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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 
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.
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.
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.
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.
PMCID: PMC3956369  PMID: 24275116
antiretroviral therapy; resource-limited settings; genotyping
2.  Improvements in HIV treatment outcomes among indigenous and non-indigenous people who use illicit drugs in a Canadian setting 
In many settings worldwide, members of indigenous groups experience a disproportionate burden of HIV. In Canada, there is an urgent need to improve HIV treatment outcomes for indigenous people living with HIV (IPLWH), to not only reduce HIV/AIDS-associated morbidity and mortality but also curb elevated rates of viral transmission. Thus, by comparing indigenous and non-indigenous participants in an ongoing longitudinal cohort of HIV-positive people who use illicit drugs, we sought to investigate longitudinal changes in three HIV treatment indicators for IPLWH who use illicit drugs during a community-wide treatment-as-prevention (TasP) initiative in British Columbia, Canada.
We used data from the ACCESS study, an ongoing observational prospective cohort of HIV-positive illicit drug users recruited from community settings in Vancouver, British Columbia. Cohort data are linked to comprehensive retrospective and prospective clinical records in a setting of no-cost HIV/AIDS treatment and care. We used multivariable generalized estimating equations (GEE) to evaluate longitudinal changes in the proportion of participants with exposure to antiretroviral therapy (ART) in the previous 180 days, optimal adherence to ART (i.e. ≥95% vs. <95%) and non-detectable HIV-1 RNA viral load (VL <50 copies/mL plasma).
Between 2005 and 2014, 845 individuals were recruited, including 326 (39%) self-reporting any indigenous ancestry, and contributed 6732 interviews and 13,495 VL measurements. Among indigenous participants, the proportion with recent ART increased from 51 to 94% and non-detectable VL from 23 to 65%. In multivariable models, later interview period was positively associated with recent ART (adjusted odds ratio (AOR)=1.16 per interview period, 95% confidence interval (CI): 1.11 to 1.20) and non-detectable VL (AOR=1.07, 95% CI: 1.04 to 1.10). In adjusted models comparing indigenous and non-indigenous participants, we did not observe differences between the two groups (all p>0.1).
In this large and long-term study involving community-recruited HIV-positive illicit drug users, we observed a substantial and increasing proportion of indigenous participants reach several important thresholds in HIV care at rates indistinguishable from non-indigenous participants. The current findings highlight the important role of TasP on vulnerable populations in this setting and contribute to the evidence base supporting the immediate scale-up of ART to address HIV/AIDS-associated morbidity, mortality and viral transmission.
PMCID: PMC4837333  PMID: 27094914
HIV; AIDS; indigenous; highly active antiretroviral therapy; HAART; plasma HIV-1 RNA viral load; treatment-as-prevention
3.  Associations Between Childhood Trauma and Non-Fatal Overdose Among People Who Inject Drugs 
Addictive behaviors  2014;43:83-88.
Although people who inject drugs (IDU) remain at a high risk of accidental overdose, interventions that address overdose remain limited. Accordingly there is a continuing need to identify psychological and social factors that shape overdose risk. Despite being reported frequently among IDU, childhood trauma has received little attention as a potential risk factor for overdose. This study aims to evaluate relationships between non-fatal overdose and five forms of childhood maltreatment among a cohort of IDU in Vancouver, Canada.
Data was obtained from two prospective cohorts of IDU between December 2005 and May 2013. Multivariate generalized estimating equations (GEE) were used to explore relationships between five forms of childhood trauma and non-fatal overdose, adjusting for potential confounders.
During the study period, 1697 IDU, including 552 (32.5%) women, were followed. At baseline, 1136 (67.0%) participants reported at least one form of childhood trauma, while 4–9% reported a non-fatal overdose at each semi-annual follow-up. In multivariate analyses, physical [adjusted odds ratio (AOR): 1.36, 95% confidence interval (CI): 1.08–1.71], sexual (AOR: 1.48, CI: 1.17–1.87), and emotional abuse (AOR: 1.54, CI: 1.22–1.93) and physical neglect (AOR: 1.28, CI: 1.01–1.62) were independently associated with non-fatal overdose (all p < 0.05).
Childhood trauma was common among participants, and reporting an experience of trauma was positively associated with non-fatal overdose. These findings highlight the need to provide intensive overdose prevention to trauma survivors and to incorporate screening for childhood trauma into health and social programs tailored to IDU.
PMCID: PMC4304975  PMID: 25588793
Childhood abuse; Childhood neglect; Childhood maltreatment; Injection drug use; Non-fatal overdose
4.  Pregnancy intentions among female sex workers: Recognising their rights and wants as mothers 
To better understand the prevalence and correlates of pregnancy intentions among female sex workers (FSWs).
Cross-sectional analysis using data from an open prospective cohort of street and off-street FSWs in Vancouver, Canada, in partnership with local sex work and community agencies.
FSWs were recruited through outreach to street and off-street locations (e.g., massage parlours, micro-brothels) and completed interviewer-administered questionnaires and HIV/STI testing. Bivariable and multivariable logistic regression was used to evaluate correlates of pregnancy intention, based on a “yes” versus “no” response to “are you planning on have any (any more) children in the future?”.
