort of community-recruited HIV-positive illicit drug users confidentially linked to comprehensive HIV/AIDS treatment records, we estimated longitudinal factors associated with losing or gaining ≥95% adherence in the previous six months using two generalized linear mixed-effects models. Among 703 HIV-infected ART-exposed PWUD, becoming non-adherent was associated with periods of homelessness (adjusted odds ratio [AOR] = 2.52, 95% confidence interval [95% CI]: 1.56-4.07), active injection drug use (AOR = 1.25, 95% CI: 1.01-1.56) and incarceration (AOR = 1.54, 95% CI: 1.10-2.17). Periods of sex work (AOR = 0.51, 95% CI: 0.34-0.75) and injection drug use (AOR = 0.62, 95% CI: 0.50-0.77) were barriers to becoming optimally adherent. Methadone maintenance therapy was associated with becoming optimally adherent (AOR = 1.87, 95% CI: 1.50-2.33) and was protective against becoming non-adherent (AOR = 0.52, 95% CI: 0.41-0.65). In conclusion, we identified several behavioural, social and structural factors that shape adherence patterns among PWUD. Our findings highlight the need to consider these contextual factors in interventions that support the effective delivery of ART to this population.

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: Illicit drug use is a well-established risk factor for morbidity and mortality. However, few studies have examined the impact of different drug use patterns on mortality among polysubstance using populations. This study aimed to identify drug-specific patterns of mortality among a cohort of polysubstance using persons who inject drugs (PWIDs)., Methods: PWIDs in Vancouver, Canada were prospectively followed between May 1996 and December 2011. Participants were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. We used multivariate Cox proportional hazards regression to investigate the relationships between drug use patterns (daily alcohol use, heroin injection and non-injection use, cocaine injection, amphetamine injection and non-injection use, crack smoking and speedball injecting) and time to all-cause mortality., Results: 2330 individuals were followed for a median of 61 months (inter-quartile range: 33 - 112). In total, 466 (19.1%) individuals died for an incidence density of 3.1 (95% confidence interval [CI]: 2.8 - 3.4) deaths per 100 person-years. In multivariate analyses, after adjusting for HIV infection and other potential confounders, only daily cocaine injection remained independently associated with all-cause mortality (adjusted hazard ratio [AHR] = 1.36, 95% CI: 1.06 - 1.76)., Conclusions: Although heroin injecting is traditionally viewed as carrying the highest risk of mortality, in this setting, only daily cocaine injecting was associated with all-cause mortality. These findings highlight the urgent need to identify novel treatments and harm reduction strategies for cocaine injectors.

Unlabelled: Little is known about factors associated with hepatitis C virus (HCV) transmission among people who inject drugs (PWID). Phylogenetic clustering and associated factors were evaluated among PWID in Vancouver, Canada. Data were derived from the Vancouver Injection Drug Users Study. Participants who were HCV antibody-positive at enrolment and those with HCV antibody seroconversion during follow-up (1996 to 2012) were tested for HCV RNA and sequenced (Core-E2 region). Phylogenetic trees were inferred using maximum likelihood analysis and clusters were identified using ClusterPicker (90% bootstrap threshold, 0.05 genetic distance threshold). Factors associated with clustering were assessed using logistic regression. Among 655 eligible participants, HCV genotype prevalence was: G1a: 48% (n=313), G1b: 6% (n=41), G2a: 3% (n=20), G2b: 7% (n=46), G3a: 33% (n=213), G4a: <1% (n=4), G6a: 1% (n=8), G6e: <1% (n=1), and unclassifiable: 1% (n=9). The mean age was 36 years, 162 (25%) were female, and 164 (25%) were HIV+. Among 501 participants with HCV G1a and G3a, 31% (n=156) were in a pair/cluster. Factors independently associated with phylogenetic clustering included: age <40 (versus age≥40, adjusted odds ratio [AOR]=1.64; 95% confidence interval [CI] 1.03, 2.63), human immunodeficiency virus (HIV) infection (AOR=1.82; 95% CI 1.18, 2.81), HCV seroconversion (AOR=3.05; 95% CI 1.40, 6.66), and recent syringe borrowing (AOR 1.59; 95% CI 1.07, 2.36)., Conclusion: In this sample of PWID, one-third demonstrated phylogenetic clustering. Factors independently associated with phylogenetic clustering included younger age, recent HCV seroconversion, prevalent HIV infection, and recent syringe borrowing. Strategies to enhance the delivery of prevention and/or treatment strategies to those with HIV and recent HCV seroconversion should be explored, given an increased likelihood of HCV transmission in these subpopulations., (© 2014 by the American Association for the Study of Liver Diseases.)

