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1.  An update to the HIV-TRePS system: the development of new computational models that do not require a genotype to predict HIV treatment outcomes 
Objectives
The optimal individualized selection of antiretroviral drugs in resource-limited settings is challenging because of the limited availability of drugs and genotyping. Here we describe the development of the latest computational models to predict the response to combination antiretroviral therapy without a genotype, for potential use in such settings.
Methods
Random forest models were trained to predict the probability of a virological response to therapy (<50 copies HIV RNA/mL) following virological failure using the following data from 22 567 treatment-change episodes including 1090 from southern Africa: baseline viral load and CD4 cell count, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. The models were assessed during cross-validation and with an independent global test set of 1000 cases including 100 from southern Africa. The models' accuracy [area under the receiver-operating characteristic curve (AUC)] was evaluated and compared with genotyping using rules-based interpretation systems for those cases with genotypes available.
Results
The models achieved AUCs of 0.79–0.84 (mean 0.82) during cross-validation, 0.80 with the global test set and 0.78 with the southern African subset. The AUCs were significantly lower (0.56–0.57) for genotyping.
Conclusions
The models predicted virological response to HIV therapy without a genotype as accurately as previous models that included a genotype. They were accurate for cases from southern Africa and significantly more accurate than genotyping. These models will be accessible via the online treatment support tool HIV-TRePS and have the potential to help optimize antiretroviral therapy in resource-limited settings where genotyping is not generally available.
doi:10.1093/jac/dkt447
PMCID: PMC3956369  PMID: 24275116
antiretroviral therapy; resource-limited settings; genotyping
2.  The Impact of Engagement in Street-based Income Generation Activities on Stimulant Drug Use Cessation among People who Inject Drugs 
Drug and alcohol dependence  2014;141:58-64.
Background
Despite the growing prevalence of illicit stimulant drug use internationally, and the widespread involvement of people who inject drugs (IDU) within street-based drug markets, little is known about the impact of different types of street-based income generation activities on the cessation of stimulant use among IDU.
Methods
Data were derived from an open prospective cohort of IDU in Vancouver, Canada. We used Kaplan-Meier methods and Cox proportional hazards regression to examine the effect of different types of street-based income generation activities (e.g., sex work, drug dealing, and scavenging) on time to cessation of stimulant use.
Results
Between December, 2005 and November, 2012, 887 IDU who use stimulant drugs (cocaine, crack cocaine, or crystal methamphetamine) were prospectively followed-up for a median duration of 47 months. In Kaplan-Meier analyses, compared to those who did not engage in street-based income generation activities, participants who reported sex work, drug dealing, scavenging, or more than one of these activities were significantly less likely to report stimulant drug use cessation (all p<0.001). When considered as time-updated variables and adjusted for potential confounders in a multivariable model, each type of street-based income generation activity remained significantly associated with a slower time to stimulant drug cessation (all p<0.005).
Conclusions
Our findings highlight the urgent need for strategies to address stimulant dependence, including novel pharmacotherapies. Also important, structural interventions, such as low-threshold employment opportunities, availability of supportive housing, legal reforms regarding drug use, and evidence-based approaches that reduce harm among IDU are urgently required.
doi:10.1016/j.drugalcdep.2014.05.003
PMCID: PMC4090016  PMID: 24909853
people who inject drugs; stimulants; crack cocaine; crystal methamphetamine; drug cessation; street economy
3.  Cohort Profile: Seek and Treat for the Optimal Prevention of HIV/AIDS in British Columbia (STOP HIV/AIDS BC) 
The Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort is a census of all identified HIV-positive individuals in the province of British Columbia. It was formed through the linkage of nine provincial treatment, surveillance and administrative databases. This open cohort allows for bidirectional analyses from 1996 onward and is refreshed annually. Extensive data collection for cohort members includes demographic information, detailed clinical and laboratory data, complete prescription drug use including antiretroviral agents, and information on health service utilization encompassing inpatient and outpatient care, addictions treatment and palliative care. This cohort provides an unprecedented opportunity to evaluate, over an extended time period, patterns and determinants of key outcomes including engagement in the cascade of HIV care from diagnosis to treatment to viral suppression as well as monitoring trends in medical costs, health outcomes and other key healthcare delivery indicators at a population level with wide-ranging, high-quality data. The overall purpose of these activities is to enable the development and implementation of strategically targeted interventions to improve access to testing, care and treatment for all HIV-positive individuals living in British Columbia. As a programme of the Ministry of Health, the STOP HIV/AIDS Evaluation Evaluation Team welcomes input from all stakeholders and possible partners via contact with the Director of Operations for the British Columbia Centre for excellence in HIV AIDS, Ms. Irene Day (iday@cfenet.ubc.ca).