Of the 510 women, 394 (77.3%) reported prior pregnancy, with 140 (27.5%) of the entire sample reporting positive pregnancy intentions. 35.3% were Caucasian, and 26.3% were Asian/visible minority, with no differences in pregnancy intention by ethnicity or HIV status. 38.4% reported Canadian Aboriginal ancestry. In our final multivariable model, servicing clients in formal indoor settings, inconsistent condom use by clients, younger age, and intimate partner violence (IPV) were associated with pregnancy intention.
FSWs may have pregnancy intention levels similar to that of women in other occupations. Policy changes are needed to improve FSWs’ access to integrated HIV and reproductive health services and harm reduction services, particularly for FSWs experiencing IPV.
PMCID: PMC4711362  PMID: 25056256
pregnancy intentions; reproductive health; contraception; sex work; HIV; fertility; reproductive rights
5.  The Impact of Clinical, Demographic and Risk Factors on Rates of HIV Transmission: A Population-based Phylogenetic Analysis in British Columbia, Canada 
The Journal of Infectious Diseases  2014;211(6):926-935.
Background. The diversification of human immunodeficiency virus (HIV) is shaped by its transmission history. We therefore used a population based province wide HIV drug resistance database in British Columbia (BC), Canada, to evaluate the impact of clinical, demographic, and behavioral factors on rates of HIV transmission.
Methods. We reconstructed molecular phylogenies from 27 296 anonymized bulk HIV pol sequences representing 7747 individuals in BC—about half the estimated HIV prevalence in BC. Infections were grouped into clusters based on phylogenetic distances, as a proxy for variation in transmission rates. Rates of cluster expansion were reconstructed from estimated dates of HIV seroconversion.
Results. Our criteria grouped 4431 individuals into 744 clusters largely separated with respect to risk factors, including large established clusters predominated by injection drug users and more-recently emerging clusters comprising men who have sex with men. The mean log10 viral load of an individual's phylogenetic neighborhood (composed of 5 other individuals with shortest phylogenetic distances) increased their odds of appearing in a cluster by >2-fold per log10 viruses per milliliter.
Conclusions. Hotspots of ongoing HIV transmission can be characterized in near real time by the secondary analysis of HIV resistance genotypes, providing an important potential resource for targeting public health initiatives for HIV prevention.
PMCID: PMC4351365  PMID: 25312037
molecular epidemiology; human immunodeficiency virus (HIV); phylogenetic clustering; transmission network; injection drug use; men who have sex with men (MSM)
6.  End-Stage Renal Disease Among HIV-Infected Adults in North America 
Abraham, Alison G. | Althoff, Keri N. | Jing, Yuezhou | Estrella, Michelle M. | Kitahata, Mari M. | Wester, C. William | Bosch, Ronald J. | Crane, Heidi | Eron, Joseph | Gill, M. John | Horberg, Michael A. | Justice, Amy C. | Klein, Marina | Mayor, Angel M. | Moore, Richard D. | Palella, Frank J. | Parikh, Chirag R. | Silverberg, Michael J. | Golub, Elizabeth T. | Jacobson, Lisa P. | Napravnik, Sonia | Lucas, Gregory M. | 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. | Moore, Richard D. | Carey, John T. | Rodriguez, Benigno | Horberg, Michael A. | Silverberg, Michael J. | Thorne, Jennifer E. | Goedert, James J. | Jacobson, Lisa P. | Klein, Marina B. | Rourke, Sean B. | Burchell, Ann | 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. | Althoff, Keri N. | 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
Human immunodeficiency virus-infected individuals have benefited from improved viral suppression, but a discrepancy in end-stage renal disease risk between black and nonblack HIV-infected persons remains, in part due to continued disparities in antiretroviral use and viral suppression, and higher rates of comorbidities.
Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks.
Methods. Using data from the North American AIDS Cohort Collaboration for Research and Design from January 2000 to December 2009, we validated 286 incident ESRD cases using abstracted medical evidence of dialysis (lasting >6 months) or renal transplant. A total of 38 354 HIV-infected adults aged 18–80 years contributed 159 825 person-years (PYs). Age- and sex-standardized incidence ratios (SIRs) were estimated by race. Poisson regression was used to identify predictors of ESRD.
Results. HIV-infected ESRD cases were more likely to be of black race, have diabetes mellitus or hypertension, inject drugs, and/or have a prior AIDS-defining illness. The overall SIR was 3.2 (95% confidence interval [CI], 2.8–3.6) but was significantly higher among black patients (4.5 [95% CI, 3.9–5.2]). ESRD incidence declined from 532 to 303 per 100 000 PYs and 138 to 34 per 100 000 PYs over the time period for blacks and nonblacks, respectively, coincident with notable increases in both the prevalence of viral suppression and the prevalence of ESRD risk factors including diabetes mellitus, hypertension, and hepatitis C virus coinfection.
