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1.  Predictors of unstructured antiretroviral treatment interruption and resumption among HIV-positive individuals in Canada 
HIV medicine  2014;16(2):76-87.
Background
Sustained optimal use of combination antiretroviral treatment (cART) has been shown to decrease morbidity, mortality and HIV transmission. However, incomplete adherence and treatment interruption (TI) remain challenges to the full realization of the promise of cART. We estimated trends and predictors of treatment interruption and resumption among individuals in the Canadian Observational Cohort (CANOC) collaboration.
Methods
cART-naïve individuals ≥18 years of age who initiated cART between 2000–2011 were included. We defined TIs as ≥90 consecutive days off cART. We used descriptive analyses to study TI trends over time and Cox regression to identify factors predicting time to first TI and time to treatment resumption after a first TI.
Results
7,633 participants were eligible, of whom 1,860 (24.5%) experienced a TI. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Our analyses highlighted a higher risk of TI among women (adjusted hazard ratio (aHR): 1.59, 95%CI: 1.33–1.92), younger individuals (aHR: 1.27, 95%CI: 1.15–1.37 per decade increase), earlier treatment initiators (CD4 count ≥350 versus <200 mm3, aHR: 1.46, 95%CI: 1.17–1.81), Aboriginal participants (aHR: 1.67, 95%CI: 1.27–2.20), injecting drug users (aHR: 1.43, 95%CI: 1.09–1.89), and users of zidovudine versus tenofovir in the initial cART regimen (aHR: 2.47, 95%CI: 1.92–3.20). Conversely, factors predicting treatment resumption were male sex, older age, and a CD4 cell count <200 mm3 at cART initiation.
Conclusion
Despite significant improvements in cART since its advent, our results demonstrate that TIs remain relatively prevalent. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART.
doi:10.1111/hiv.12173
PMCID: PMC4300259  PMID: 25174373
Treatment interruption; HIV; antiretroviral therapy; retention; Canada
2.  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
3.  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
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.  Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting 
Objectives
To explore factors associated with early sex work initiation, and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs).
Design
Baseline data (2010–2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time-location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old.
Methods
SWs completed a questionnaire and HIV/STI testing. Using multivariate logistic regression, we identified associations with early sex work initiation (<18 years old) and constructed confounder models examining the independent effect of early initiation on HIV and prostitution arrests among adult SWs.
Results
Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian-born (Adjusted Odds Ratio (AOR): 6.8, 95% Confidence Interval (CI): 2.42–19.02), inject drugs (AOR: 1.6, 95%CI: 1.0–2.5), and to have worked for a manager (AOR: 2.22, 95%CI: 1.3–3.6) or been coerced into sex work (AOR: 2.3, 95%CI: 1.14–4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3–3.2) and prostitution arrests (AOR: 2.0, 95%CI: 1.3–3.2).
Conclusions
Adolescent sex work initiation is concentrated among marginalized, drug and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs.
doi:10.1097/QAI.0b013e3182a98ee6
PMCID: PMC4056677  PMID: 23982660
sex work; youth; adolescent; HIV; sexually transmitted infections; criminalization; policing
6.  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
7.  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
8.  Potential Impact of the US President's Emergency Plan for AIDS Relief on the Tuberculosis/HIV Coepidemic in Selected Sub-Saharan African Countries 
The Journal of Infectious Diseases  2013;208(12):2075-2084.
Background. There are limited data measuring the impact of expanded human immunodeficiency virus (HIV) prevention activities on the tuberculosis epidemic at the country level. Here, we characterized the potential impact of the US President's Emergency Plan for AIDS Relief (PEPFAR) on the tuberculosis epidemic in sub-Saharan Africa.
Methods. We selected 12 focus countries (countries receiving the greatest US government investments) and 29 nonfocus countries (controls). We used tuberculosis incidence and mortality rates and relative risks to compare time periods before and after PEPFAR's inception, and a tuberculosis/HIV indicator to calculate the rate of change in tuberculosis incidence relative to the HIV prevalence.
Results. Comparing the periods before and after PEPFAR's implementation, both tuberculosis incidence and mortality rates have diminished significantly and to a higher degree in focus countries. The relative risk for developing tuberculosis, comparing those with and without HIV, was 22.5 for control and 20.0 for focus countries. In most focus countries, the tuberculosis epidemic is slowing down despite some regions still experiencing an increase in HIV prevalence.