doi:10.1093/ije/dyu070
PMCID: PMC4121558  PMID: 24695113
4.  Complexities of Short-Term Mobility for Sex Work and Migration among Sex Workers: Violence and Sexual Risks, Barriers to Care, and Enhanced Social and Economic Opportunities 
Despite research on the health and safety of mobile and migrant populations in the formal and informal sectors globally, limited information is available regarding the working conditions, health, and safety of sex workers who engage in short-term mobility and migration. The objective of this study was to longitudinally examine work environment, health, and safety experiences linked to short-term mobility/migration (i.e., worked or lived in another city, province, or country) among sex workers in Vancouver, Canada, over a 2.5-year study period (2010–2012). We examined longitudinal correlates of short-term mobility/migration (i.e., worked or lived in another city, province, or country over the 3-year follow-up period) among 646 street and off-street sex workers in a longitudinal community-based study (AESHA). Of 646 sex workers, 10.84 % (n = 70) worked or lived in another city, province, or country during the study. In a multivariate generalized estimating equations (GEE) model, short-term mobility/migration was independently correlated with older age (adjusted odds ratio (AOR) 0.95, 95 % confidence interval (CI) 0.92–0.98), soliciting clients in indoor (in-call) establishments (AOR 2.25, 95 % CI 1.27–3.96), intimate partner condom refusal (AOR 3.00, 1.02–8.84), and barriers to health care (AOR 1.77, 95 % CI 1.08–2.89). In a second multivariate GEE model, short-term mobility for sex work (i.e., worked in another city, province, or country) was correlated with client physical/sexual violence (AOR 1.92, 95 % CI 1.02–3.61). In this study, mobile/migrant sex workers were more likely to be younger, work in indoor sex work establishments, and earn higher income, suggesting that short-term mobility for sex work and migration increase social and economic opportunities. However, mobility and migration also correlated with reduced control over sexual negotiation with intimate partners and reduced health care access, and mobility for sex work was associated with enhanced workplace sexual/physical violence, suggesting that mobility/migration may confer risks through less control over work environment and isolation from health services. Structural and community-led interventions, including policy support to allow for more formal organizing of sex work collectives and access to workplace safety standards, remain critical to supporting health, safety, and access to care for mobile and migrant sex workers.
doi:10.1007/s11524-014-9888-1
PMCID: PMC4134448  PMID: 25055750
Mobility; Migration; Sex workers; HIV; Violence
5.  SUBOPTIMAL PLASMA HIV-1 RNA SUPPRESSION AND ADHERENCE AMONG SEX WORKERS WHO USE ILLICIT DRUGS IN A CANADIAN SETTING: AN OBSERVATIONAL COHORT STUDY 
Sexually transmitted infections  2014;90(5):418-422.
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.
doi:10.1136/sextrans-2013-051408
PMCID: PMC4102614  PMID: 24523347
6.  Life expectancy of HIV-positive individuals on combination antiretroviral therapy in Canada 
BMC Infectious Diseases  2015;15:274.
Background
We sought to evaluate life expectancy and mortality of HIV-positive individuals initiating combination antiretroviral therapy (ART) across Canada, and to consider the potential error introduced by participant loss to follow-up (LTFU).
Methods
Our study used data from the Canadian Observational Cohort (CANOC) collaboration, including HIV-positive individuals aged ≥18 years who initiated ART on or after January 1, 2000. The CANOC collaboration collates data from eight sites in British Columbia, Ontario, and Quebec. We computed abridged life-tables and remaining life expectancies at age 20 and compared outcomes by calendar period and patient characteristics at treatment initiation. To correct for potential underreporting of mortality due to participant LTFU, we conservatively estimated 30 % mortality among participants lost to follow-up.