Conclusions. The risk of ESRD remains high among HIV-infected individuals in care but is declining with improvements in virologic suppression. HIV-infected black persons continue to comprise the majority of cases, as a result of higher viral loads, comorbidities, and genetic susceptibility.
PMCID: PMC4357817  PMID: 25409471
end-stage renal disease (ESRD); chronic kidney disease (CKD); HIV infection/AIDS; HIV/AIDS; glomerular filtration rate (GFR)
7.  Trends in AIDS incidence and AIDS-related mortality in British Columbia between 1981 and 2013 
The lancet. HIV  2015;2(3):e92-e97.
Appropriate use of highly active antiretroviral therapy (HAART) can markedly decrease the risk of progression to acquired immunodeficiency syndrome (AIDS) and of premature mortality. We aimed to characterize the trends between 1981 and 2013 in AIDS-defining illnesses (ADIs) and in the number AIDS-related deaths in British Columbia (BC), Canada.
We included data of 3550 HIV-positive individuals, aged 19 years or older, from different administrative databases in BC. We estimated the relative risk of developing an ADI over time using a Negative Binomial model, and we investigated trends in the percentage of all deaths associated with AIDS using generalized additive models.
The number of ADIs has decreased dramatically to its lowest level in 2013. The peak of the AIDS epidemic in BC happened in 1994 with 696 ADIs being reported (rate 42 ADIs per 100 person-years). Since 1997, the number of ADIs decreased from 253 (rate 7 per 100 person-years) to 84 cases in 2013 (rate 1 per 100 person-years) (p-value equals to zero for the trend in the number of ADIs). We have also shown that out of 22 ADIs considered, only PCP maintained its prominent ranking (albeit with much reduced overall prevalence). Finally, we observed that over time very few deaths were related to AIDS-related causes, especially in the most recent years.
We showed that the number of new ADIs and AIDS-related mortality have been decreasing rapidly over time in BC. These results provide further evidence that integrated comprehensive free programs that facilitate testing, and deliver treatment and care to this population can be effective in markedly decreasing AIDS-related morbidity and mortality, thus suggesting that controlling and eventually ending AIDS is possible.
The British Columbia Ministry of Health, the US National Institutes of Health, the US National Institute on Drug Abuse, the Canadian Institutes of Health Research, and the Michael Institute for Health Research.
PMCID: PMC4357843  PMID: 25780802
8.  High-intensity cannabis use associated with lower plasma HIV-1 RNA viral load among recently-infected people who use injection drugs 
Drug and alcohol review  2014;34(2):135-140.
Introduction and Aims
Cannabis use is common among people who are living with HIV/AIDS. While there is growing pre-clinical evidence of the immunomodulatory and anti-viral effects of cannabinoids, their possible effects on HIV disease parameters in humans is largely unknown. Thus, we sought to investigate the possible effects of cannabis use on plasma HIV-1 RNA viral loads among recently-seroconverted illicit drug users.
Design and Methods
We used data from two linked longitudinal observational cohorts of people who use injection drugs. Using multivariable linear mixed-effects modeling, we analysed the relationship between pVL and high-intensity cannabis use among participants who seroconverted following recruitment.
Between May, 1996 and March, 2012, 88 individuals seroconverted after recruitment and were included in these analyses. Median pVL in the first 365 days among all seroconverters was 4.66 log10 c/mL. In a multivariable model, at least daily cannabis use was associated with 0.51 log10 c/mL lower pVL (β = −0.51, Standard Error = 0.170, p-value = 0.003).
Consistent with the findings from recent in vitro and in vivo studies, including one conducted among lentiviral-infected primates, we observed a strong association between cannabis use and lower pVL following seroconversion among illicit drug-using participants.
Our findings support the further investigation of the immunomodulatory or anti-viral effects of cannabinoids among individuals living with HIV/AIDS.
PMCID: PMC4363114  PMID: 25389027
Plasma HIV-1 RNA viral load; cannabis; cannabinoids; HIV infection; disease progression
9.  Denial of Prescription Analgesia Among People Who Inject Drugs in a Canadian Setting 
Drug and alcohol review  2014;34(2):221-228.
Introduction and Aims
Despite the high prevalence of pain among people who inject drugs (PWID), clinicians may be reluctant to prescribe opioid-based analgesia to those with a history of drug use or addiction. We sought to examine the prevalence and correlates of PWID reporting being denied prescription analgesia (PA). We also explored reported reasons for and actions taken after being denied PA.
Design and Methods
Using data from two prospective cohort studies of PWID in Vancouver, Canada, multivariate logistic regression was used to identify the prevalence and correlates of reporting being denied PA. Descriptive statistics were used to characterize reasons for denials and subsequent actions.
