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1.  The impact of unstable housing on emergency department use in a cohort of HIV-positive people in a Canadian setting 
AIDS care  2013;26(1):53-64.
The social-structural challenges experienced by people living with HIV (PHA) have been shown to contribute to increased use of the Emergency Department (ED). This study identified factors associated with frequent and non-urgent ED use within a cohort of people accessing antiretroviral therapy (ART) in a Canadian setting. Interviewer-administered surveys collected socio-demographic information; clinical variables were obtained through linkages with the provincial drug treatment registry; and ED admission data were abstracted from the Department of Emergency Medicine database. Multivariate logistic regression was used to compute odds of frequent and non-urgent ED use. Unstable housing was independently associated with ED use (adjusted odds ratio [AOR]=1.94, 95% confidence interval [CI] 1.24–3.04]), having three or more ED visits within 6 months of interview date [AOR: 2.03 (95% CI: 1.07–3.83)] and being triaged as non-urgent (AOR=2.71, 95% CI: 1.19–6.17). Frequent and non-urgent use of the ED in this setting is associated with conditions requiring interventions at the social-structural level. Supportive housing may contribute to decreased healthcare costs and improved health outcomes amongst marginalized PHA.
doi:10.1080/09540121.2013.793281
PMCID: PMC4279918  PMID: 23656484
HIV; Emergency Department; Antiretroviral Therapy; marginalized Populations; housing
2.  HIV treatment as prevention: the key to an AIDS-free generation 
Journal of food and drug analysis  2013;21(4):S95-S101.
The presence of elevated HIV viral load within blood and genital secretions is a critical driver of transmission events. Long-term suppression of viral load to undetectable levels through the use of antiretroviral therapy is now standard practice for clinical management of HIV. Antiretroviral therapy therefore can play a key role as a means to curb HIV transmission. Results of a randomized clinical trial, in conjunction with several observational studies, have now confirmed that antiretroviral therapy markedly decreases HIV transmission risk. Mathematical models and population-based ecologic studies suggest that further expansion of antiretroviral coverage within current guidelines can play a major role in controlling the spread of HIV. Expansion of so-called “Treatment as Prevention” initiatives relies upon maximal uptake of the HIV continuum-of-care cascade to allow for successful identification of those not yet known to be HIV-infected, engagement of patients in appropriate care, and subsequently achieving sustained virologic suppression in patients with the use of antiretroviral therapy. Since 2010, the Joint United Nations AIDS (UNAIDS) program has called for the inclusion of antiretroviral treatment as a key pillar in the global strategy to control the spread of HIV infection. This has now been invigorated by the release of the World Health Organization’s 2013 Consolidated Antiretroviral Therapy Guidelines, recommending treatment to be offered to all HIV-infected individuals with CD4 cell counts below 500/mm3, and, regardless of CD4 cell count, to serodiscordant couples, TB and HBV co-infected individuals, pregnant women, and children below the age of 5 years.
doi:10.1016/j.jfda.2013.09.043
PMCID: PMC4158850  PMID: 25214752
HIV care cascade; linkage to care; Seek and Treat; Treatment as Prevention
3.  Expanded HAART Coverage is Associated with Decreased Population-level HIV-1-RNA and Annual New HIV Diagnoses in British Columbia, Canada 
Lancet  2010;376(9740):532-539.
Background
Cohort studies and mathematical models have suggested that expanded coverage with highly active antiretroviral therapy (HAART) could decrease HIV transmission. This study focuses on the HIV epidemic, stratified by injection drug use, in the province of British Columbia, Canada, and seeks to estimate the association between plasma HIV-1-viral load, HAART coverage and number of new cases of HIV at the population-level.
Methods
HAART use, plasma HIV-1-viral level determinations, and rates of reportable sexually transmitted infections, including HIV, are all recorded in province-wide registries allowing for temporal comparisons of these parameters. Trends of new HIV positive tests and number of individuals on HAART were modeled using generalized additive models. Poisson log-linear regression models were used to estimate the association between the outcome new HIV positive tests (per 100 population) and the covariates viral load (log10 transformed), year, and number of individuals on HAART.
Conclusions
Our results demonstrate a strong association at the population-level between increasing levels of HAART coverage, decreased viral load and decreased new HIV diagnoses/year, against a background of increased HIV testing and increased rates of other STIs in the province. Our results support the proposed secondary benefit of HAART, used within current medical guidelines, on HIV transmission at a population level.
doi:10.1016/S0140-6736(10)60936-1
PMCID: PMC2996043  PMID: 20638713
4.  The Effect of History of Injection Drug Use and Alcoholism on HIV Disease Progression 
AIDS care  2013;26(1):10.1080/09540121.2013.804900.