Results
9997 individuals contributed 49,589 person-years and 830 deaths for a crude mortality rate of 16.7 [standard error (SE) 0.6] per 1000 person-years. When assigning death to 30 % of participants lost to follow-up, we estimated 1170 deaths and a mortality rate of 23.6 [SE 0.7] per 1000 person-years. The crude overall life expectancy at age 20 was 45.2 [SE 0.7] and 37.5 [SE 0.6] years after adjusting for LTFU. In the LTFU-adjusted analysis, lower life expectancy at age 20 was observed for women compared to men (32.4 [SE 1.1] vs. 39.2 [SE 0.7] years), for participants with injection drug use (IDU) history compared to those without IDU history (23.9 [SE 1.0] vs. 52.3 [SE 0.8] years), for participants reporting Aboriginal ancestry compared to those with no Aboriginal ancestry (17.7 [SE 1.5] vs. 51.2 [SE 1.0] years), and for participants with CD4 count <350 cells/μL compared to CD4 count ≥350 cells/μL at treatment initiation (36.3 [SE 0.7] vs. 43.5 [SE 1.3] years). Life expectancy at age 20 in the calendar period 2000–2003 was lower than in periods 2004–2007 and 2008–2012 in the LTFU-adjusted analyses (30.8 [SE 0.9] vs. 38.6 [SE 1.0] and 54.2 [SE 1.4]).
Conclusions
Life expectancy and mortality for HIV-positive individuals receiving ART differ by calendar period and patient characteristics at treatment initiation. Failure to consider LTFU may result in underestimation of mortality rates and overestimation of life expectancy.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-015-0969-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-015-0969-x
PMCID: PMC4504463  PMID: 26183704
Life expectancy; Mortality; HIV; Antiretroviral therapy; CANOC; Canada
7.  Trends in AIDS Deaths, New Infections and ART Coverage in the Top 30 Countries with the Highest AIDS Mortality Burden; 1990–2013 
PLoS ONE  2015;10(7):e0131353.
Background
Antiretroviral therapy (ART) prevents human immunodeficiency virus (HIV) disease progression, mortality and transmission. We assess the impact of expanded HIV treatment for the prevention of Acquired Immunodeficiency Syndrome (AIDS)-related deaths and simulate four treatment scenarios for Nigeria and South Africa.
Methods
For 1990–2013, we used the Joint United Nations Programme on HIV/AIDS (UNAIDS) database to examine trends in AIDS deaths, HIV incidence and prevalence, ART coverage, annual AIDS death rate, AIDS death-to-treatment and HIV infections to treatment ratios for the top 30 countries with the highest AIDS mortality burden and compare them with data from high-income countries. We projected the 1990–2020 AIDS deaths for Nigeria and South Africa using four treatment scenarios: 1) no ART; 2) maintaining current ART coverage; 3) 90% ART coverage based on 2013 World Health Organization (WHO) ART guidelines by 2020; and 4) reaching the United Nations 90-90-90 Target by 2020.
Findings
In 2013, there were 1.3 million (1.1 million–1.6 million) AIDS deaths in the top 30 countries representing 87% of global AIDS deaths. Eight countries accounted for 58% of the global AIDS deaths; Nigeria and South Africa accounted for 27% of global AIDS deaths. The highest death rates per 1000 people living with HIV were in Central African Republic (91), South Sudan (82), Côte d’Ivoire (75), Cameroon (72) and Chad (71), nearly 8–10 times higher than the high-income countries. ART access in 2013 has averted as estimated 1,051,354 and 422,448 deaths in South Africa and Nigeria, respectively. Increasing ART coverage in these two countries to meet the proposed UN 90-90-90 Target by 2020 could avert 2.2 and 1.2 million deaths, respectively.
Interpretation
Over the past decade the expansion of access to ART averted millions of deaths. Reaching the proposed UN 90-90-90 Target by 2020 will prevent additional morbidity, mortality and HIV transmission. Despite progress, high-burden countries will need to accelerate access to ART treatment to avert millions of premature AIDS deaths and new HIV infections.
doi:10.1371/journal.pone.0131353
PMCID: PMC4493077  PMID: 26147987
8.  HEALTH AND SOCIAL HARMS ASSOCIATED WITH CRYSTAL METHAMPHETAMINE USE AMONG STREET-INVOLVED YOUTH IN A CANADIAN SETTING 
Background and objectives
Despite recent increases in crystal methamphetamine use among high-risk populations such as street-involved youth, few prospective studies have examined the health and social outcomes associated with active crystal methamphetamine use.