Approximately two thirds (66.5%) of our sample of 462 active PWID reported having ever been denied PA. We found that reporting being denied PA was significantly and positively associated with having ever been enrolled in methadone maintenance treatment (MMT) (adjusted odds ratio [AOR]=1.76, 95%CI: 1.11–2.80) and daily cocaine injection (AOR=2.38, 95%CI: 1.00–5.66). The most commonly reported reason for being denied PA was being accused of drug-seeking (44.0%). Commonly reported actions taken after being denied PA included buying the requested medication off the street (40.1%) or obtaining heroin to treat pain (32.9%)
Discussion and Conclusions
These findings highlight the clinical challenges of addressing perceived pain control needs and the need for strategies to prevent high-risk methods of self-managing pain, such as obtaining diverted medications or illicit substances for pain. Such strategies may include integrated pain management guidelines within MMT and other substance use treatment programs.
PMCID: PMC4657858  PMID: 25521168
pain; prescription opioids; diversion; drug seeking; methadone
10.  Cohort Profile: HAART Observational Medical Evaluation and Research (HOMER) Cohort 
Since 1986, antiretroviral therapy (ART) has been available free of charge to individuals living with HIV in British Columbia (BC), Canada, through the BC Centre of Excellence in HIV/AIDS (BC-CfE) Drug Treatment Program (DTP). The Highly Active Antiretroviral Therapy (HAART) Observational Medical Evaluation and Research (HOMER) cohort was established in 1996 to maintain a prospective record of clinical measurements and medication profiles of a subset of DTP participants initiating HAART in BC. This unique cohort provides a comprehensive data source to investigate mortality, prognostic factors and treatment response among people living with HIV in BC from the inception of HAART. Currently over 5000 individuals are enrolled in the HOMER cohort. Data captured include socio-demographic characteristics (e.g. sex, age, ethnicity, health authority), clinical variables (e.g. CD4 cell count, plasma HIV viral load, AIDS-defining illness, hepatitis C co-infection, mortality) and treatment variables (e.g. HAART regimens, date of treatment initiation, treatment interruptions, adherence data, resistance testing). Research findings from the HOMER cohort have featured in numerous high-impact peer-reviewed journals. The HOMER cohort collaborates with other HIV cohorts on both national and international scales to answer complex HIV-specific research questions, and welcomes input from external investigators regarding potential research proposals or future collaborations. For further information please contact the principal investigator, Dr Robert Hogg (
PMCID: PMC4339756  PMID: 24639444
HIV; highly active antiretroviral therapy; cohort studies; database; Canada
Current HIV/AIDS reports  2013;10(4):398-407.
An emerging body of evidence suggests that intergenerational sexual partnerships may increase risk of HIV acquisition among young men who have sex with men (YMSM). However, no studies have comprehensively evaluated literature in this area. We applied a scoping review methodology to explore the relationships between age mixing, HIV risk behavior, and HIV seroconversion among YMSM. This study identified several individual, micro-, and meso-system factors influencing HIV risk among YMSM in the context of intergenerational relationships: childhood maltreatment, coming of age and sexual identity, and substance use (individual-level factors); family and social support, partner characteristics, intimate partner violence, connectedness to gay community (micro-system factors); and race/ethnicity, economic disparity, and use of the Internet (meso-system factors). These thematic groups can be used to frame future research on the role of age-discrepant relationships on HIV risk among YMSM, and to enhance public health HIV education and prevention strategies targeting this vulnerable population.
PMCID: PMC4727934  PMID: 24272070
young men who have sex with men (YMSM); HIV seroconversion; HIV risk intergenerational sex; age mixing
12.  Inability to access addiction treatment predicts injection initiation among street-involved youth in a Canadian setting 
Preventing injection drug use among vulnerable youth is critical for reducing serious drug-related harms. Addiction treatment is one evidence-based intervention to decrease problematic substance use; however, youth frequently report being unable to access treatment services and the impact of this on drug use trajectories remains largely unexplored. This study examines the relationship between being unable to access addiction treatment and injection initiation among street-involved youth.
Data were derived from the At-Risk Youth Study (ARYS), a prospective cohort of street-involved youth aged 14–26 who use illicit drugs, from September 2005 to May 2014. An extended Cox model with time-dependent variables was used to identify factors independently associated with injection initiation.
Among 462 participants who were injection naïve at baseline, 97 (21 %) initiated injection drug use over study follow-up and 129 (28 %) reported trying but being unable to access addiction treatment in the previous 6 months at some point during the study period. The most frequently reported reason for being unable to access treatment was being put on a wait list. In a multivariable Cox regression analysis, being unable to access addiction treatment remained independently associated with a more rapid rate of injection initiation (Adjusted Hazard Ratio =2.02; 95 % Confidence Interval: 1.12–3.62), after adjusting for potential confounders.
Inability to access addiction treatment was common among our sample and associated with injection initiation. Findings highlight the need for easily accessible, evidence-based addiction treatment for high-risk youth as a means to prevent injection initiation and subsequent serious drug-related harms.
PMCID: PMC4702392  PMID: 26733043
Injection initiation; At-risk youth; Addiction treatment; Injection prevention
13.  The Impact of Childhood Emotional Abuse on Violence among People Who Inject Drugs 
Drug and alcohol review  2014;34(1):4-9.