Contact with the criminal justice system, including incarceration, is a common experience for many people living with HIV/AIDS. Optimism has recently been expressed that correctional facilities could be important locations for treatment-as-prevention (TasP)-based initiatives. We review recent findings regarding the effect of incarceration on patterns of HIV transmission, testing, treatment initiation and retention. We found that the prevalence of HIV infection among incarcerated individuals remains higher than analogous non-incarcerated populations. Recent studies have shown that voluntary HIV/AIDS testing is feasible in many correctional facilities, although the number of previously undiagnosed individuals identified has been modest. Studies have implied enhanced linkage to HIV/AIDS treatment and care in jails in the United States was associated with improvements in the HIV cascade of care. However, for many individuals living with HIV/AIDS, exposure to the correctional system remains an important barrier to retention in HIV/AIDS treatment and care. Future research should evaluate structural interventions to address these barriers and facilitate the scale-up of TasP-based efforts among individuals living in correctional settings.

Background: The reproducible nature of HIV-1 escape from HLA-restricted CD8+ T-cell responses allows the identification of HLA-associated viral polymorphisms "at the population level" - that is, via analysis of cross-sectional, linked HLA/HIV-1 genotypes by statistical association. However, elucidating their timing of selection traditionally requires detailed longitudinal studies, which are challenging to undertake on a large scale. We investigate whether the extent and relative timecourse of immune-driven HIV adaptation can be inferred via comparative cross-sectional analysis of independent early and chronic infection cohorts., Results: Similarly-powered datasets of linked HLA/HIV-1 genotypes from individuals with early (median < 3 months) and chronic untreated HIV-1 subtype B infection, matched for size (N > 200/dataset), HLA class I and HIV-1 Gag/Pol/Nef diversity, were established. These datasets were first used to define a list of 162 known HLA-associated polymorphisms detectable at the population level in cohorts of the present size and host/viral genetic composition. Of these 162 known HLA-associated polymorphisms, 15% (occurring at 14 Gag, Pol and Nef codons) were already detectable via statistical association in the early infection dataset at p ≤ 0.01 (q < 0.2) - identifying them as the most consistently rapidly escaping sites in HIV-1. Among these were known rapidly-escaping sites (e.g. B*57-Gag-T242N) and others not previously appreciated to be reproducibly rapidly selected (e.g. A*31:01-associated adaptations at Gag codons 397, 401 and 403). Escape prevalence in early infection correlated strongly with first-year escape rates (Pearson's R = 0.68, p = 0.0001), supporting cross-sectional parameters as reliable indicators of longitudinally-derived measures. Comparative analysis of early and chronic datasets revealed that, on average, the prevalence of HLA-associated polymorphisms more than doubles between these two infection stages in persons harboring the relevant HLA (p < 0.0001, consistent with frequent and reproducible escape), but remains relatively stable in persons lacking the HLA (p = 0.15, consistent with slow reversion). Published HLA-specific Hazard Ratios for progression to AIDS correlated positively with average escape prevalence in early infection (Pearson's R = 0.53, p = 0.028), consistent with high early within-host HIV-1 adaptation (via rapid escape and/or frequent polymorphism transmission) as a correlate of progression., Conclusion: Cross-sectional host/viral genotype datasets represent an underutilized resource to identify reproducible early pathways of HIV-1 adaptation and identify correlates of protective immunity.