The effectiveness of highly active antiretroviral therapy (HAART) in preventing disease progression can be negatively influenced by the high prevalence of substance use among patients. Here, we quantify the effect of history of injection drug use and alcoholism on virologic and immunologic response to HAART. Clinical and survey data, collected at the start of HAART and at the interview date, were based on the study Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) in British Columbia, Canada. Substance use was a three-level categorical variable, combining information on history of alcohol dependence and of injection drug use, defined as: no history of alcohol and injection drug use, history of alcohol or injection drug use and history of both alcohol and injection drug use. Virologic response (pVL) was defined by ≥2 log10 copy/mL drop in viral load. Immunologic response was defined as an increase in CD4 cell count percent of ≥100%. We used cumulative logit modeling for ordinal responses to address our objective. Of the 537 HIV-infected patients, 112 (21%) were characterized as having history of both alcohol and injection drug use, 173 (32%) were non adherent (<95%), 196 (36%) had CD4+/pVL+ (Best) response, 180 (34%) a CD4+/pVL− or a CD4−/pVL+ (Incomplete) response, and 161 (30%) a CD4−/pVL− (Worst) response. For individuals with history of both alcohol and injection drug use, the estimated probability of of Best, Incomplete and Worse responses, respectively. Screening and detection of substance dependence will identify individuals at high-risk for non-adherence and ideally prevent their HIV disease from progressing to advanced stages where HIV disease can become difficult to manage.
doi:10.1080/09540121.2013.804900
PMCID: PMC3795995  PMID: 23767757
Alcohol; Injection drug use; Adherence; HAART; HIV; Disease progression
5.  Factors Associated With Mortality of HIV-Positive Clients Receiving Methadone Maintenance Treatment in China 
The Journal of Infectious Diseases  2013;208(3):442-453.
Background. Little is known about mortality of opiate users attending methadone maintenance treatment (MMT) clinics. We sought to investigate mortality and its predictors among human immunodeficiency virus (HIV)–positive MMT clients.
Methods. Records of 306 786 clients enrolled in China's MMT program from 24 March 2004 to 30 April 2011 were abstracted. Mortality rates were calculated for all HIV-positive antiretroviral treatment (ART)–naive and ART-experienced clients. Risk factors were examined using stratified proportional hazard ratios (HRs).
Results. The observed mortality rate for all clients was 11.8/1000 person-years (PY, 95% confidence interval [CI], 11.5–12.1) and 57.2/1000 PY (CI, 54.9–59.4) for HIV-positive clients (n = 18 193). An increase in average methadone doses to >75 mg/day was associated with a 24% reduction in mortality (HR = 0.76, CI, .70–.82), a 48% reduction for ART-naive HIV-positive clients (HR = 0.52, CI, .42–.65), and a 47% reduction for ART-experienced HIV-positive clients (HR = 0.53, CI, .46–.62). Among ART-experienced clients, initiation of ART when the CD4+ T-cell count was >300 cells/mm3 (HR = 0.64, CI, .43–.94) was also associated with decreased risk of death.
Conclusions. We found high mortality rates among HIV-positive MMT clients, yet decreased risk of death, with earlier ART initiation and higher methadone doses. A higher daily methadone dose was associated with reduced mortality in both HIV-infected and HIV-uninfected clients, independent of ART.
doi:10.1093/infdis/jit163
PMCID: PMC3698997  PMID: 23592864
mortality; HIV; drug users; methadone maintenance treatment; China
6.  Expansion of HAART Coverage Is Associated with Sustained Decreases in HIV/AIDS Morbidity, Mortality and HIV Transmission: The “HIV Treatment as Prevention” Experience in a Canadian Setting 
PLoS ONE  2014;9(2):e87872.
Background
There has been renewed call for the global expansion of highly active antiretroviral therapy (HAART) under the framework of HIV treatment as prevention (TasP). However, population-level sustainability of this strategy has not been characterized.
Methods
We used population-level longitudinal data from province-wide registries including plasma viral load, CD4 count, drug resistance, HAART use, HIV diagnoses, AIDS incidence, and HIV-related mortality. We fitted two Poisson regression models over the study period, to relate estimated HIV incidence and the number of individuals on HAART and the percentage of virologically suppressed individuals.