Introduction and Aims
Childhood emotional abuse is a known risk factor for various poor social and health outcomes. While people who inject drugs (IDU) report high levels of violence, in addition to high rates of childhood maltreatment, the relationship between childhood emotional abuse and later life violence within this population has not been examined.
Design and Methods
Cross-sectional data were derived from an open prospective cohort of IDU in Vancouver, Canada. Childhood emotional abuse was measured using the Childhood Trauma Questionnaire. We used multivariate logistic regression to examine potential associations between childhood emotional abuse and being a recent victim or perpetrator of violence.
Between December 2005 and May 2013, 1437 IDU were eligible for inclusion in this analysis, including 465 (32.4%) women. In total, 689 (48.0%) reported moderate to severe history of childhood emotional abuse, while 333 (23.2%) reported being a recent victim of violence and 173 (12.0%) reported being a recent perpetrator of violence. In multivariate analysis, being a victim of violence (adjusted odds ratio = 1.49, 95% confidence interval 1.15–1.94) and being a perpetrator of violence (adjusted odds ratio = 1.58, 95% confidence interval 1.12–2.24) remained independently associated with childhood emotional abuse.
Discussion and Conclusions
We found high rates of childhood emotional abuse and subsequent adult violence among this sample of IDU. Emotional abuse was associated with both victimisation and perpetration of violence. These findings highlight the need for policies and programs that address both child abuse and historical emotional abuse among adult IDU.
PMCID: PMC4167988  PMID: 24635836
emotional abuse; trauma; violence; injection drug use
14.  High-intensity cannabis use and adherence to antiretroviral therapy among people who use illicit drugs in a Canadian setting 
AIDS and behavior  2015;19(1):120-127.
Cannabis is increasingly prescribed clinically and utilized by people living with HIV/AIDS (PLWHA) to address symptoms of HIV disease and to manage side effects of antiretroviral therapy (ART). In light of concerns about the possibly deleterious effect of psychoactive drug use on adherence to ART, we sought to determine the relationship between high-intensity cannabis use and adherence to ART among a community-recruited cohort of HIV-positive illicit drug users.
We used data from the ACCESS study, an ongoing prospective cohort study of HIV-seropositive illicit drug users linked to comprehensive ART dispensation records in a setting of universal no-cost HIV care. We estimated the relationship between at least daily cannabis use in the last six months, measured longitudinally, and the likelihood of optimal adherence to ART during the same period, using a multivariate linear mixed-effects model accounting for relevant socio-demographic, behavioral, clinical and structural factors.
From May 2005 to May 2012, 523 HIV-positive illicit drug users were recruited and contributed 2430 interviews. At baseline, 121 (23.1%) participants reported at least daily cannabis use. In bivariate and multivariate analyses we did not observe an association between using cannabis at least daily and optimal adherence to prescribed HAART (Adjusted Odds Ratio = 1.12, 95% Confidence Interval [95% CI]: 0.76 – 1.64, p-value = 0.555.)
High-intensity cannabis use was not associated with adherence to ART. These findings suggest cannabis may be utilized by PLWHA for medicinal and recreational purposes without compromising effective adherence to ART.
PMCID: PMC4289662  PMID: 25012624
15.  Prevalence and Correlates of Nonmedical Prescription Opioid Use Among a Cohort of Sex Workers in Vancouver, Canada 
The nonmedical use of prescription opioids (POs) is a major public health concern, causing extensive morbidity and mortality in North America. Canada has the second highest consumption rate of POs globally and data indicate nonmedical PO use (NPOU) is growing among key populations and increasingly available in street-level drug markets. Despite accumulating evidence documenting the rise of NPOU, few studies have systematically examined NPOU in Canada among key vulnerable populations, such as sex workers. This study prospectively evaluated the prevalence and correlates of NPOU within a Vancouver cohort of sex workers over three-years follow-up.
Data were drawn from an open prospective cohort, AESHA (An Evaluation of Sex Workers Health Access) in Metro Vancouver, Canada (2010-2013). Women were recruited through outreach from outdoor street locations and indoor venues. Bivariate and multivariable logistic regression using Generalized Estimating Equations (GEE) were used to examine social and structural correlates of NPOU over 36 months.
Of the 692 sex workers at baseline, close to one-fifth (n=130, 18.8%) reported NPOU (injection or non-injection) in the last six months. In multivariable GEE analyses, factors independently correlated with recent NPOU were: exchanging sex while high (AOR 3.26, 95%CI 2.29-4.64), police harassment/arrest (AOR 1.83, 95%CI 1.43-2.35), intimate partner injects drugs (AOR 1.66, 95%CI 1.11-2.49), and recent physical/sexual intimate partner violence (AOR 1.65, 95%CI 1.21-2.24).
Our results demonstrate that nearly one-fifth of sex workers in Metro Vancouver report NPOU. Factors independently statistically associated with NPOU included exchanging sex while high, police harassment/arrest, a drug injecting intimate partner and recent physical/sexual intimate partner violence. The high prevalence of NPOU use among sex workers underscores the need for further prevention and management strategies tailored to this key population. The correlates of NPOU uncovered here suggest that structural interventions may be further implemented to ameliorate this growing concern.