Objective: Studies have demonstrated the central function of plasma HIV-1 RNA viral load (pVL) levels on determining the risk of HIV disease progression and transmission. However, there is limited empirical research on virologic outcomes among sex workers who use illicit drugs (SW-DU)., Methods: Data were derived from the AIDS Care Cohort to evaluate Exposure to Survival Services, a cohort of HIV-positive illicit drug users. Using generalised estimating equations, we studied the longitudinal relationship between sex work and pVL suppression. We also tested whether adherence to antiretroviral therapy (ART) mediated the relationship between sex work and pVL suppression., Results: Between May 1996 and May 2012, 587 ART-exposed participants (2224 person-years of observation) were included in the study, among whom 127 (21.6%) reported sex work. In a time-updated multivariate model adjusted for various demographic, socioeconomic and clinical confounders (eg, gender, incarceration, CD4 cell count), SW-DU had an independently reduced odds of pVL suppression compared to non-SW-DU (adjusted OR (AOR)=0.66; 95% CI 0.45 to 0.96). However, adding ART adherence to the multivariate model eliminated this association (p>0.05), suggesting adherence mediated the relationship between sex work and pVL suppression., Conclusions: Evidence-based interventions to improve adherence to ART among SW-DU are urgently needed to help produce the maximum HIV treatment and prevention benefit of ART among this highly vulnerable population., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: People who inject drugs (PWID) are at high risk of hepatitis C virus (HCV) infection. Trends in HCV incidence and associated risk factors among PWID recruited between 1996 and 2012 in Vancouver, Canada were evaluated., Methods: Data were derived from a long-term cohort of PWID in Vancouver. Trends in HCV incidence were evaluated. Factors associated with time to HCV infection were assessed using Cox proportional hazards regression., Results: Among 2,589, 82% (n = 2,121) were HCV antibody-positive at enrollment. Among 364 HCV antibody-negative participants with recent (last 30 days) injecting at enrollment, 126 HCV seroconversions were observed [Overall HCV incidence density: 8.6 cases/100 person-years (py); 95% confidence interval (95% CI): 7.2, 10.1; HCV incidence density among those with injecting during follow-up: 11.5 cases/100 py; 95% CI 9.7, 13.6]. The overall HCV incidence density declined significantly from 25.0/100 py (95% CI: 20.2, 30.3) in 1996-99, as compared to 6.0/100 py (95% CI: 4.1, 8.5) in 2000-2005, and 3.1/100 py (95% CI: 2.0, 4.8) in 2006-2012. Among those with injecting during follow-up, the overall HCV incidence density declined significantly from 27.9/100 py (95% CI: 22.6, 33.6) in 1996-99, as compared to 7.5/100 py (95% CI: 5.1, 10.6) in 2000-2005, and 4.9/100 py (95% CI: 3.1, 7.4) in 2006-2012. Unstable housing, HIV infection, and injecting of cocaine, heroin and methamphetamine were independently associated with HCV seroconversion., Conclusions: HCV incidence has dramatically declined among PWID in this setting. However, improved public health strategies to prevent and treat HCV are urgently required to reduce HCV-associated morbidity and mortality.

HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979-1989) and 382 modern (2000-2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a "consensus-like" founder virus, the median "background" frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ∼ 2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were "pre-adapted" to the average host HLA profile was only ∼ 2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins.

Food insecurity may be a barrier to achieving optimal HIV treatment-related outcomes among illicit drug users. This study therefore, aimed to assess the impact of severe food insecurity, or hunger, on plasma HIV RNA suppression among illicit drug users receiving antiretroviral therapy (ART). A cross-sectional Multivariate logistic regression model was used to assess the potential relationship between hunger and plasma HIV RNA suppression. A sample of n = 406 adults was derived from a community-recruited open prospective cohort of HIV-positive illicit drug users, in Vancouver, British Columbia (BC), Canada. A total of 235 (63.7%) reported "being hungry and unable to afford enough food," and 241 (59.4%) had plasma HIV RNA < 50 copies/ml. In unadjusted analyses, self-reported hunger was associated with lower odds of plasma HIV RNA suppression (Odds Ratio = 0.59, 95% confidence interval [CI]: 0.39-0.90, p = 0.015). In multivariate analyses, this association was no longer significant after controlling for socio-demographic, behavioral, and clinical characteristics, including 95% adherence (Adjusted Odds Ratio [AOR] = 0.65, 95% CI: 0.37-1.10, p = 0.105). Multivariate models stratified by 95% adherence found that the direction and magnitude of this association was not significantly altered by the adherence level. Hunger was common among illicit drug users in this setting. Although, there was an association between hunger and lower likelihood of plasma HIV RNA suppression, this did not persist in adjusted analyses. Further research is warranted to understand the social-structural, policy, and physical factors shaping the HIV outcomes of illicit drug users.

We sought to examine whether methadone maintenance therapy (MMT) decreased rates of antiretroviral therapy (ART) discontinuation and was associated with plasma HIV RNA responses among a cohort of illicit drug users. Cumulative ART discontinuation rates were estimated using Kaplan-Meier methods and factors independently associated with ART discontinuation were identified using Cox proportional hazards regression. Engagement in MMT was negatively and independently associated with ART discontinuation [Adjusted Relative Hazard = 0.67 (95 % CI 0.54-0.83); p < 0.001]. Among participants receiving ART and MMT, 81.6 % of plasma HIV-1 RNA assessments were <500 copies/mL, while 65.81 % of HIV-1 RNA assessments among those prescribed ART without MMT were <500 copies/mL (p < 0.001). These results demonstrate that engagement in MMT conferred a protective benefit against ART discontinuation and was associated with a significant increase in plasma HIV RNA suppression among HIV-infected opioid-dependent drug users.