Methods
We enrolled 1,019 street-involved youth in Vancouver, Canada, in a prospective cohort known as the At-Risk Youth Study (ARYS). Participants were assessed semi-annually and a generalized estimating equation (GEE) logistic regression was used to identify factors independently associated with active crystal methamphetamine use.
Results
Among 1,019 participants recruited into ARYS between 2005 and 2012 the median follow up duration was 17 months, 320 (31.4%) participants were female and 454 (44.6%) had previously used crystal methamphetamine at baseline. In adjusted GEE analyses, active crystal methamphetamine use was independently associated with Caucasian ethnicity (Adjusted Odds Ratio [AOR] = 1.37; 95% Confidence Interval [CI]: 1.04 – 1.81), homelessness (AOR = 1.34; 95% CI: 1.15 – 1.56), injection drug use (AOR = 3.40; 95% CI: 2.76 – 4.19), non-fatal overdose (AOR = 1.46; 95% CI: 1.07 – 2.00), being a victim of violence (AOR = 1.19; 95% CI: 1.02 – 1.38), involvement in sex work (AOR = 1.39; 95% CI: 1.03 – 1.86) and drug dealing (AOR = 1.60; 95% CI: 1.35 – 1.90).
Discussion and conclusions
Prevalence of crystal methamphetamine use was high in this setting and active use was independently associated with a range of serious health and social harms.
Scientific Significance
Evidence-based strategies to prevent and treat crystal methamphetamine use are urgently needed.
doi:10.1111/j.1521-0391.2014.12123.x
PMCID: PMC4072738  PMID: 24628742
crystal methamphetamin; youth; injection drug use; social harm; homelessness
9.  Global Response to HIV: Treatment as Prevention, or Treatment for Treatment? 
The concept of “treatment as prevention” has emerged as a means to curb the global HIV epidemic. There is, however, still ongoing debate about the evidence on when to start antiretroviral therapy in resource-poor settings. Critics have brought forward multiple arguments against a “test and treat” approach, including the potential burden of such a strategy on weak health systems and a presumed lack of scientific support for individual patient benefit of early treatment initiation. In this article, we highlight the societal and individual advantages of treatment as prevention in resource-poor settings. We argue that the available evidence renders the discussion on when to start antiretroviral therapy unnecessary and that, instead, efforts should be aimed at offering treatment as soon as possible.
doi:10.1093/cid/ciu267
PMCID: PMC4141497  PMID: 24926037
treatment as prevention; antiretroviral therapy; HIV-1; resource-limited settings
12.  Compulsory drug detention exposure is associated with not receiving antiretroviral treatment among people who inject drugs in Bangkok, Thailand: a cross-sectional study 
Background
Thailand has experienced a longstanding epidemic of HIV among people who inject drugs (PWID). However, antiretroviral treatment (ART) coverage among HIV-positive PWID has historically remained low. While ongoing drug law enforcement involving periodic police crackdowns is known to increase the risk of HIV transmission among Thai PWID, the impact of such drug policy approaches on the ART uptake has been understudied. Therefore, we sought to identify factors associated with not receiving ART among HIV-positive PWID in Bangkok, Thailand, with a focus on factors pertaining to drug law enforcement.
Methods
Data were collected from a community-recruited sample of HIV-positive PWID in Bangkok who participated in the Mitsampan Community Research Project between June 2009 and October 2011. We identified factors associated with not receiving ART at the time of interview using multivariate logistic regression.
Results
In total, 128 HIV-positive PWID participated in this study, with 58 (45.3%) reporting not receiving ART at the time of interview. In multivariate analyses, completing less than secondary education (adjusted odds ratio [AOR]: 3.32 ; 95% confidence interval [CI]: 1.48 – 7.45), daily midazolam injection (AOR: 3.22, 95% CI: 1.45 – 7.15) and exposure to compulsory drug detention (AOR: 3.36, 95% CI: 1.01 – 11.21) were independently and positively associated with not receiving ART. Accessing peer-based healthcare information or support services was independently and positively associated with receiving ART (AOR: 0.21, 95% CI: 0.05 – 0.84).