PMCID: PMC4277711  PMID: 25148695
Prescription opioids; Sex workers; Drug use; Substance use; Canada
16.  Are Interferon-Free Direct-Acting Antivirals for the Treatment of HCV Enough to Control the Epidemic among People Who Inject Drugs? 
PLoS ONE  2015;10(12):e0143836.
Widely access to interferon-free direct-acting antiviral regimens (IFN-free DAA) is poised to dramatically change the impact of the HCV epidemic among people who inject drugs (PWID). We evaluated the long-term effect of increasing HCV testing, treatment and engagement into harm-reduction activities, focused on active PWID, on the HCV epidemic in British Columbia (BC), Canada.
We built a compartmental model of HCV disease transmission stratified by disease progression, transmission risk, and fibrosis level. We explored the effect of: (1) Increasing treatment rates from 8 to 20, 40 and 80 per 1000 infected PWID/year; (2) Increasing treatment eligibility based on fibrosis level; (3) Maximizing the effect of testing by performing it immediately upon ending the acute phase; (4) Increasing access to harm-reduction activities to reduce the risk of re-infection; (5) Different HCV antiviral regimens on the Control Reproduction Number Rc. We assessed the impact of these interventions on incidence, prevalence and mortality from 2016 to 2030.
Of all HCV antiviral regimens, only IFN-free DAAs offered a high chance of disease elimination (i.e. Rc < 1), but it would be necessary to substantially increase the current low testing and treatment rates. Assuming a treatment rate of 80 per 1000 infected PWID per year, coupled with a high testing rate, the incidence rate, at the end of 2030, could decrease from 92.9 per 1000 susceptible PWID per year (Status Quo) to 82.8 (by treating only PWID with fibrosis level F2 and higher) or to 65.5 (by treating PWID regardless of fibrosis level). If PWID also had access to increased harm-reduction activities, the incidence rate further decreased to 53.1 per 1000 susceptible PWID per year. We also obtained significant decreases in prevalence and mortality at the end of 2030.
The combination of increased access to HCV testing, highly efficacious antiviral treatment and harm-reduction programs can substantially decrease the burden of the HCV epidemic among PWID. However, unless we increase the current levels of treatment and testing, the HCV epidemic among PWID in BC, and in other parts of the world with similar epidemiological background, will remain a substantial public health concern for many years.
PMCID: PMC4669174  PMID: 26633652
17.  The impact of methadone maintenance therapy on heptatis c incidence among illicit drug users. 
Addiction (Abingdon, England)  2014;109(12):2053-2059.
To determine the relationship between methadone maintenance therapy (MMT) and hepatitis C (HCV) seroconversion among illicit drug users.
Generalized Estimating Equation model assuming a binomial distribution and a logit link function was used to examine for a possible protective effect of MMT use on HCV incidence.
Data from three prospective cohort studies of illicit drug users in Vancouver, Canada between 1996 and 2012.
1004 HCV antibody negative illicit drug users stratified by exposure to MMT.
Baseline and semi-annual HCV antibody testing and standardised interviewer administered questionnaire soliciting self-reported data relating to drug use patterns, risk behaviours, detailed sociodemographic data and status of active participation in an MMT program.
184 HCV seroconversions were observed for an HCV incidence density of 6.32 [95% confidence interval [CI]: 5.44 – 7.31] per 100 person-years. After adjusting for potential confounders, MMT exposure was protective against HCV seroconversion (Adjusted Odds Ratio [AOR] = 0.47; 95% CI: 0.29 - 0.76). In sub-analyses, a dose-response protective effect of increasing MMT exposure on HCV incidence (AOR = 0.87; 95% CI: 0.78 – 0.97) per increasing 6-month period exposed to MMT was observed.
Participation in methadone maintenance treatment appears to be highly protective against hepatitis C incidence among illicit drug users. There appears to be a dose-response protective effect of increasing methadone exposure on hepatitis C incidence.
PMCID: PMC4229435  PMID: 25041346
hepatitis C; HCV; illicit drug use; methadone; opioid; incident infection; seroconversion
18.  Treatment as Prevention–Where Next? 
Current HIV/AIDS reports  2014;11(4):496-504.
Purpose of Review
Uptake of antiretroviral regimens with durable virologic suppression has been shown to reduce the risk of HIV transmission. Expanding ART programs at a population-level may serve as a vital strategy in the elimination of the AIDS epidemic.
Recent findings
The global expansion of ART programs has greatly improved access to life-saving therapies, and is likely to achieve the target of 15 million individuals on therapy set by UNAIDS. In addition to the incontrovertible gains in terms of life expectancy, growing evidence demonstrates that durable virologic suppression is associated with significant reductions in HIV transmission amongst heterosexual couples and men who have sex with men. Expansion in successful ART programs, best monitored by a program-level continuum of care cascade to monitor progress in diagnosis, retention in care and virologic suppression, is associated with reductions in HIV incidence at a population level.
Expanding and sustaining successful ART delivery at a global level is a key component in a comprehensive approach to combating the HIV epidemic over the next two decades.