Objective: Given the link between employment and mortality in the general population, we sought to assess this relationship among HIV-positive people who use illicit drugs in Vancouver, Canada., Methods: Data were derived from a prospective cohort study of HIV seropositive people who use illicit drugs (n=666) during the period of May 1996-June 2010 linked to comprehensive clinical data in Vancouver, Canada, a setting where HIV care is delivered without charge. We estimated the relationship between employment and mortality using proportional hazards survival analysis, adjusting for relevant behavioural, clinical, social and socioeconomic factors., Results: In a multivariate survival model, a time-updated measure of full time, temporary or self-employment compared with no employment was significantly associated with a lower risk of death (adjusted HR=0.44, 95% CI 0.22 to 0.91). Results were robust to adjustment for relevant confounders, including age, injection and non-injection drug use, plasma viral load and baseline CD4 T-cell count., Conclusions: These findings suggest that employment may be an important dimension of mortality risk of HIV-seropositive illicit drug users. The potentially health-promoting impacts of labour market involvement warrant further exploration given the widespread barriers to employment and persistently elevated levels of preventable mortality among this highly marginalised population.

Background: Informed by recent studies demonstrating the central role of plasma HIV-1 RNA viral load (VL) on HIV transmission, interventions to employ HIV antiretroviral treatment as prevention (TasP) are underway. To optimize these efforts, evidence is needed to identify factors associated with both non-suppressed VL and HIV risk behaviours. Thus, we sought to assess the possible role played by exposure to correctional facilities on VL non-suppression and used syringe lending among HIV-seropositive people who use injection drugs (PWID)., Methods: We used data from the ACCESS study, a community-recruited prospective cohort. We used longitudinal multivariate mixed-effects analyses to estimate the relationship between incarceration and plasma HIV-1 RNA > 500 copies/mL among antiretroviral therapy (ART)-exposed active PWID and, during periods of non-suppression, the relationship between incarceration and used syringe lending., Results: Between May 1996 and March 2012, 657 ART-exposed PWID were recruited. Incarceration was independently associated with higher odds of VL non-suppression (Adjusted Odds Ratio [AOR] = 1.54, 95% Confidence Interval [95% CI]: 1.10, 2.16). In a separate multivariate model restricted to periods of VL non-suppression, incarceration was independently associated with lending used syringes (AOR = 1.81, 95% CI: 1.03, 3.18)., Conclusions: The current findings demonstrate that incarceration is associated with used syringe lending among active PWID with detectable plasma HIV-1 RNA. Our results provide a possible pathway for the commonly observed association between incarceration and increased risk of HIV transmission. Our results suggest that alternatives to incarceration of non-violent PWID and evidence-based combination HIV prevention interventions for PWID within correctional facilities are urgently needed.

We describe a reliable and semi-automated method for killer-cell immunoglobulin-like receptor (KIR) 3DL1/S1 genotyping using DNA recovered from frozen plasma. The primers and protocol were first validated using two independent genomic DNA reference panels. To confirm the approach using plasma-derived DNA, total nucleic acids were extracted from 69 paired frozen PBMC and plasma specimens representing all common KIR3DL1/S1 genotypes (3DS1/3DS1, 3DS1/3DL1 and 3DL1/3DL1, including rare allele 3DL1*054), and analyzed in a blinded fashion. The method involves independent nested PCR amplification of KIR3DL1/S1 Exon 4, and if required Exon 3, using universal sequence-specific primers, followed by bidirectional sequencing. The free basecalling software RECall is recommended for rapid, semi-automated chromatogram analysis. KIR3DL1/S1 type assignment is based on two key nucleotide polymorphisms in Exon 4 and, if required, up to two additional polymorphisms in exon 3. Assignment can be performed manually or using our web-based algorithm, KIR3D. Extractions from plasma yielded median [IQR] nucleic acid concentrations of 0.9 [below the limit of detection-2.45] ng/μl. PCR was successful for 100% of exon 4 (69/69) and exon 3 (29/29) plasma amplifications. Chromatogram quality was high and concordance between PBMC and plasma-derived types was 100%. The estimated lower limit of input DNA required for reliable typing is 0.01 ng/μl. This method provides reliable and accurate KIR3DL1/S1 typing when conventional sources of high-quality genomic DNA are unavailable or limiting., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: This study aimed to determine the baseline demographics, health status, and drug use profiles of current and former substance-using older adults in Vancouver's Downtown Eastside., Methods: Data were derived from two U.S. National Institutes of Health-funded cohort studies of current and former illegal drug users in Vancouver's Downtown Eastside. We used logistic regression of cross-sectional data obtained between June and November 2008 to calculate odds ratios and identify factors that were more commonly associated with cohort members being older adults (greater than or equal to age 50)., Results: 214 subjects (25%) were greater than or equal to age 50 upon study enrollment. Females (Adjusted Odds Ratio [AOR]: 0.50; 95% CI: 0.34-0.75) and individuals who reported Aboriginal ancestry (AOR: 0.49; 95% CI: 0.33-0.72) were less likely to be in the older cohort. Individuals with higher income (AOR: 2.07; 95% CI: 1.16-3.68 per $1,000), and those with a regular place to stay were more likely to be in older cohort (AOR: 3.39; 95% CI: 1.90-6.06). Older participants accessed family physicians more frequently (OR: 1.47; 95% CI: 1.01 - 2.16) and were more likely to be actively taking (OR: 3.34; 95% CI 1.71-6.55) or have taken (OR 3.21; 95% CI 1.58-6.53) HIV antiretroviral therapy. There were no differences between groups in regard to injection drug use status or daily alcohol intake., Conclusions: Older current and former illegal drug users in a major inner city Canadian centre have different demographic, health-care, and drug utilization profiles. Further studies in this population are warranted.