Results
HAART coverage, median pre-HAART CD4 count, and HAART adherence increased over time and were associated with increasing virological suppression and decreasing drug resistance. AIDS incidence decreased from 6.9 to 1.4 per 100,000 population (80% decrease, p = 0.0330) and HIV-related mortality decreased from 6.5 to 1.3 per 100,000 population (80% decrease, p = 0.0115). New HIV diagnoses declined from 702 to 238 cases (66% decrease; p = 0.0004) with a consequent estimated decline in HIV incident cases from 632 to 368 cases per year (42% decrease; p = 0.0003). Finally, our models suggested that for each increase of 100 individuals on HAART, the estimated HIV incidence decreased 1.2% and for every 1% increase in the number of individuals suppressed on HAART, the estimated HIV incidence also decreased by 1%.
Conclusions
Our results show that HAART expansion between 1996 and 2012 in BC was associated with a sustained and profound population-level decrease in morbidity, mortality and HIV transmission. Our findings support the long-term effectiveness and sustainability of HIV treatment as prevention within an adequately resourced environment with no financial barriers to diagnosis, medical care or antiretroviral drugs. The 2013 Consolidated World Health Organization Antiretroviral Therapy Guidelines offer a unique opportunity to further evaluate TasP in other settings, particularly within generalized epidemics, and resource-limited setting, as advocated by UNAIDS.
doi:10.1371/journal.pone.0087872
PMCID: PMC3922718  PMID: 24533061
7.  Identifying self-perceived HIV-related stigma in a population accessing antiretroviral therapy 
AIDS care  2012;25(1):10.1080/09540121.2012.687809.
This study identifies factors associated with self-perceived HIV-related stigma (stigma) among a cohort of individuals accessing antiretroviral therapy (ART) in British Columbia, Canada. Data were drawn from the Longitudinal Investigations into Supportive and Ancillary Health Services study, which collects social, clinical, and quality of life (QoL) information through an interviewer-administered survey. Clinical variables (i.e. CD4 count) were obtained through linkages with the British Columbia HIV/AIDS Drug Treatment Program. Multivariable linear regression was performed to determine the independent predictors of stigma. Our results indicate that among participants with high school education or greater the outcome stigma, was associated with a 3.05 stigma unit decrease (95% CI: −5.16, −0.93). Having higher relative standard of living and perceiving greater neighborhood cohesion were also associated with a decrease in stigma (−5.30 95% CI: −8.16, −2.44; −0.80 95% CI: −1.39, −0.21, respectively). Lower levels of stigma were found to be associated with better QoL measures, including perceiving better overall function (−0.90 95% CI: −1.47, −0.34), having fewer health worries (−2.11 95% CI: −2.65, −1.57), having fewer financial worries (−0.67 95% CI: −1.12, −0.23), and having less HIV disclosure concerns (−4.12 95% CI: −4.63, −3.62). The results of this study show that participants with higher education level, better QoL measures, and higher self-reported standards of living are less likely to perceive HIV-related stigma.
doi:10.1080/09540121.2012.687809
PMCID: PMC3879041  PMID: 22672228
stigma; ART; quality of life; HIV
8.  Does Initiation of HIV Antiretroviral Therapy Influence Patterns of Syringe Lending Among Injection Drug Users? 
Addictive behaviors  2011;36(5):560-563.
The delivery of antiretroviral therapy (ART) to injection drug users (IDU) may be influenced by provider concerns regarding the potential for increased HIV-related risk behavior following the initiation of HIV treatment. We evaluated whether ART initiation was associated with changes in syringe lending patterns among a long-term prospective cohort of HIV-positive IDU in Vancouver, Canada. Among 380 ART-naïve individuals eligible for this analysis, the median age was 34.2 (interquartile range [IQR] 27.7 – 40.8), 171 (45.0%) were female, and the median follow-up duration was 60 months (IQR = 18 – 113). Between May 1996 and April 2008, 260 (68.4%) participants initiated ART. In a generalized linear mixed-effects model which compared each individual’s likelihood of sharing syringes prior to and following the initiation of ART, syringe lending was not significantly associated with ART initiation in unadjusted (odds ratio = 0.72, 95% CI: 0.38 – 1.36) or adjusted (odds ratio = 0.78, 95% CI: 0.42 – 1.45) analyses. Concerns regarding increased injection risk behaviors following the initiation of ART were not observed in this setting.
doi:10.1016/j.addbeh.2011.01.022
PMCID: PMC3053580  PMID: 21320757
injection drug use; antiretroviral therapy; syringe lending; HIV
9.  Risk of Viral Failure Declines with Duration of Suppression on HAART, Irrespective of Adherence Level 
Objective
To model the effect of adherence and duration of viral suppression on the risk of viral rebound.