PMCID: PMC4268430  PMID: 25384357
Antiretroviral therapy; Treatment as Prevention; Care Cascade; Millennium Development Goals
19.  Antiretroviral treatment initiation—authors’ reply 
The Lancet. Infectious diseases  2014;14(12):1176-1177.
PMCID: PMC4364602  PMID: 25455978
20.  Association of patterns of methadone use with antiretroviral therapy discontinuation: a prospective cohort study 
BMC Infectious Diseases  2015;15:537.
Methadone maintenance therapy (MMT) is a proven treatment strategy for opioid dependent patients. Although studies have demonstrated that MMT increases contact with the medical system and improves adherence to antiretroviral therapy (ART) in HIV-positive people who inject drugs (PWID), the effect of MMT discontinuation on ART discontinuation has not been well described.
We examined the impact of continuous MMT use, MMT non-use and MMT discontinuation on the time to ART discontinuation (defined as 90 days of continuous non-use following previous enrolment) in a community-recruited prospective cohort of HIV-positive PWID followed between May 1996 and May 2013 in Vancouver, Canada. Multivariate Cox proportional hazards regression was used to examine the association between MMT use patterns and time to ART discontinuation while adjusting for socio-demographic confounders.
A total of 794 HIV-positive PWID were included during the study period. In an adjusted analysis, in comparison to those who were continuously on MMT, MMT non-use (Adjusted Hazard Ratio [AHR] = 1.44, 95 % Confidence Interval [CI]: 1.19–1.73) as well as discontinuing MMT (AHR = 1.82, 95 % CI: 1.27–2.60) were both found to be independently associated with time to ART discontinuation.
This study reinforces the known benefits of MMT use on ART adherence and demonstrates how discontinuation of MMT is independently associated with an increased risk of ART cessation. These data highlight the importance of retaining PWID on MMT.
PMCID: PMC4653887  PMID: 26586238
Methadone; Opiate substitution treatment; HIV; Antiretroviral therapy; Highly active
To examine whether there were differential rates of hepatitis C virus (HCV) incidence in injecting drug-using youths who did and did not report involvement in survival sex work.
Data were derived from 2 prospective cohort studies of injecting drug users (May 1, 1996, to July 31, 2007). Analyses were restricted to HCV antibody-negative youths who completed baseline and at least 1 follow-up assessment.
Vancouver, British Columbia, Canada.
Of 3074 injecting drug users, 364 (11.8%) were youths (aged 14-24 years) with a median age of 21.3 years and a duration of injecting drug use of 3 years.
Main Exposure
Survival sex work involvement.
Main Outcome Measure
The Kaplan-Meier method and Cox proportional hazards regression were used to compare HCV incidence among youths who did and did not report survival sex work.
Baseline HCV prevalence was 51%, with youths involved in survival sex work significantly more likely to be HCV antibody positive (60% vs 44%; P = .002). In baseline HCV antibody-negative youths, the cumulative HCV incidence at 36 months was significantly higher in those involved in survival sex work (68.4% vs 38.8%; P < .001). The HCV incidence density was 36.8 (95% confidence interval [CI], 24.2-53.5) per 100 person-years in youths reporting survival sex work involvement at baseline compared with 14.1 (9.4-20.3) per 100 person-years in youths not reporting survival sex work. In multivariate Cox proportional hazards analyses, survival sex work was the strongest predictor of elevated HCV incidence (adjusted relative hazard, 2.30; 95% CI, 1.27-4.15).
This study calls attention to the critical need for evidence-based social and structural HCV prevention efforts that target youths engaged in survival sex work.
PMCID: PMC4646708  PMID: 20048243
Drug and alcohol review  2010;29(3):271-277.
Introduction and Aims
Crack cocaine use among illicit drug users is associated with a range of health and community harms. However, long-term epidemiological data documenting patterns and risk factors for crack use initiation remain limited especially among injection drug users. We investigated longitudinal patterns of crack cocaine use among polydrug users in Vancouver, Canada.
Design and Methods
We examined the rate of crack use among injection drug users enrolled in a prospective cohort study in Vancouver, Canada between 1996 and 2005. We also used a Cox proportional hazards regression analysis to identify independent predictors of crack use initiation among this population.
In total, 1603 injection drug users were recruited between May 1996 and December 2005. At baseline, 7.4% of participants reported ever using crack and this rate increased to 42.6% by the end of the study period (Mantel trend test P < 0.001).
Independent predictors of crack use initiation during the study period included frequent cocaine injection, crystal methamphetamine injection, residency in the city's drug using epicenter and involvement in the sex trade (all P < 0.05).
Discussion and Conclusions
These findings demonstrate a massive increase in crack use among injection drug users in a Canadian setting. Our findings also highlight the complex interactions that contribute to the initiation of crack use among injection drug users and suggest that evidence-based interventions are urgently needed to address crack use initiation and to address harms associated with its ongoing use.