We investigated whether drug-related behaviors predicted antiretroviral therapy (ART) discontinuation among a cohort of injection drug users (IDU) in a Canadian setting. Cox regression analyses were used to investigate the impact of drug use patterns on rates of ART discontinuation among a sample of HIV-positive IDU in Vancouver, Canada between May 1996 and April 2008. In total, 408 HIV-positive IDU initiated ART during the study period, among whom 257 (63.0%) discontinued ART at least once. Rates of ART discontinuation were not significantly elevated among those who reported ongoing injection of heroin, cocaine, or other illicit drugs in comparison to those who reported not injecting drugs. However, public drug use was significantly predictive of ART discontinuation. Our findings may contribute to a reconsideration of the role of active drug use in determining retention in ART programs among IDU.

Individuals who are homeless or living in marginal conditions have an elevated burden of infection with HIV. Existing research suggests the HIV/AIDS pandemic in resource-rich settings is increasingly concentrated among members of vulnerable and marginalized populations, including homeless/marginally-housed individuals, who have yet to benefit fully from recent advances in highly-active antiretroviral therapy (HAART). We reviewed the scientific evidence investigating the relationships between inferior housing and the health status, HAART access and adherence and HIV treatment outcomes of people living with HIV/AIDS (PLWHA.) Studies indicate being homeless/marginally-housed is common among PLWHA and associated with poorer levels of HAART access and sub-optimal treatment outcomes. Among homeless/marginally-housed PLWHA, determinants of poorer HAART access/adherence or treatment outcomes include depression, illicit drug use, and medication insurance status. Future research should consider possible social- and structural-level determinants of HAART access and HV treatment outcomes that have been shown to increase vulnerability to HIV infection among homeless/marginally-housed individuals. As evidence indicates homeless/marginally-housed PLWHA with adequate levels of adherence can benefit from HAART at similar rates to housed PLWHA, and given the individual and community benefits of expanding HAART use, interventions to identify HIV-seropositive homeless/marginally-housed individuals, and engage them in HIV care including comprehensive support for HAART adherence are urgently needed.

Background: Drug injection in prison is associated with a high risk of transmission of blood-borne pathogens including hepatitis C (HCV). The aim of this study was to estimate the prevalence and identify independent correlates of recent in-prison injecting drug use (P-IDU) among a large sample of adult prisoners in Queensland, Australia., Methods: Confidential, structured interviews with 1,322 adult prisoners in Queensland, Australia. Prevalence estimates were corrected for sampling bias using inverse probability weighting. Independent correlates of recent P-IDU were identified using multivariable Poisson regression with backwards elimination., Results: We estimated that among all adult prisoners in Queensland, Australia, the prevalence of lifetime IDU was 55.1%, of lifetime P-IDU 23.0%, and of recent (during current sentence) P-IDU 13.2%. Significant, independent correlates of recent P-IDU included male gender (ARR=3.07, 95% CI 1.83-5.12), being unemployed prior to incarceration (ARR=1.34, 95% CI 1.01-1.76), use of three or more drug types prior to incarceration (ARR=1.80, 95% CI 1.40-2.31), a history of needle/syringe sharing (ARR=5.00, 95% CI 3.06-8.16), receiving a tattoo during the current prison sentence (ARR=2.19, 95% CI 1.67-2.86) and HCV exposure (ARR=1.47, 95% CI 1.08-2.02). Older age was protective (ARR=0.90 per 5 years older, 95% CI 0.83-0.99)., Conclusion: Drug injection in prison is common and, given the associations between in-prison drug injection and syringe sharing, unsafe tattooing and HCV exposure, poses a risk to both prisoner health and public health. There remains an urgent need to implement evidence-based infection control measures, including needle and syringe programs, within prison settings., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Adherence to antiretroviral therapy (ART) among injecting drug users (IDUs) is often suboptimal, yet little is known about changes in patterns of adherence since the advent of highly active antiretroviral therapy in 1996. We sought to assess levels of optimal adherence to ART among IDUs in a setting of free and universal HIV care., Methods: Data were collected through a prospective cohort study of HIV-positive IDUs in Vancouver, British Columbia. We calculated the proportion of individuals achieving at least 95% adherence in the year following initiation of ART from 1996 to 2009., Results: Among 682 individuals who initiated ART, the median age was 37 years (interquartile range 31-44 years) and 248 participants (36.4%) were female. The proportion achieving at least 95% adherence increased over time, from 19.3% in 1996 to 65.9% in 2009 (Cochrane-Armitage test for trend: P < 0.001). In a logistic regression model examining factors associated with 95% adherence, initiation year was statistically significant (odds ratio 1.08; 95% confidence interval 1.03-1.13; P < 0.001 per year after 1996) after adjustment for a range of drug use variables and other potential confounders., Conclusions: The proportion of IDUs achieving at least 95% adherence during the first year of ART has consistently increased over a 13-year period. Although improved tolerability and convenience of modern ART regimens probably explain these positive trends, by the end of the study period a substantial proportion of IDUs still had suboptimal adherence, demonstrating the need for additional adherence support strategies., (© 2012 British HIV Association.)