Conclusions. This ecological study showed that PEPFAR had a more consistent and substantial effect on HIV and tuberculosis in focus countries, highlighting the likely link between high levels of HIV investment and broader effects on related diseases such as tuberculosis.
doi:10.1093/infdis/jit406
PMCID: PMC3836466  PMID: 23911712
tuberculosis; HIV; coepidemic; sub-Saharan Africa; PEPFAR; incidence; mortality
9.  Trends in plasma HIV-RNA suppression and antiretroviral resistance in British Columbia, 1997-2010 
Objectives
To examine temporal trends in plasma viral load (pVL) suppression and antiretroviral resistance from 1997-2010 in British Columbia (BC), Canada, and determine characteristics, pVL ranges, and resistance profiles of HIV-positive individuals with unsuppressed pVL in 2010.
Methods
HIV-positive individuals ≥19 years old in the provincial database at the BC Centre for Excellence in HIV/AIDS were included. Virologic suppression was defined as two consecutive pVL <500 copies/mL within each calendar year. Temporal trends were evaluated using the Cochran-Armitage test. Persons with suppressed vs. unsuppressed pVL in 2010 were compared using the Pearson χ2 or Fisher’s exact test (categorical variables) and the Wilcoxon rank-sum test (quantitative variables), including unsuppressed individuals only if they were on antiretroviral therapy (ART) in 2010 or their baseline CD4 count was <350 cells/mm3 or <500 cells/mm3, in separate analyses.
Results
The proportion of individuals with suppressed pVL increased from 24% to 80% (p<0.001). In comparative analyses, individuals with unsuppressed pVL (877 of 6142) were more likely to be female (30% vs. 16%), younger (median 43 vs. 48 years), have injection drug use history (38% vs. 30%), report Aboriginal ancestry (30% vs. 16%), and have hepatitis C co-infection (57% vs. 34%) (all p<0.001). Similar patterns were observed using the <500 cells/mm3 CD4 cut-off. The median pVL of all unsuppressed individuals in 2010 was 12,896 copies/mL (IQR 1,495-47,763).
Conclusions
The proportion of individuals achieving pVL suppression in BC has increased markedly since 1997, however further efforts are needed to maximize the individual and societal benefits of modern ART.
doi:10.1097/QAI.0b013e3182a8efc3
PMCID: PMC4266465  PMID: 23978999
HIV; viral suppression; antiretroviral therapy; treatment as prevention; antiretroviral resistance; Canada
10.  Risk Factors for Progression to Regular Injection Drug Use among Street-Involved Youth in a Canadian Setting 
Drug and alcohol dependence  2013;133(2):10.1016/j.drugalcdep.2013.07.008.
Background
Street-involved youth are at high risk for experimenting with injection drug use; however, little attention has been given to identifying the factors that predict progression to on-going injecting.
Methods
Logistic regression was used to identify factors associated with progression to injecting weekly on a regular basis among a Canadian cohort of street-involved youth.
Results
Among our sample of 405 youth who had initiated injecting at baseline or during study observation, the median age was 22 years (interquartile range [IQR] = 21 – 24), and 72% (293) reported becoming a regular injector at some point after their first injection experience. Of these, the majority (n=186, 63%) reported doing so within a month of initiating injection drug use. In multivariate analysis, the drug used at the first injection initiation event (opiates vs. cocaine vs. methamphetamine vs. other; all p > 0.05) was not associated with progression; however, younger age at first injection (adjusted odds ratio [AOR] =1.13), a history of childhood physical abuse (AOR =1.81), prior regular use of the drug first injected (AOR =1.77), and having a sexual partner present at the first injection event (AOR =2.65) independently predicted progression to regular injecting.
Conclusion
These data highlight how quickly youth progress to become regular injectors after experimentation. Findings indicate that addressing childhood trauma and interventions such as evidence-based youth focused addiction treatment that could prevent or delay regular non-injection drug use, may reduce progression to regular injection drug use among this population.
doi:10.1016/j.drugalcdep.2013.07.008
PMCID: PMC3818386  PMID: 23910434
injection drug use; injection initiation; street-involved youth; injection prevention; physical abuse
11.  Predictors of liver-related death among people who inject drugs in Vancouver, Canada: a 15-year prospective cohort study 
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.
doi:10.7448/IAS.17.1.19296
PMCID: PMC4228046  PMID: 25391765
injection drug use; hepatitis C virus infection; mortality; Canada
12.  The impact of drug use patterns on mortality among polysubstance users in a Canadian setting: a prospective cohort study 
BMC Public Health  2014;14(1):1153.