Methods
Viral rebound was defined as the first of at least 2 consecutive viral loads >400 copies/mL following initial viral suppression. The main exposures were adherence, presence of ARV class resistance before rebound or censoring date, and the percentage of follow-up time with viral suppression.
Results
A total of 274 (N=1305; 21%) individuals experienced viral rebound. Median time of suppression before rebound was 2 years. Viral rebound was less likely to occur among those with longer duration of continuous viral suppression (odds ratio 0.37; 95% confidence interval [CI] 0.32-0.42). Among individuals with moderate levels of adherence (80%-<95%), the probability of virologic failure was 0.85 after being suppressed for 12 months and it was 0.08 after 72 months being suppressed (p-value <0.01). Individuals with drug resistance were at a higher risk of viral rebound.
Conclusions
The risk of viral rebound decreased with longer duration of viral suppression within each of adherence strata studied. While perfect adherence remains an important goal of therapy to prevent disease progression, individuals with long-term viral suppression may be able to miss more doses without experiencing viral rebound.
doi:10.1097/QAI.0b013e3181f2ac87
PMCID: PMC2974791  PMID: 20838225
Adherence; HAART; virologic failure; viral rebound; resistance; long-term suppression
10.  No Evidence of Increased Sexual Risk Behaviour after Initiating Antiretroviral Therapy among People who Inject Drugs 
AIDS (London, England)  2010;24(14):2271-2278.
Objective
Although antiretroviral therapy (ART) dramatically reduces viral load and improves survival among HIV-infected injection drug users (IDU), several short-term studies have raised concerns that ART initiation may result in increases in sexual risk behaviour among IDU.
Design
We used data from a long-running cohort of HIV-positive IDU to examine whether ART initiation was associated with increases in several measures of sexual risk behaviour. The date of ART initiation was determined through a validated linkage to a centralized ART dispensation pharmacy.
Methods
We used generalized linear mixed-effects modeling to examine whether sexual activity, unprotected intercourse, and multiple sexual partnerships were more likely in the 12 month period following ART initiation.
Results
Among 457 individuals who were ART naïve at baseline, the median age was 34 (interquartile range [IQR]: 28–41) and 202 (44.2%) were female. Between May 1996 and April 2008, 260 (56.7%) participants initiated ART. In multivariate analyses, ART initiation was not associated with sexual activity (adjusted Odds Ratio [AOR] = 0.87, 95%CI: 0.60–1.25), unprotected intercourse (AOR = 0.82, 95%CI: 0.51–1.31), or multiple sexual partnerships (AOR = 0.93, 95%CI: 0.61–1.40).
Conclusions
In this study of HIV-positive IDU, we failed to detect an increase in sexual risk behaviour during the period following ART initiation. In light of this evidence, and given the known positive effect of ART on survival and its potential role in reducing HIV transmission, concerns regarding potential increases in sexual risk-taking should not undermine the delivery of ART to IDU.
doi:10.1097/QAD.0b013e32833dd101
PMCID: PMC2929971  PMID: 20683314
injection drug use; antiretroviral therapy; sexual risk; HIV; AIDS
11.  HIGH RATES OF HOMELESSNESS AMONG A COHORT OF STREET-INVOLVED YOUTH 
Health & place  2008;15(1):10-17.
Using multivariate logistic regression, we examined the prevalence and correlates of homelessness among youth enrolled in a community-recruited prospective cohort known as the At-Risk Youth Study (ARYS), between September 2005 and October 2006. Of 478 individuals included in this analysis, 132 (27.6%) were female and 120 (25.1%) self-identified as Aboriginal. The median age was 22 (IQR: 20–24). In total, 284 (56.9%) participants reported baseline homelessness, with most living either at no fixed address, on the street, or in a hostel or shelter. Factors associated with homelessness included public injecting, frequent crack use, experienced violence, having less than a high-school education, and not having been in any addiction treatment. Homeless individuals were at-risk for various adverse health outcomes. These findings indicate the need for additional interventions, including residential addiction treatment, to address homelessness and drug use among youth.