We describe a rapid, reliable and cost-effective method for intermediate-to-high-resolution sequence-based HLA class I typing using frozen plasma as a source of genomic DNA. The plasma samples investigated had a median age of 8.5 years. Total nucleic acids were isolated from matched frozen PBMC (~2.5 million) and plasma (500 μl) samples from a panel of 25 individuals using commercial silica-based kits. Extractions yielded median [IQR] nucleic acid concentrations of 85.7 [47.0-130.0]ng/μl and 2.2 [1.7-2.6]ng/μl from PBMC and plasma, respectively. Following extraction, ~1000 base pair regions spanning exons 2 and 3 of HLA-A, -B and -C were amplified independently via nested PCR using universal, locus-specific primers and sequenced directly. Chromatogram analysis was performed using commercial DNA sequence analysis software and allele interpretation was performed using a free web-based tool. HLA-A, -B and -C amplification rates were 100% and chromatograms were of uniformly high quality with clearly distinguishable mixed bases regardless of DNA source. Concordance between PBMC and plasma-derived HLA types was 100% at the allele and protein levels. At the nucleotide level, a single partially discordant base (resulting from a failure to call both peaks in a mixed base) was observed out of >46,975 bases sequenced (>99.9% concordance). This protocol has previously been used to perform HLA class I typing from a variety of genomic DNA sources including PBMC, whole blood, granulocyte pellets and serum, from specimens up to 30 years old. This method provides comparable specificity to conventional sequence-based approaches and could be applied in situations where cell samples are unavailable or DNA quantities are limiting., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Human immunodeficiency virus (HIV)-positive injection drug users (IDUs) are known to be at risk for multiple medical problems that may necessitate emergency department (ED) use; however, the relative contribution of HIV disease vs. injection-related complications has not been well described., Objectives: We examined factors associated with ED use among a prospective cohort of HIV-positive IDUs in a Canadian setting., Methods: We enrolled HIV-positive IDUs into a community-recruited prospective cohort study. We modeled factors associated with the time to first ED visit using Cox regression to determine factors independently associated with ED use. In sub-analyses, we examined ED diagnoses and subsequent hospital admission rates., Results: Between December 5, 2005 and April 30, 2008, 428 HIV-positive IDUs were enrolled, among whom the cumulative incidence of ED use was 63.7% (95% confidence interval [CI] 59.1-68.3%) at 12 months after enrollment. Factors independently associated with time to first ED visit included: unstable housing (hazard ratio [HR] 1.5; 95% CI 1.1-2.0) and reporting being unable to obtain needed health care services (HR 2.2; 95% CI 1.2-4.1), whereas CD4 count and viral load were non-significant. Skin and soft tissue infections accounted for the greatest proportion of ED visits (17%). Of the 2461 visits to the ED, 419 (17%) were admitted to the hospital., Conclusions: High rates of ED use were observed among HIV-positive IDUs, a behavior that was predicted by unstable housing and limited access to primary care. Factors other than HIV infection seem to be driving ED use among this population in the post-highly active antiretroviral therapy era., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose of Review: Recent research has confirmed the efficacy of employing highly active antiretroviral therapy (HAART) to prevent the transmission of HIV. However, barriers to the use of HAART among people who use injection drugs (PWIDs) remain an international concern. We review recent findings regarding factors determining effective HIV treatment among PWIDs and describe their possible impact on efforts to curb HIV incidence using HAART., Recent Findings: Internationally, HIV-seropositive PWIDs continue to experience suboptimal HIV treatment outcomes compared with other risk groups. Recent findings have better elucidated the role of ongoing illicit drug use in limiting access and adherence to HAART. However, recent research has also increasingly demonstrated the important role that social, environmental and structural factors, resulting from the criminalization of PWIDs, have in placing barriers to optimal HAART use among this population., Summary: Treatment as prevention strategies for PWIDs will only be maximally effective if structural barriers to effective addiction and HIV treatment, which stem from the ongoing criminalization of this population, are addressed.