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.
doi:10.1186/1471-2458-14-1153
PMCID: PMC4246520  PMID: 25377274
Mortality; Injection drug use; Cocaine; Vancouver; Cohort study
13.  How Can We Get Close to Zero? The Potential Contribution of Biomedical Prevention and the Investment Framework towards an Effective Response to HIV 
PLoS ONE  2014;9(11):e111956.
Background
In 2011 an Investment Framework was proposed that described how the scale-up of key HIV interventions could dramatically reduce new HIV infections and deaths in low and middle income countries by 2015. This framework included ambitious coverage goals for prevention and treatment services resulting in a reduction of new HIV infections by more than half. However, it also estimated a leveling in the number of new infections at about 1 million annually after 2015.
Methods
We modeled how the response to AIDS can be further expanded by scaling up antiretroviral treatment (ART) within the framework provided by the 2013 WHO treatment guidelines. We further explored the potential contributions of new prevention technologies: ‘Test and Treat’, pre-exposure prophylaxis and an HIV vaccine.
Findings
Immediate aggressive scale up of existing approaches including the 2013 WHO guidelines could reduce new infections by 80%. A ‘Test and Treat’ approach could further reduce new infections. This could be further enhanced by a future highly effective pre-exposure prophylaxis and an HIV vaccine, so that a combination of all four approaches could reduce new infections to as low as 80,000 per year by 2050 and annual AIDS deaths to 260,000.
Interpretation
In a set of ambitious scenarios, we find that immediate implementation of the 2013 WHO antiretroviral therapy guidelines could reduce new HIV infections by 80%. Further reductions may be achieved by moving to a ‘Test and Treat’ approach, and eventually by adding a highly effective pre-exposure prophylaxis and an HIV vaccine, if they become available.
doi:10.1371/journal.pone.0111956
PMCID: PMC4221192  PMID: 25372770
14.  Self-management of pain among people who inject drugs in Vancouver 
Pain management  2014;4(1):27-35.
SUMMARY
Aims
To evaluate factors and methods associated with self-management of pain among people who inject drugs (IDUs) in Vancouver (Canada).
Patients & methods
This cross-sectional study used bivariate statistics and multivariate logistic regression to analyze self-reported responses among 483 IDUs reporting moderate-to-extreme pain in two prospective cohort studies from 1 December 2012 to 31 May 2013.
Results
Median age was 49.6 years (interquartile range: 43.9–54.6 years), 33.1% of IDUs were female and 97.5% reported self-management of pain. Variables independently and positively associated with self-managed pain included having been refused a prescription for pain medication (adjusted odds ratio: 7.83; 95% CI: 1.64–37.3) and having ever been homeless (adjusted odds ratio: 3.70; 95% CI: 1.00–13.7). Common methods of self-management of pain included injecting heroin (52.7%) and obtaining diverted prescription pain medication from the street (65.0%).
Conclusion
Self-management of pain was common among IDUs who reported moderate-to-extreme pain in this setting, particularly among those who had been refused a prescription for pain medication and those who had ever been homeless. These data highlight the challenges of adequate pain management among IDUs.
