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The Cedar Project: high incidence of HCV infections in a longitudinal study of young Aboriginal people… Spittal, Patricia M; Pearce, Margo E; Chavoshi, Negar; Christian, Wayne M; Moniruzzaman, Akm; Teegee, Mary; Schechter, Martin T Aug 9, 2012

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RESEARCH ARTICLE Open AccessThe Cedar Project: high incidence of HCVinfections in a longitudinal study of youngAboriginal people who use drugs in twoCanadian citiesPatricia M Spittal1,2,6*, Margo E Pearce1,2, Negar Chavoshi1,2, Wayne M Christian3, Akm Moniruzzaman4,Mary Teegee5 and Martin T Schechter1,2AbstractBackground: Factors associated with HCV incidence among young Aboriginal people in Canada are still not wellunderstood. We sought to estimate time to HCV infection and the relative hazard of risk factors associated HCVinfection among young Aboriginal people who use injection drugs in two Canadian cities.Methods: The Cedar Project is a prospective cohort study involving young Aboriginal people in Vancouver andPrince George, British Columbia, who use illicit drugs. Participants’ venous blood samples were drawn and testedfor HCV antibodies. Analysis was restricted to participants who use used injection drugs at enrolment or any offollow up visit. Cox proportional hazards regression was used to identify independent predictors of time to HCVseroconversion.Results: In total, 45 out of 148 participants seroconverted over the study period. Incidence of HCV infection was26.3 per 100 person-years (95% Confidence Interval [CI]: 16.3, 46.1) among participants who reported using injectiondrugs for two years or less, 14.4 per 100 person-years (95% CI: 7.7, 28.9) among participants who had been usinginjection drugs for between two and five years, and 5.1 per 100 person-years (95% CI: 2.6,10.9) among participantswho had been using injection drugs for over five years. Independent associations with HCV seroconversion wereinvolvement in sex work in the last six months (Adjusted Hazard Ratio (AHR): 1.59; 95% CI: 1.05, 2.42) compared tono involvement, having been using injection drugs for less than two years (AHR: 4.14; 95% CI: 1.91, 8.94) and forbetween two and five years (AHR: 2.12; 95%CI: 0.94, 4.77) compared to over five years, daily cocaine injection in thelast six months (AHR: 2.47; 95% CI: 1.51, 4.05) compared to less than daily, and sharing intravenous needles in thelast six months (AHR: 2.56; 95% CI: 1.47, 4.49) compared to not sharing.Conclusions: This study contributes to the limited body of research addressing HCV infection among Aboriginalpeople in Canada. The HCV incidence rate among Cedar Project participants who were new initiates of injectiondrug use underscores an urgent need for HCV and injection prevention and safety strategies aimed at supportingyoung people surviving injection drug use and sex work in both cities. Young people must be afforded theopportunity to provide leadership and input in the development of prevention programming.* Correspondence: spittal@sm.hivnet.ubc.ca1Centre for Health Evaluation and Outcome Sciences, Vancouver, BC, Canada2University of British Columbia, Vancouver, BC, CanadaFull list of author information is available at the end of the article© 2012 Spittal et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.Spittal et al. BMC Public Health 2012, 12:632http://www.biomedcentral.com/1471-2458/12/632BackgroundIncreasing levels of HCV infection among young Abori-ginal people are distressing for many Aboriginal com-munities and service providers, not only in small andlarge urban centres but also in rural settings wherehealthcare resources are limited [1,2]. This situation isexacerbated by the fact that the major consequences ofHCV infection, including cirrhosis of the liver and hepa-tocellular cancer do not develop for many decades afterinitial infection [3]. Available data have demonstratedthat Aboriginal people are not only disproportionatelyrepresented among HCV infected people in Canada butalso underrepresented in community based treatmentprograms [4]. In British Columbia, it is estimated thatincidence for HCV infection is twice as high amongAboriginal people compared to non-Aboriginal people[5] and that over half the population of Aboriginalpeople living with HIV are HCV co-infected, making thetreatment challenges associated with being HCV andHIV co-infected far more complex [6]. Unfortunately,national HCV surveillance data for indigenous people inCanada is considered to be very limited largely becauseof under reporting and lack of consistent documentationof ethnic status between provinces [7,8]. Despite theselimitations the Public Health Agency of Canada hasidentified that HCV incidence among Aboriginal peoplein Canada is 5 to 6 fold higher than among non-Aboriginal people [8]. The majority of these new infec-tions can be attributed to injection drug use and thesharing of contaminated injection equipment [7,9].There is also increasing evidence that HCV is dispro-portionately impacting Aboriginal young people. As Royet al [10]. have suggested, recent onset of injection is aparticularly vulnerable time for young people and therisk for HCV seroconversion is extremely high. In a pre-vious study, we demonstrated that approximately 11% ofour participants will transition to injection drug use peryear; a rate that is twice as high as that found in a simi-lar longitudinal investigation conducted in Montreal[11,12]. A number of prospective studies in Canada haveexamined HCV infection among people who use injec-tion drugs. However, most have been limited by the factthat they are older cohorts and characterized by highHCV prevalence and small numbers of Aboriginalpeople, making it difficult to assess risk factors relevantfor Aboriginal specific programming.Concerns over the paucity of available data and thepotential for explosive HIV and HCV epidemics amongAboriginal young people in other areas of the