Background: Previous studies suggest that active drug use may compromise HIV treatment among HIV-positive injection drug users (IDU). However, little is known about the differential impacts of cocaine injection, heroin injection, and combined cocaine and heroin injection on plasma HIV-1 RNA suppression., Methods: Data were derived from a longstanding open prospective cohort of HIV-positive IDU in Vancouver, Canada. Kaplan-Meier methods and Cox proportional hazards regression were used to examine the impacts of different drug use patterns on rates of plasma HIV-1 RNA suppression., Results: Between May 1996 and April 2008, 267 antiretroviral (ART) naïve participants were seen for a median follow-up duration of 50.6 months after initiating ART. The incidence density of HIV-1 RNA suppression was 65.2 (95%CI: 57.0-74.2) per 100 person-years. In Kaplan-Meier analyses, compared to those who abstained from injecting, individuals injecting heroin, cocaine, or combined heroin/cocaine at baseline were significantly less likely to achieve viral suppression (all p<0.01). However, none of the drug use categories remained associated with a reduced rate of viral suppression when considered as time-updated variables (all p>0.05)., Conclusions: Active injecting at the time of ART initiation was associated with lower plasma HIV-1 RNA suppression rates; however, there was no difference in suppression rates when drug use patterns were examined over time. These findings imply that adherence interventions for active injectors should optimally be applied at the time of ART initiation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Release from prison is associated with a markedly increased risk of both fatal and non-fatal drug overdose, yet the risk factors for overdose in recently released prisoners are poorly understood. The aim of this study was to identify risk and protective factors for non-fatal overdose (NFOD) among a cohort of illicit drug users in Vancouver, Canada, according to recent incarceration., Methods: Prospective cohort of 2515 community-recruited illicit drug users in Vancouver, Canada, followed from 1996 to 2010. We examined factors associated with NFOD in the past six months separately among those who did and did not also report incarceration in the last six months., Results: One third of participants (n=829, 33.0%) reported at least one recent NFOD. Among those recently incarcerated, risk factors independently and positively associated with NFOD included daily use of heroin, benzodiazepines, cocaine or methamphetamine, binge drug use, public injecting and previous NFOD. Older age, methadone maintenance treatment and HIV seropositivity were protective against NFOD. A similar set of risk factors was identified among those who had not been incarcerated recently., Conclusions: Among this cohort, and irrespective of recent incarceration, NFOD was associated with a range of modifiable risk factors including more frequent and riskier patterns of drug use. Not all ex-prisoners are at equal risk of overdose and there remains an urgent need to develop and implement evidence-based preventive interventions, targeting those with modifiable risk factors in this high risk group., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Previous studies of adherence to antiretroviral therapy (ART) for HIV among young injection drug users (IDU) have been limited because financial barriers to care disproportionately affect youth, thus confounding results. This study examines adherence among IDU in a unique setting where all medical care is provided free-of-charge. From May 1996 to April 2008, we followed a prospective cohort of 545 HIV-positive IDU of 18 years of age or older in Vancouver, Canada. Using generalized estimating equations (GEE), we studied the association between age and adherence (obtaining ART≥95% of the prescribed time), controlling for potential confounders. Using Cox proportional hazards regression, we also studied the effect of age on time to viral load suppression (<500 copies per milliliter), and examined adherence as a mediating variable. Five hundred forty-five participants were followed for a median of 23.8 months (interquartile range [IQR]=8.5-91.6 months). Odds of adherence were significantly lower among younger IDU (adjusted odds ratio [AOR]=0.76 per 10 years younger; 95% confidence interval [CI], 0.65-0.89). Younger IDU were also less likely to achieve viral load suppression (adjusted hazard ratio [AHR]=0.75 per 10 years younger; 95% CI, 0.64-0.88). Adding adherence to the model eliminated this association with age, supporting the role of adherence as a mediating variable. Despite absence of financial barriers, younger IDU remain less likely to adhere to ART, resulting in inferior viral load suppression. Interventions should carefully address the unique needs of young HIV-positive IDU.