Conclusions
Approximately half of our study group of HIV-positive PWID reported not receiving ART at the time of interview. Daily midazolam injectors, those with lower education attainment, and individuals who had been in compulsory drug detention were more likely to be non-recipients of ART whereas those who accessed peer-based healthcare-related services were more likely to receive ART. These findings suggest a potentially adverse impact of compulsory drug detention and highlight the need to expand interventions to facilitate access to ART among HIV-positive PWID in this setting.
doi:10.1186/s13011-015-0013-6
PMCID: PMC4435625  PMID: 25943881
ART; Injection drug use; Compulsory drug detention; Peer-based intervention; Thailand
13.  Income Level and Drug Related Harm among People Who Use Injection Drugs in a Canadian Setting 
Background
Higher income is generally associated with better health outcomes; however, among people who inject drugs (IDU) income generation frequently involves activities, such as sex work and drug dealing, which pose significant health risks. Therefore, we sought to examine the relationship between level of income and specific drug use patterns and related health risks.
Methods
This study involved IDU participating in a prospective cohort study in Vancouver, Canada. Monthly income was categorized based on non-fixed quartiles at each follow-up with the lowest level serving as the reference category in generalized linear mixed-effects regression.
Results
Among our sample of 1,032 IDU, the median average monthly income over the study follow-up was $1050 [Interquartile range=785–2000]. In multivariate analysis, the highest income category was significantly associated with sex work (Adjusted Odds Ratio [AOR]=7.65), drug dealing (AOR=5.06), daily heroin injection (AOR=2.97), daily cocaine injection (AOR=1.65), daily crack smoking (AOR=2.48), binge drug use (AOR=1.57) and unstable housing (AOR=1.67). The high income category was negatively associated with being female (AOR=0.61) and accessing addiction treatment (AOR=0.64), (all p < 0.05). In addition, higher income was strongly associated with higher monthly expenditure on drugs (>$400) (OR=97.8).
Conclusion
Among IDU in Vancouver, average monthly income levels were low and higher total monthly income was linked to high-risk income generation strategies as well as a range of drug use patterns characteristic of higher intensity addiction and HIV risk. These findings underscore the need for interventions that provide economic empowerment and address high intensity addiction, especially for female IDU.
doi:10.1016/j.drugpo.2013.11.011
PMCID: PMC4040344  PMID: 24380808
Canada; Injection drug use; Income generation; Sex work; Drug dealing
14.  The Impact of Implementing a Test, Treat and Retain HIV Prevention Strategy in Atlanta among Black Men Who Have Sex with Men with a History of Incarceration: A Mathematical Model 
PLoS ONE  2015;10(4):e0123482.
Background
Annually, 10 million adults transition through prisons or jails in the United States (US) and the prevalence of HIV among entrants is three times higher than that for the country as a whole. We assessed the potential impact of increasing HIV Testing/Treatment/Retention (HIV-TTR) in the community and within the criminal justice system (CJS) facilities, coupled with sexual risk behavior change, focusing on black men-who-have-sex-with-men, 15–54 years, in Atlanta, USA.
Methods
We modeled the effect of a HIV-TTR strategy on the estimated cumulative number of new (acquired) infections and mortality, and on the HIV prevalence at the end of ten years. We additionally assessed the effect of increasing condom use in all settings.
Results
In the Status Quo scenario, at the end of 10 years, the cumulative number of new infections in the community, jail and prison was, respectively, 9246, 77 and 154 cases; HIV prevalence was 10815, 69 and 152 cases, respectively; and the cumulative number of deaths was 2585, 18 and 34 cases, respectively. By increasing HIV-TTR coverage, the cumulative number of new infections could decrease by 15% in the community, 19% in jail, and 8% in prison; HIV prevalence could decrease by 8%, 9% and 7%, respectively; mortality could decrease by 20%, 39% and 18%, respectively. Based on the model results, we have shown that limited use and access to condoms have contributed to the HIV incidence and prevalence in all settings.