doi:10.2217/pmt.13.62
PMCID: PMC3962749  PMID: 24641341
16.  Hepatitis C Viremia and the Risk of Chronic Kidney Disease in HIV-Infected Individuals 
Lucas, Gregory M. | Jing, Yuezhou | Sulkowski, Mark | Abraham, Alison G. | Estrella, Michelle M. | Atta, Mohamed G. | Fine, Derek M. | Klein, Marina B. | Silverberg, Michael J. | Gill, M. John | Moore, Richard D. | Gebo, Kelly A. | Sterling, Timothy R. | Butt, Adeel A. | Kirk, Gregory D. | Benson, Constance A. | Bosch, Ronald J. | Collier, Ann C. | Boswell, Stephen | Grasso, Chris | Mayer, Ken | Hogg, Robert S. | Harrigan, Richard | Montaner, Julio | Cescon, Angela | Brooks, John T. | Buchacz, Kate | Gebo, Kelly A. | Moore, Richard D. | Carey, John T. | Rodriguez, Benigno | Horberg, Michael A. | Silverberg, Michael J. | Horberg, Michael A. | Thorne, Jennifer E. | Goedert, James J. | Jacobson, Lisa P. | Klein, Marina B. | Rourke, Sean B. | Burchell, Ann | Rachlis, Anita R. | Rico, Puerto | Hunter-Mellado, Robert F. | Mayor, Angel M. | Gill, M. John | Deeks, Steven G. | Martin, Jeffrey N. | Patel, Pragna | Brooks, John T. | Saag, Michael S. | Mugavero, Michael J. | Willig, James | Eron, Joseph J. | Napravnik, Sonia | Kitahata, Mari M. | Crane, Heidi M. | Justice, Amy C. | Dubrow, Robert | Fiellin, David | Sterling, Timothy R. | Haas, David | Bebawy, Sally | Turner, Megan | Gange, Stephen J. | Anastos, Kathryn | Moore, Richard D. | Saag, Michael S. | Gange, Stephen J. | Kitahata, Mari M. | McKaig, Rosemary G. | Justice, Amy C. | Freeman, Aimee M. | Moore, Richard D. | Freeman, Aimee M. | Lent, Carol | Kitahata, Mari M. | Van Rompaey, Stephen E. | Crane, Heidi M. | Webster, Eric | Morton, Liz | Simon, Brenda | Gange, Stephen J. | Althoff, Keri N. | Abraham, Alison G. | Lau, Bryan | Zhang, Jinbing | Jing, Jerry | Golub, Elizabeth | Modur, Shari | Hanna, David B. | Rebeiro, Peter | Wong, Cherise | Mendes, Adell
The Journal of Infectious Diseases  2013;208(8):1240-1249.
Background. The role of active hepatitis C virus (HCV) replication in chronic kidney disease (CKD) risk has not been clarified.
Methods. We compared CKD incidence in a large cohort of HIV-infected subjects who were HCV seronegative, HCV viremic (detectable HCV RNA), or HCV aviremic (HCV seropositive, undetectable HCV RNA). Stages 3 and 5 CKD were defined according to standard criteria. Progressive CKD was defined as a sustained 25% glomerular filtration rate (GFR) decrease from baseline to a GFR < 60 mL/min/1.73 m2. We used Cox models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
Results. A total of 52 602 HCV seronegative, 9508 HCV viremic, and 913 HCV aviremic subjects were included. Compared with HCV seronegative subjects, HCV viremic subjects were at increased risk for stage 3 CKD (adjusted HR 1.36 [95% CI, 1.26, 1.46]), stage 5 CKD (1.95 [1.64, 2.31]), and progressive CKD (1.31 [1.19, 1.44]), while HCV aviremic subjects were also at increased risk for stage 3 CKD (1.19 [0.98, 1.45]), stage 5 CKD (1.69 [1.07, 2.65]), and progressive CKD (1.31 [1.02, 1.68]).
Conclusions. Compared with HIV-infected subjects who were HCV seronegative, both HCV viremic and HCV aviremic individuals were at increased risk for moderate and advanced CKD.
doi:10.1093/infdis/jit373
PMCID: PMC3778973  PMID: 23904290
HIV; hepatitis C virus; chronic kidney disease; hepatitis C RNA; cohort study; glomerular filtration rate; injection drug use
17.  PATTERNS OF INJECTION DRUG USE CESSATION DURING AN EXPANSION OF SYRINGE EXCHANGE SERVICES IN A CANADIAN SETTING 
Drug and alcohol dependence  2013;132(3):535-540.
Background
Needle and syringe programmes (NSPs) have been shown to reduce HIV risk among people who inject drugs (IDU). However, concerns remain that NSPs delay injecting cessation.
Methods
Individuals reporting injection drug use in the past six months in the greater Vancouver area were enrolled in the Vancouver Injection Drug Users Study (VIDUS). Annual estimates of the proportion of IDU reporting injecting cessation were generated. Generalized estimating equation (GEE) analysis was used to assess factors associated with injecting cessation during a period of NSP expansion.