doi:10.1016/j.healthplace.2008.01.008
PMCID: PMC2606292  PMID: 18358759
Homelessness; youth; drug use; risk behavior
13.  HIV VprR77Q mutation does not influence clinical response of individuals initiating Highly Active Antiretroviral Therapy 
VprR77Q has been associated with long-term nonprogressive (LTNP) HIV infection. We wished to investigate the prevalence, clinical correlates, and effect on treatment response of VprR77Q in a cohort of antiretroviral-naïve individuals initiating Highly Active Antiretroviral Therapy (HAART). Baseline plasma samples from 728 subjects were genotyped using RT-PCR and direct DNA sequencing. Cox proportional hazards regression was used to model the effects of VprR77Q on virologic and immunologic responses, and survival following initiation of HAART, over a median 4.5 years follow-up. We found that 308 subjects (42.3%) harbored VprR77Q alone or in combination with another amino acid, while 420 (57.7%) harbored an amino acid other than Q. A cross-sectional analysis found no correlation between R77Q and baseline plasma viral load (pVL), CD4 count, diagnosis of AIDS, or sociodemographic characteristics including age, gender and history of injection drug use (p > 0.1). In multivariate analyses, no significant associations between VprR77Q and initial pVL and CD4 responses to HAART (p > 0.1) or survival following initiation of treatment were observed. The high prevalence and the lack of association with pre-therapy clinical parameters in this cohort argue against an association of R77Q with LTNP status. These results do not support an association between R77Q and HAART response.
doi:10.1089/aid.2006.22.615
PMCID: PMC2423217  PMID: 16831085
HIV; Vpr; R77Q; antiretroviral therapy response; HOMER cohort
14.  Special Access Denied: A Case Study of Health Canada’s Special Access Program 
Healthcare Policy  2006;2(2):27-34.
This paper examines the ethical probity of Health Canada’s Special Access Program (SAP). The SAP is designed for patients with life-threatening conditions who require “emergency” access to drugs that are not authorized for use in Canada when conventional therapies have failed. We argue that the SAP inappropriately uses the tenets of evidence-based decision-making in situations where evidence-based decision-making is unfeasible. The SAP should abandon its pretence of evidence-based decision-making and adopt a transparent process in which the values guiding decisions are explicit and corrigible. We recommend the ethical principles of autonomy, non-maleficence, beneficence and justice.
PMCID: PMC2585435  PMID: 19305701
16.  Effect of serostatus for hepatitis C virus on mortality among antiretrovirally naive HIV-positive patients 
Background
We examined the effect of hepatitis C virus (HCV) seropositivity on risk of death among people receiving their first antiretroviral treatment (ART) for HIV infection.
Methods
In British Columbia, the HIV/ AIDS Drug Treatment Program is the only source of free ART. Patients who initiated a triple-drug ART regimen between July 31, 1996, and July 31, 2000, were included if they were ART-naive and had baseline HCV serological data. Outcomes of interest for survival analysis were deaths from natural and HIV-related causes, with a data cutoff of June 30, 2003.
Results
Of 1186 eligible subjects, 606 (51%) were HCV positive and 580, negative. Fewer HCV-positive people were male (78% v. 93%, p < 0.001) and had an AIDS diagnosis at baseline (11% v. 15%, p = 0.028). Their CD4 fraction was significantly higher at baseline (19% v. 16% of T lymphocytes, p < 0.001) but their absolute CD4 counts, log HIV viral load and the type of ART initiated were similar to those of HCV negative people. Of 163 deaths (from natural causes only) during the study period, 118 (19%) were in HCV positive and 45 (8%) in HCV negative patients (p < 0.001); of the 114 deaths attributed to HIV infection, these proportions were 79 (13%) versus 35 (6%; p < 0.001). After adjustment for potential confounders, HCV seropositivity remained predictive of death (adjusted hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.50– 3.21, p < 0.001), especially HIV-related death (adjusted HR 1.75, 95% CI 1.13– 2.72, p = 0.012).
Interpretation
In this population-based HIV treatment program, we found HCV seropositivity to be an independent predictor of mortality, especially death related to HIV infection.
doi:10.1503/cmaj.045202
PMCID: PMC1174855  PMID: 16027432
17.  Changes in public order after the opening of a medically supervised safer injecting facility for illicit injection drug users 
Background
North America's first medically supervised safer injecting facility for illicit injection drug users was opened in Vancouver on Sept. 22, 2003. Although similar facilities exist in a number of European cities and in Sydney, Australia, no standardized evaluations of their impact have been presented in the scientific literature.
Methods
Using a standardized prospective data collection protocol, we measured injection-related public order problems during the 6 weeks before and the 12 weeks after the opening of the safer injecting facility in Vancouver. We measured changes in the number of drug users injecting in public, publicly discarded syringes and injection-related litter. We used Poisson log-linear regression models to evaluate changes in these public order indicators while considering potential confounding variables such as police presence and rainfall.