Conclusions
Aggressive implementation of a CJS-focused HIV-TTR strategy has the potential to interrupt HIV transmission and reduce mortality, with benefit to the community at large. To maximize the impact of these interventions, retention in treatment, including during the period after jail and prison release, and increased condom use was vital for decreasing the burden of the HIV epidemic in all settings.
doi:10.1371/journal.pone.0123482
PMCID: PMC4408043  PMID: 25905725
15.  Drug use patterns associated with risk of non-adherence to antiretroviral therapy among HIV-positive illicit drug users in a Canadian setting: a longitudinal analysis 
BMC Infectious Diseases  2015;15:193.
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.
doi:10.1186/s12879-015-0913-0
PMCID: PMC4411762  PMID: 25927573
HIV; Antiretroviral therapy; Illicit drug use; Heroin; Cocaine; Adherence
16.  Absolute Leukocyte Telomere Length in HIV-Infected and Uninfected Individuals: Evidence of Accelerated Cell Senescence in HIV-Associated Chronic Obstructive Pulmonary Disease 
PLoS ONE  2015;10(4):e0124426.
Combination antiretroviral therapy (cART) has extended the longevity of human immunodeficiency virus (HIV)-infected individuals. However, this has resulted in greater awareness of age-associated diseases such as chronic obstructive pulmonary disease (COPD). Accelerated cellular senescence may be responsible, but its magnitude as measured by leukocyte telomere length is unknown and its relationship to HIV-associated COPD has not yet been established. We measured absolute telomere length (aTL) in peripheral leukocytes from 231 HIV-infected adults. Comparisons were made to 691 HIV-uninfected individuals from a population-based sample. Subject quartiles of aTL were assessed for relationships with measures of HIV disease severity, airflow obstruction, and emphysema severity on computed tomographic (CT) imaging. Multivariable regression models identified factors associated with shortened aTL. Compared to HIV-uninfected subjects, the mean aTL in HIV-infected patients was markedly shorter by 27 kbp/genome (p<0.001); however, the slopes of aTL vs. age were not different (p=0.469). Patients with longer known durations of HIV infection (p=0.019) and lower nadir CD4 cell counts (p=0.023) had shorter aTL. Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049). HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.
doi:10.1371/journal.pone.0124426
PMCID: PMC4401786  PMID: 25885433
17.  Disparities in the Quality of HIV Care When Using US Department of Health and Human Services Indicators 
Althoff, Keri N. | Rebeiro, Peter | Brooks, John T. | Buchacz, Kate | Gebo, Kelly | Martin, Jeffrey | Hogg, Robert | Thorne, Jennifer E. | Klein, Marina | Gill, M. John | Sterling, Timothy R. | Yehia, Baligh | Silverberg, Michael J. | Crane, Heidi | Justice, Amy C. | Gange, Stephen J. | Moore, Richard | Kitahata, Mari M. | Horberg, Michael A. | Kirk, Gregory D. | Benson, Constance A. | Bosch, Ronald J. | Collier, Ann C. | Boswell, Stephen | Grasso, Chris | Mayer, Kenneth H. | Hogg, Robert S. | Richard Harrigan, P. | Montaner, Julio SG | Cescon, Angela | Samji, Hasina | Brooks, John T. | Buchacz, Kate | Gebo, Kelly A. | Moore, Richard D. | Moore, Richard D. | Carey, John T. | Horberg, Michael A. | Silverberg, Michael J. | Thorne, Jennifer E. | Goedert, James J. | Jacobson, Lisa P. | Klein, Marina B. | Rourke, Sean B. | Burchell, Ann N. | Rachlis, Anita R. | Hunter-Mellado, Robert F. | Mayor, Angel M. | Gill, M.John | Deeks, Steven G. | Martin, Jeffrey N. | 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. | Althoff, Keri N. | 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. | Morton, Liz | McReynolds, Justin | Lober, William B. | 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
We estimated US Department of Health and Human Services (DHHS)–approved human immunodeficiency virus (HIV) indicators. Among patients, 71% were retained in care, 82% were prescribed treatment, and 78% had HIV RNA ≤200 copies/mL; younger adults, women, blacks, and injection drug users had poorer outcomes. Interventions are needed to reduce retention- and treatment-related disparities.
doi:10.1093/cid/ciu044
PMCID: PMC3967825  PMID: 24463281
HIV; quality of care; retention in care; antiretroviral therapy; HIV RNA suppression
18.  Generational Sex And HIV Risk Among Indigenous Women In A Street-Based Urban Canadian Setting 
Culture, health & sexuality  2014;16(4):440-452.