Results
Between May 1996 and December 2010, the number of NSP sites in Vancouver increased from 1 to 29 (P < 0.001). The estimated proportion of participants (n = 2,710) reporting cessation increased from 2.4% (95% Confidence Interval [CI]: 0.0% – 7.0%) in 1996 to 47.9% (95% CI: 46.8% – 48.9%) in 2010 (P < 0.001). In a multivariate GEE analysis, the authors observed an association between increasing calendar year and increased likelihood of injecting cessation (Adjusted Odds Ratio = 1.17, 95% CI: 1.15, 1.19, P < 0.001).
Conclusion
The proportion of IDU reporting injecting cessation increased during a period of NSP expansion, implying that increased NSP availability did not delay injection cessation. These results should help inform community decisions on whether to implement NSPs.
doi:10.1016/j.drugalcdep.2013.03.024
PMCID: PMC3762907  PMID: 23642315
injection drug use; cessation; needle exchange programme; Vancouver
18.  HIV: seek, test, treat, and retain 
The “HIV: Seek, Test, Treat, and Retain” session was chaired by Dr. Jacques Normand, the Director of AIDS Research at the U.S. National Institute on Drug Abuse. Dr. Yi-Ming Chen served as the discussant. The three presenters (and their presentation topics) were: Dr. Julio Montaner (Treatment as Prevention—The Key to an AIDS-free Generation), Dr. Chi-Tai Fang (Population-level Effect of Free Access to HAART on Reducing HIV Transmission in Taiwan), and Dr. Zunyou Wu (Challenges in Promoting HIV Test & Treat Strategy in China).
doi:10.1016/j.jfda.2013.09.020
PMCID: PMC4179106  PMID: 25278735
HIV; seek; test; treat; retain
19.  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
20.  TRANSITIONS INTO AND OUT OF HOMELESSNESS AMONG STREET-INVOLVED YOUTH IN A CANADIAN SETTING 
Health & place  2013;23:122-127.
The impact of transitions in housing status among street youth have not been well explored. This study uses a generalized linear mixed effects model to identify factors associated with transitions into and out of homelessness among a prospective cohort of 685 drug-using street-involved youth aged 14–26. In multivariate analysis, high intensity substance use, difficulty accessing addiction treatment, incarceration, sex work, and difficulty accessing housing (all p < 0.05) either significantly facilitated or hindered housing transitions. Findings highlight the importance of external structural factors in shaping youth’s housing status and point to opportunities to improve the housing stability of vulnerable youth.
doi:10.1016/j.healthplace.2013.06.003
PMCID: PMC3758414  PMID: 23838565
Homelessness; drug use; street-youth; addiction treatment; risk behavior; incarceration
21.  Cohort Profile: Longitudinal Investigations into Supportive and Ancillary health services 
The Longitudinal Investigations into Supportive and Ancillary health services (LISA) study is a cohort of people living with HIV/AIDS who have ever accessed anti-retroviral therapy (ART) in British Columbia, Canada. The LISA study was developed to better understand the outcomes of people living with HIV with respect to supportive services use, socio-demographic factors and quality of life. Between July 2007 and January 2010, 1000 participants completed an interviewer-administered questionnaire that included questions concerning medical history, substance use, social and medical support services, food and housing security and other social determinants of health characteristics. Of the 1000 participants, 917 were successfully linked to longitudinal clinical data through the provincial Drug Treatment Program. Within the LISA cohort, 27% of the participants are female, the median age is 39 years and 32% identify as Aboriginal. Knowledge translation activities for LISA include the creation of plain language summaries, internet resources and arts-based engagement activities such as Photovoice.
doi:10.1093/ije/dys035
PMCID: PMC3780992  PMID: 22461127
22.  Client demands for unsafe sex: the socio-economic risk environment for HIV among street and off-street sex workers 
Objective
Among sex workers (SWs) in Vancouver, Canada, this study identified social, drug use, sex work, environmental-structural and client-related factors associated with being offered and accepting more money after clients' demand for sex without a condom.
Design
Cross-sectional study using baseline (February/10-October/11) data from a longitudinal cohort of 510 SWs.
Methods
A two-part multivariable regression model was used to identify factors associated with two separate outcomes: (1) being offered and (2) accepting more money for sex without a condom in the last six months, among those who had been offered more money.