Results
In stratified linear regression models, the 12-week period after the facility's opening was independently associated with reductions in the number of drug users injecting in public (p < 0.001), publicly discarded syringes (p < 0.001) and injection-related litter (p < 0.001). The predicted mean daily number of drug users injecting in public was 4.3 (95% confidence interval [CI] 3.5–5.4) during the period before the facility's opening and 2.4 (95% CI 1.9–3.0) after the opening; the corresponding predicted mean daily numbers of publicly discarded syringes were 11.5 (95% CI 10.0–13.2) and 5.4 (95% CI 4.7–6.2). Externally compiled statistics from the city of Vancouver on the number of syringes discarded in outdoor safe disposal boxes were consistent with our findings.
Interpretation
The opening of the safer injecting facility was independently associated with improvements in several measures of public order, including reduced public injection drug use and public syringe disposal.
doi:10.1503/cmaj.1040774
PMCID: PMC517857  PMID: 15451834
18.  Displacement of Canada's largest public illicit drug market in response to a police crackdown 
Background
Law enforcement is often used in an effort to reduce the social, community and health-related harms of illicit drug use by injection drug users (IDUs). There are, however, few data on the benefits of such enforcement or on the potential harms. A large-scale police “crackdown” to control illicit drug use in Vancouver's Downtown Eastside provided us with an opportunity to evaluate the effect.
Methods
As part of our ongoing prospective cohort study of IDUs in Vancouver, we examined data collected from 244 IDUs in the 3 months before the police crackdown and from 142 IDUs in the 3 months after the start of the crackdown, on Apr. 7, 2003. All study subjects were active drug users. We also examined external data on needle exchanges and syringe disposal.
Results
The 2 groups of IDUs were statistically similar: they were mainly young (mean age 39 years) and male (63%), and they had injected illicit drugs for 13 years on average. Ethnic background and the proportion homeless were also similar. There were no statistically significant reported differences (all p > 0.1) in the street price of heroin, cocaine or “crack” in the 2 periods. In the 3-month periods before and after the crackdown, respectively, the rates of daily heroin injection were 27.9% and 26.8%, daily cocaine injection 28.7% and 27.5%, and daily crack use 59.4% and 60.6% (all p > 0.1). The proportions of study subjects receiving methadone treatment, 41.0% and 44.4% (p = 0.516), did not differ. However, the proportions reporting a change in where drugs were used, 22.5% and 33.8% (p < 0.05), and the proportions reporting a change in the neighbourhood of use because of police presence, 18.1% and 26.8% (p < 0.05), increased significantly. Needle-exchange data confirmed that the community levels of drug use were unchanged. Disposal statistics demonstrated that the monthly average number of used syringes found on the streets outside the traditional area of drug use increased from 784 in the 3 months before Apr. 1 to 1253 in the subsequent 3 months (p = 0.002) and the monthly average number of used syringes found in public boxes for the safe disposal of syringes decreased from 865 to 502 (p = 0.018).
Interpretation
The effort to control illicit drug use did not alter the price of drugs or the frequency of use, nor did it encourage enrolment in methadone treatment programs. Several measures indicated displacement of injection drug use from the area of the crackdown into adjacent areas of the city, which has implications for both recruitment of new initiates into injection drug use and HIV prevention efforts.
doi:10.1503/cmaj.1031928
PMCID: PMC400719  PMID: 15136548
19.  Adverse effects of antiretroviral therapy for HIV infection 
LONG-TERM REMISSION OF HIV-1 DISEASE CAN BE READILY ACHIEVED by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.
PMCID: PMC315530  PMID: 14734438
20.  Adherence and plasma HIV RNA responses to highly active antiretroviral therapy among HIV-1 infected injection drug users 
Background
The benefits of highly active antiretroviral therapy (HAART) for the treatment of HIV infection are well documented, but concerns regarding access and adherence to HAART are growing. We evaluated virological responses to HAART among HIV-1 infected patients who were injection drug users (IDUs) in a population-based setting where HIV/AIDS care is delivered free of charge.
Methods
We evaluated previously untreated HIV-1 infected men and women who initiated HAART between Aug. 1, 1996, and July 31, 2000, and who were followed until Mar. 31, 2002, in a province-wide HIV treatment program. We used Kaplan–Meier methods and Cox proportional hazards regression in our evaluation of time to suppression (i.e., less than 500 copies/mL) and rebound (i.e., 500 copies/mL or more) of plasma HIV-1 RNA, with patients stratified according to whether or not they had a history of injection drug use.