In Canada, indigenous women are overrepresented among new HIV infections and street-based sex workers. Scholars suggest that Aboriginal women’s HIV risk stems from intergenerational effects of colonisation and racial policies. This research examined generational sex work involvement among Aboriginal and non-Aboriginal women and the effect on risk for HIV acquisition. The sample included 225 women in street-based sex work and enrolled in a community-based prospective cohort, in partnership with local sex work and Aboriginal community partners. Bivariate and multivariate logistic regression modeled an independent relationship between Aboriginal ancestry and generational sex work; and the impact of generational sex work on HIV infection among Aboriginal sex workers. Aboriginal women (48%) were more likely to be HIV-positive, with 34% living with HIV compared to 24% non-Aboriginal. In multivariate logistic regression model, Aboriginal women remained 3 times more likely to experience generational sex work (aOR:2.97; 95%CI:1.5,5.8). Generational sex work was significantly associated with HIV (aOR=3.01, 95%CI: 1.67–4.58) in a confounder model restricted to Aboriginal women. High prevalence of generational sex work among Aboriginal women and 3-fold increased risk for HIV infection are concerning. Policy reforms and community-based, culturally safe and trauma informed HIV prevention initiatives are required for Indigenous sex workers.
doi:10.1080/13691058.2014.888480
PMCID: PMC4038328  PMID: 24654881
Canada; Indigenous ancestry; women; sex work; HIV/AIDS
19.  RELATIONSHIP BETWEEN HUNGER, ADHERENCE TO ANTIRETROVIRAL THERAPY AND PLASMA HIV RNA SUPPRESSION AMONG HIV-POSITIVE ILLICIT DRUG USERS IN A CANADIAN SETTING 
AIDS care  2013;26(4):459-465.
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.
doi:10.1080/09540121.2013.832724
PMCID: PMC4064571  PMID: 24015838
HIV; antiretroviral therapy; plasma viral load suppression; food security; hunger; adherence
20.  Denial of pain medication by health care providers predicts in-hospital illicit drug use among individuals who use illicit drugs 
People who use illicit drugs are at risk for related health complications, and may rely more heavily on emergency departments and acute care centres for their health care needs. Health care workers may be hesitant to prescribe pain medication to these individuals due to fear of addiction and suspicion of drug-seeking behaviour. Accordingly, the aim of this study was to assess the relationship between having ever been denied pain medication and having reported using illicit drugs in a Vancouver (British Columbia) cohort of illicit drug users.
BACKGROUND:
Undertreated pain is common among people who use illicit drugs (PWUD), and can often reflect the reluctance of health care providers to provide pain medication to individuals with substance use disorders.
OBJECTIVE:
To investigate the relationship between having ever been denied pain medication by a health care provider and having ever reported using illicit drugs in hospital.
METHODS:
Data were derived from participants enrolled in two Canadian prospective cohort studies between December 2012 and May 2013. Using bivariable and multivariable logistic regression analyses, the relationship between having ever been denied pain medication by a health care provider and having ever reported using illicit drugs in hospital was examined.
RESULTS:
Among 1053 PWUD who had experienced ≥1 hospitalization, 452 (44%) reported having ever used illicit drugs while in hospital and 491 (48%) reported having ever been denied pain medication. In a multivariable model adjusted for confounders, having been denied pain medication was positively associated with having used illicit drugs in hospital (adjusted OR 1.46 [95% CI 1.14 to 1.88]).
CONCLUSIONS:
The results of the present study suggest that the denial of pain medication is associated with the use of illicit drugs while hospitalized. These findings raise questions about how to appropriately manage addiction and pain among PWUD and indicate the potential role that harm reduction programs may play in hospital settings.
PMCID: PMC4391443  PMID: 25562839
Addiction; Canada; Drug use; Health services; Pain management
21.  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
22.  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
23.  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
24.  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
25.  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

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