Results
The sample included 490 SWs. In multivariable analysis, being offered more money for sex without a condom was more likely for SWs who used speedballs, had higher average numbers of clients per week, had difficulty accessing condoms and had clients who visited other SWs. Accepting more money for sex without a condom was more likely for SWs self-reporting as a sexual minority and who had experienced client violence and used crystal methamphetamine use less than daily (vs. none), and less likely for SWs who solicited for clients mainly indoors (vs. outdoor/public places).
Conclusions
These results highlight the high demand for sex without a condom by clients of SWs. HIV prevention efforts should shift responsibility toward clients to reduce offers of more money for unsafe sex. Programs that mitigate the social and economic risk environments of SWs alongside the removal of criminal sanctions on sex work to enable condom use within safer indoor work spaces are urgently required.
doi:10.1097/QAI.0b013e3182968d39
PMCID: PMC3706016  PMID: 23614990
condom use; sex workers; Canada; HIV risk; clients
23.  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
24.  Prescription opioid injection and risk of hepatitis C in relation to traditional drugs of misuse in a prospective cohort of street youth 
BMJ Open  2014;4(7):e005419.
Objective
Despite dramatic increases in the misuse of prescription opioids, the extent to which their intravenous injection places drug users at risk of acquiring hepatitis C virus (HCV) remains unclear. We sought to compare risk of HCV acquisition from injection of prescription opioids to that from other street drugs among high-risk street youth.
Design
Prospective cohort study.
Setting
Vancouver, British Columbia, Canada from September 2005 to November 2011.
Participants
The At-Risk Youth Study (ARYS) is a prospective cohort of drug-using adolescents and young adults aged 14–26 years. Participants were recruited through street-based outreach and snowball sampling.
Primary outcome measure
HCV antibody seroconversion, measured every 6 months during follow-up. Risk for seroconversion from injection of prescription opioids was compared with injection of other street drugs of misuse, including heroin, cocaine or crystal methamphetamine, using Cox proportional hazards regression controlling for age, gender and syringe sharing.
Results
Baseline HCV seropositivity was 10.6%. Among 512 HCV-seronegative youth contributing 860.2 person-years of follow-up, 56 (10.9%) seroconverted, resulting in an incidence density of 6.5/100 person-years. In bivariate analyses, prescription opioid injection (HR=3.48; 95% CI 1.57 to 7.70) predicted HCV seroconversion. However, in multivariate modelling, only injection of heroin (adjusted HR=4.56; 95% CI 2.39 to 8.70), cocaine (adjusted HR=1.88; 95% CI 1.00 to 3.54) and crystal methamphetamine (adjusted HR=2.91; 95% CI 1.57 to 5.38) remained independently associated with HCV seroconversion, whereas injection of prescription opioids did not (adjusted HR=0.94; 95% CI 0.40 to 2.21).
Conclusions
Although misuse of prescription opioids is on the rise, traditional street drugs still posed the greatest threat of HCV transmission in this setting. Nonetheless, the high prevalence and incidence of HCV among Canadian street youth underscore the need for evidence-based drug prevention, treatment and harm reduction interventions targeting this vulnerable population.
doi:10.1136/bmjopen-2014-005419
PMCID: PMC4120401  PMID: 25052173
INFECTIOUS DISEASES
25.  Leveraging HIV Treatment to End AIDS, Stop New HIV Infections, and Avoid the Cost of Inaction 
We have the tools at our disposal to significantly bend AIDS-related morbidity and mortality curves and reduce human immunodeficiency virus (HIV) incidence. It is thus essential to redouble our efforts to reach the goal of placing 15 million people on life-saving and -enhancing antiretroviral therapy (ART) by 2015. In reaching this milestone, we can write a new chapter in the history of global health, demonstrating that a robust, multidimensional response can succeed against a complex pandemic that presents as many social and political challenges as it does medical ones. This milestone is also critical to advance our ultimate goal of ending AIDS by maximizing the therapeutic and preventive effects of ART, which translates into a world in which AIDS-related deaths and new HIV infections are exceedingly rare.
doi:10.1093/cid/ciu321
PMCID: PMC4060255  PMID: 24926030
HIV; prevention; testing; treatment; antiretroviral therapy

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