PMCID: PMC4643832  PMID: 20565519
crack cocaine; injection drug use; initiation; Vancouver; predictive modelling
23.  Process Monitoring of an HIV Treatment as Prevention Program in British Columbia, Canada 
In light of accumulated scientific evidence of the secondary preventive benefits of antiretroviral therapy, a growing number of jurisdictions worldwide have formally started to implement HIV Treatment as Prevention (TasP) programs. To date, no gold standard for TasP program monitoring has been described. Here, we describe the design and methods applied to TasP program process monitoring in British Columbia (BC), Canada.
Monitoring indicators were selected through a collaborative and iterative process by an interdisciplinary team including representatives from all five regional health authorities, the BC Centre for Disease Control (BCCDC), and the BC Centre for Excellence in HIV/AIDS (BC-CfE). An initial set of 36 proposed indicators were considered for inclusion. These were ranked on the basis of eight criteria: data quality, validity, scientific evidence, informative power of the indicator, feasibility, confidentiality, accuracy, and administrative requirement. The consolidated list of indicators was included in the final monitoring report, which was executed using linked population-level data.
A total of 13 monitoring indicators were included in the BC TasP Monitoring Report. Where appropriate, indicators were stratified by subgroups of interest, including HIV risk group and demographic characteristics. Six Monitoring Reports are generated quarterly: one for each of the regional health authorities and a consolidated provincial report.
We have developed a comprehensive TasP process monitoring strategy using evidence-based HIV indicators derived from linked population-level data. Standardized longitudinal monitoring of TasP program initiatives is essential to optimize individual and public health outcomes and to enhance program efficiencies.
PMCID: PMC4257704  PMID: 25072608
HIV; treatment as prevention; monitoring; TasP; Canada
24.  Correlates of Unstructured Antiretroviral Treatment Interruption in a Cohort of HIV-Positive Individuals in British Columbia 
AIDS and behavior  2014;18(11):2240-2248.
Treatment interruptions (TIs) limit the therapeutic success of combination antiretroviral therapy and are associated with higher morbidity and mortality. HIV-positive individuals dealing with concurrent health issues, access challenges and competing life demands are hypothesized to be more likely to interrupt treatment. Individuals were included if they initiated cART ≥1 year prior to interview date and had a CD4 cell count or initial regimen recorded at initiation. Using pharmacy recording, TIs were defined as a patient-initiated interruption in treatment ≥90 consecutive days during the 12 months preceding or following the study interview. 117 (15%) of 768 participants included in this study had a TI during the study window. 76.0% of participants were male, 27.5% were of Aboriginal ethnicity and the median age was 46 (interquartile range (IQR): 40–52). In multivariable logistic regression, TIs were significantly associated with current illicit drug use (adjusted odds ratio [aOR]: 1.68, 95% confidence interval [CI]: 1.05–2.68); <95% adherence in the first year of treatment (aOR: 2.68, 95% CI: 1.67–4.12); living with more than one person (aOR: 1.95; 95% CI: 1.22–3.14) or living on the street (aOR: 5.08, 95% CI: 1.72–14.99) compared to living alone; poor perception of overall health (aOR: 1.64 95% CI: 1.05–2.55); being unemployed (aOR: 2.22, 95% CI: 1.16–4.23); and younger age at interview (aOR: 0.57, 95% CI: 0.44–0.75, per 10 year increment). Addressing socioeconomic barriers to treatment retention is vital for supporting the continuous engagement of patients in care.
PMCID: PMC4273743  PMID: 24781638
Treatment interruption; HIV; ART; barriers
Supervised injecting facilities (SIFs) provide a sanctioned space for injection drug users and are associated with decreased overdose mortality and HIV risk behaviors among adults. Little is known about SIF use among youth. We identified factors associated with use of the Vancouver SIF, the only such facility in North America, among street youth.
From September 2005 to May 2012, we collected data from the At-Risk Youth Study (ARYS), a prospective cohort of street youth in Vancouver, Canada. Eligible youth were aged 14–26 years. Participants reporting injection completed questionnaires at baseline and semiannually. We used generalized estimating equation logistic regression to identify factors associated with SIF use.
During the study period, 42.3% of 414 injecting youth reported use of the SIF at least once. Of all SIF-using youth, 51.4% went to the facility at least weekly, and 44.5% used it for at least one-quarter of all injections. SIF-using youth were more likely to live or spend time in the neighborhood surrounding the SIF (adjusted odds ratio [AOR], 3.29; 95% confidence interval [CI], 2.38–4.54), to inject in public (AOR, 2.08; 95% CI, 1.53–2.84), or to engage in daily injection of heroin (AOR, 2.36; 95% CI, 1.72–3.24), cocaine (AOR, 2.44; 95% CI, 1.34–4.45), or crystal methamphetamine (AOR, 1.62; 95% CI, 1.13–2.31).
This study, the first examining SIF use among street youth in North America, demonstrated that the facility attracted high-frequency young drug users most at risk of blood-borne infection and overdose, and those that otherwise inject in public spaces.
PMCID: PMC4209311  PMID: 24925493
drug abuse; adolescent; needle sharing; HIV; hepatitis C

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