Introduction: Evidence is needed to improve HIV treatment outcomes for individuals who use injection drugs (IDU). Although studies have suggested higher rates of plasma viral load (PVL) rebound among IDU on antiretroviral therapy (ART), risk factors for rebound have not been thoroughly investigated., Methods: We used data from a long-running community-recruited prospective cohort of IDU in Vancouver, Canada, linked to comprehensive ART and clinical monitoring records. Using proportional hazards methods, we modeled the time to confirmed PVL rebound above 1000 copies per milliliter among IDU on ART with sustained viral suppression, defined as 2 consecutive undetectable PVL measures., Results: Between 1996 and 2009, 277 individuals had sustained viral suppression. Over a median follow-up of 32 months, 125 participants (45.1%) experienced at least 1 episode of virologic failure for an incidence of 12.6 [95% confidence interval (CI): 10.5 to 15.0] per 100 person-years. In a multivariate model, PVL rebound was independently associated with sex-trade involvement [adjusted hazard ratio (AHR) = 1.40, 95% CI: 1.08 to 1.82) and recent incarceration (AHR = 1.83, 95% CI: 1.33 to 2.52). Methadone maintenance therapy (AHR = 0.79, 95% CI: 0.66 to 0.94) was protective. No measure of illicit drug use was predictive., Conclusions: In this setting of free ART, several social and environmental factors predicted higher risks of viral rebound among IDU, including sex-trade involvement and incarceration. These findings should help inform efforts to identify individuals at risk of viral rebound and targeted interventions to treat and retain individuals in effective ART.

Purpose of Review: The use of highly active antiretroviral therapy (HAART) as a strategy to prevent the transmission of HIV infection is of substantial international interest. Injection drug users (IDUs) are an important population with respect to HIV treatment as prevention because they are often less likely to access HAART in comparison with other risk groups., Recent Findings: A recent multicentre randomized clinical trial demonstrated a 96% reduction in HIV transmission among heterosexual serodiscordant couples prescribed early HAART. Consistent with these results, independent observational studies from Baltimore and Vancouver have demonstrated that population level rates of HAART use among IDUs are associated with reduced rates of HIV incidence. In addition, impact assessments of HAART delivery to IDUs have generally demonstrated no negative effects of HAART use on rates of unsafe sex or syringe sharing., Summary: HAART prevents HIV transmission because it dramatically decreases HIV-1 RNA levels in biological fluids. This is relevant to vertical and sexual HIV transmission and also to blood-borne HIV transmission, as it is often the case among IDUs. Efforts to expand HAART to IDUs should be redoubled in an effort to realize both the individual and public health benefits of HAART.

Purpose: Illicit drug overdose is a leading cause of premature mortality. We sought to examine fatal overdose trends from 2001 to 2005 in urban and nonurban areas of British Columbia, Canada., Methods: We conducted a review of all provincial coroner files in which drug overdose was the cause of death between January 1, 2001, and December 31, 2005. We compared cocaine and non-cocaine-related overdoses and examined temporal changes in cocaine-related mortality rates in urban and nonurban areas. Multilevel mixed effects models were used to determine the independent risk factors for cocaine-related death. Spatial analyses were conducted to identify clusters of these cases., Results: During the study period, 904 illicit drug overdoses were recorded, including 369 (40.8%) in nonurban areas and 532 (58.9%) related to cocaine consumption. In a multilevel model, we observed a significant interaction (p = .010) between population density and year, indicating a considerable and differential increase in the likelihood of cocaine-related deaths in nonurban areas. Cocaine-related deaths were clustered in the southeast region of the province., Conclusions: Cocaine-related overdoses in nonurban areas should be a public health concern. Evidence-based interventions to reduce the risks associated with cocaine consumption and reach drug users in nonurban settings are needed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Despite the availability of antiretroviral therapy (ART), suboptimal treatment outcomes have been observed among HIV-seropositive illicit drug users. As there is an urgent need to improve responses to antiretroviral therapy among this population, we undertook this study to evaluate the role of physician experience on rates of plasma HIV-1 RNA suppression following initiation of ART., Methods: Using data from a community-recruited cohort of HIV-positive illicit drug users, we used Cox proportional hazards regression to model the time to plasma viral HIV RNA < 500 copies/mL among antiretroviral-naïve subjects initiating ART. Physician experience was defined as a continuous variable measured per 100 HIV-infected patients previously enrolled in the province-wide HIV treatment registry by that physician at the time a patient was enrolled., Results: Between May 1996 and December 2008, 267 individuals initiated ART among whom 227 (85%) achieved a plasma HIV RNA < 500 copies/mL during the study period. In a multivariate analysis, greater physician experience was independently associated with higher rates of plasma HIV RNA suppression (adjusted hazard ratio [AHR] = 1.17, 95% confidence interval [CI]: 1.03-1.34) after adjustment for adherence to ART. Other factors associated with viral suppression included engagement in methadone maintenance therapy (AHR = 1.61, 95% CI: 1.23-2.09), ≥ 95% adherence to ART (AHR = 2.42, 95% CI: 1.80-3.26), baseline CD4 count (AHR = 0.89, 95% CI: 0.83-0.96) and baseline plasma HIV-1 RNA (AHR = 0.65, 95% CI: 0.53-0.81)., Conclusions: In this setting of universal HIV/AIDS care, illicit drug users with more experienced physicians exhibited faster rates of plasma viral load suppression. These findings argue for specialized services to help optimize HIV treatment outcomes among this population.