Results
Overall, 1422 patients initiated HAART during the study period, of whom 359 (25.2%) were IDUs. In Kaplan–Meier analyses, the cumulative suppression rate at 12 months after initiation of HAART was 70.8% for non-IDUs and 51.4% for IDUs (p < 0.001) (these values include people who achieved suppression before 12 months but who might not have been followed for the full 12-month period). Among patients who achieved suppression of plasma HIV-1 RNA, the cumulative rebound rate at 12 months after initial suppression was 23.8% for non-IDUs and 34.7% for IDUs (p < 0.001). However, after adjustment for adherence and other covariates, the rates of HIV-1 RNA suppression (adjusted relative hazard 0.9, 95% confidence interval [CI] 0.7–1.0) and HIV-1 RNA rebound (adjusted relative hazard 1.3, 95% CI 1.0–1.6) were similar between non-IDUs and IDUs. Differences between non-IDUs and IDUs were even less pronounced in subanalyses that considered only therapy-adherent patients (p > 0.1).
Interpretation
Non-IDUs and IDUs had similar rates of HIV-1 RNA suppression and rebound after the initiation of HAART, once lower levels of adherence were taken into account. Nevertheless, the lower virological response rates among IDUs suggest that, unless interventions are undertaken to improve adherence, these patients may experience elevated rates of disease progression and use of medical services in our setting.
PMCID: PMC202281  PMID: 14517122
21.  Impact of supply-side policies for control of illicit drugs in the face of the AIDS and overdose epidemics: investigation of a massive heroin seizure 
Background
More than 93% of the nearly $500 million spent annually on Canada's drug strategy goes toward efforts to reduce the illicit drug supply. However, little is known about the effectiveness of this strategy. On Sept. 2, 2000, Canadian police seized approximately 100 kg of heroin in one of the nation's largest-ever seizures of this drug. An ongoing prospective cohort study of injection drug users afforded an opportunity to evaluate the impact of this seizure.
Methods
The Vancouver Injection Drug User Study is a prospective cohort study of injection drug users that began in 1996. The present study relied primarily on data acquired from participants who were seen during the 30-day periods immediately before and after the seizure. We compared drug use and behavioural characteristics, heroin and cocaine prices, and participants' reports of whether law enforcement had affected their source of drugs or the types of drugs available on the street, as well as overdoses, in these 2 periods.
Results
The 138 participants seen before the seizure were similar to the 123 participants seen after the seizure with respect to age, sex, ethnic background, education, HIV serostatus, neighbourhood residence, instability of housing, employment status, use of methadone maintenance therapy and all other measured potential confounders (all p > 0.10). We found no difference in the extent to which participants in the 2 groups reported daily use of heroin, frequency of nonfatal overdoses, or whether law enforcement had affected their source of drugs or the types of drugs available on the street (all p > 0.10). Although we detected no difference in the price of cocaine, the median reported price of heroin went down after the seizure (p = 0.034), which suggests that other shipments compensated for the seizure. External evaluations of deaths from overdoses and heroin purity indicated that the seizure had no impact, nor was any impact seen when the periods of analysis were extended.
Interpretation
The massive heroin seizure appeared to have no measurable public health benefit. Closer scrutiny of enforcement efforts is warranted to ensure that resources are delivered to the most efficient and cost-effective public health programs.
PMCID: PMC140425  PMID: 12538544
22.  Unsafe injection practices in a cohort of injection drug users in Vancouver: Could safer injecting rooms help? 
Background
In several European countries safer injecting rooms have reduced the public disorder and health-related problems of injection drug use. We explored factors associated with needle-sharing practices that could potentially be alleviated by the availability of safer injecting rooms in Canada.
Methods
The Vancouver Injection Drug User Study is a prospective cohort study of injection drug users (IDUs) that began in 1996. The analyses reported here were restricted to the 776 participants who reported actively injecting drugs in the 6 months before the most recent follow-up visit, during the period January 1999 to October 2000. Needle sharing was defined as either borrowing or lending a used needle in the 6-month period before the interview.
Results
Overall, 214 (27.6%) of the participants reported sharing needles during the 6 months before follow-up; 106 (13.7%) injected drugs in public, and 581 (74.9%) reported injecting alone at least once. Variables independently associated with needle sharing in a multivariate analysis included difficulty getting sterile needles (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.8–4.1), requiring help to inject drugs (adjusted OR 2.0, 95% CI 1.4–2.8), needle reuse (adjusted OR 1.8, 95% CI 1.3–2.6), frequent cocaine injection (adjusted OR 1.6, 95% CI 1.1–2.3) and frequent heroin injection (adjusted OR 1.5, 95% CI 1.04–2.1). Conversely, HIV-positive participants were less likely to share needles (adjusted OR 0.5, 95% CI 0.4–0.8), although 20.2% of the HIV-positive IDUs still reported sharing needles.
Interpretation
Despite the availability of a large needle-exchange program and targeted law enforcement efforts in Vancouver, needle sharing remains an alarmingly common practice in our cohort. We identified a number of risk behaviours — difficulty getting sterile needles, needle sharing and reuse, injection of drugs in public and injecting alone (one of the main contributing causes of overdose) — that may be alleviated by the establishment of supervised safer injecting rooms.
PMCID: PMC81364  PMID: 11531048
23.  Crystal methamphetamine initiation among street-involved youth 
Background
Although many settings have recently documented a substantial increase in the use of methamphetamine-type stimulants, recent reviews have underscored the dearth of prospective studies that have examined risk factors associated with the initiation of crystal methamphetamine use.
Objectives
Our objectives were to examine rates and risk factors for the initiation of crystal methamphetamine use in a cohort of street-involved youth.
Methods
Street-involved youth in Vancouver, Canada, were enrolled in a prospective cohort known as the At-Risk Youth Study (ARYS). A total of 205 crystal methamphetamine-naïve participants were assessed semi-annually and Cox regression analyses were used to identify factors independently associated with the initiation of crystal methamphetamine use.
Results
Among 205 youth prospectively followed from 2005 to 2012, the incidence density of crystal methamphetamine initiation was 12.2 per 100 person years. In Cox regression analyses, initiation of crystal methamphetamine use was independently associated with previous crack cocaine use (adjusted relative hazard [ARH] = 2.24 [95% CI: 1.20–4.20]) and recent drug dealing (ARH = 1.98 [95% CI: 1.05–3.71]). Those initiating methamphetamine were also more likely to report a recent nonfatal overdose (ARH = 3.63 [95% CI: 1.65–7.98]) and to be male (ARH = 2.12 [95% CI: 1.06–4.25]).
Conclusions
We identified high rates of crystal methamphetamine initiation among this population. Males those involved in the drug trade, and those who used crack cocaine were more likely to initiate crystal methamphetamine use. Evidence-based strategies to prevent and treat crystal methamphetamine use are urgently needed.
doi:10.3109/00952990.2013.836531
PMCID: PMC3934747  PMID: 24191637
Crystal methamphetamine; social harm; youth
24.  EMPLOYMENT PREDICTS DECREASED MORTALITY AMONG HIV-SEROPOSITIVE ILLICIT DRUG USERS IN A SETTING OF UNIVERSAL HIV CARE 
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.
doi:10.1136/jech-2013-202918
PMCID: PMC4060796  PMID: 24153247
25.  High Levels of Heterogeneity in the HIV Cascade of Care across Different Population Subgroups in British Columbia, Canada 
PLoS ONE  2014;9(12):e115277.
Background
The HIV cascade of care (cascade) is a comprehensive tool which identifies attrition along the HIV care continuum. We executed analyses to explicate heterogeneity in the cascade across key strata, as well as identify predictors of attrition across stages of the cascade.
Methods
Using linked individual-level data for the population of HIV-positive individuals in BC, we considered the 2011 calendar year, including individuals diagnosed at least 6 months prior, and excluding individuals that died or were lost to follow-up before January 1st, 2011. We defined five stages in the cascade framework: HIV ‘diagnosed’, ‘linked’ to care, ‘retained’ in care, ‘on HAART’ and virologically ‘suppressed’. We stratified the cascade by sex, age, risk category, and regional health authority. Finally, multiple logistic regression models were built to predict attrition across each stage of the cascade, adjusting for stratification variables.
Results
We identified 7621 HIV diagnosed individuals during the study period; 80% were male and 5% were <30, 17% 30–39, 37% 40–49 and 40% were ≥50 years. Of these, 32% were MSM, 28% IDU, 8% MSM/IDU, 12% heterosexual, and 20% other. Overall, 85% of individuals ‘on HAART’ were ‘suppressed’; however, this proportion ranged from 60%–93% in our various stratifications. Most individuals, in all subgroups, were lost between the stages: ‘linked’ to ‘retained’ and ‘on HAART’ to ‘suppressed’. Subgroups with the highest attrition between these stages included females and individuals <30 years (regardless of transmission risk group). IDUs experienced the greatest attrition of all subgroups. Logistic regression results found extensive statistically significant heterogeneity in attrition across the cascade between subgroups and regional health authorities.
Conclusions
We found that extensive heterogeneity in attrition existed across subgroups and regional health authorities along the HIV cascade of care in B.C., Canada. Our results provide critical information to optimize engagement in care and health service delivery.
doi:10.1371/journal.pone.0115277
PMCID: PMC4277297  PMID: 25541682

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