provincesimilar to those reported in the mid-1990s in Vancou-ver’s downtown eastside prompted the initiation of atwo city cohort study to address the specific HIV andHCV related vulnerabilities of Aboriginal young peoplewho use illicit drugs. To our knowledge, this is the onlylongitudinal study of young and ‘at risk’ indigenous peo-ples of its kind in North America. Follow-up of the co-hort allowed us to estimate the incidence of HCVinfection among young people enrolled in the CedarProject and identify risk factors associated with serocon-version among study participants.MethodsThe Cedar Project is an ongoing prospective study ofyoung Aboriginal people who use drugs in Vancouverand Prince George, Canada. Previous studies havedescribed the methodology of the Cedar study in detailincluding the proportion of Aboriginal young people liv-ing in BC, participant recruitment and questionnaire de-sign [13]. Briefly, young people who self identified asAboriginal people were considered to be the descendantsof the First Nation Peoples of North America and in-clude Métis, Aboriginal, First Nations, Inuit and statusand non-status Indians. Participants living primarily inthe downtown areas of both cities were recruitedthrough referral by health care providers, communityoutreach and word of mouth. Eligibility criteria forstudy entry included age 14 to 30 years and to havesmoked or injected illicit drugs, aside from marijuana,in the month prior to enrolment. Saliva screens (Oral-screen, Avitar Onsite Diagnostics) were used to con-firm drug use. All participants met with one FirstNations study coordinator who explained procedures,sought informed consent and confirmed study eligibil-ity. At enrolment, participants completed a detailedinterviewer-administered questionnaire to elicit infor-mation on socio-demographic characteristics, non-injection and injection drug use, injection practices,sexual vulnerability and service utilization. Participantswere followed-up every six months for subsequentinterviews. Venous blood samples were drawn andtested for HIV and HCV-antibodies at each visit, andeach participant had private interviews including pre-and post-test counselling with trained nurses. Partici-pants were requested but not required to return fortheir HIV/HCV serostatus test results and given atwenty dollar stipend at each study visit.Since they were established in 2010, we have enthusi-astically embraced the Tri-Council Policy Statement:Ethical Conduct for Research Involving Humans, withparticular attention to Section 9, which pertains to re-search involving Aboriginal participants. Our FirstNations collaborators and investigators were involvedin the conception, design and interpretation of thisstudy and approved this manuscript for publication.The University of British Columbia/Providence HealthCare Research Ethics Board has also approved thestudy.Spittal et al. BMC Public Health 2012, 12:632 Page 2 of 10http://www.biomedcentral.com/1471-2458/12/632Outcome variables and covariatesThe main outcome of interest in this study was HCVantibody seroconversion among participants whoreported injection drug use between January 2003 andJanuary 2009. We used algorithms for HCV serologictesting similar to those used in other studies conductedin this region [14]. In brief, AxSYM HCV version 3.0(Abbott Laboratories, Chicago, Ill.) was used to screenall plasma samples. Negative samples did not undergofurther testing. All positive samples underwent furthertesting with the recombinant Ortho HCV 3.0 ELISA testsystem (Ortho Clinical Diagnostic Inc., Rochester, NY).Samples that tested positive with both assays were classi-fied as positive. Samples that tested positive by theAxSYM HCV test and negative by the Ortho HCV testwere classified as negative. Because of the known associ-ation of the HCV virus with parenteral drug use, HCVincidence rates were estimated by three categories usingthe variable time since initiation of injection drug use.The variable was coded for relatively equal distributionbetween participants who had been injecting for <2 years(n = 40), those who had been injecting for 2–5 years(n = 40) and those who had been injecting for over5 years (n = 66).The following fixed dichotomous baseline covariateswere used in the analysis: interviewed in Vancouver; sex;identifying as gay, lesbian, bisexual or two-spirited; hav-ing at least one parent who had attended residentialschool; ever having been placed into foster care; everhaving attempted suicide; and ever having experiencedsexual abuse. Sexual abuse was defined as any type ofsexual activity into which participants had either beenforced or coerced (including childhood sexual abuse,molestation, rape and sexual assault). Nonfixed (oc-curred in the past six months) covariates included age,being in a relationship, having lived on the streets for aperiod of three nights or more, having been in jail orprison overnight or longer, having been denied shelterbecause of drug use, having been involved in sex work,having any sexually transmitted infection, having beenincarcerated overnight or longer, presence of antibodiesto HIV, time since initiation of injection drug use, dailyvs. less than daily use of injection cocaine, daily vs. lessthan daily use of injection opioids (including heroin,morphine, methadone, dilaudid or talwin and speedballs(combination of cocaine and heroin)), daily vs. less thandaily use of injection methamphetamine, rig sharing,having overdosed, and inconsistent use of condoms dur-ing insertive sex (vaginal, anal) with casual, regular orclient partners. Sexual assault was defined as havingexperienced sexual violence in the past six months. Sexwork was defined as receiving money, shelter, food ordrugs in exchange for sex. Sexual relationships thatlasted less than three months were defined as casualsexual partners, more than three months were definedas regular partners, and clients were relationships wheresex was exchanged for money, food, drugs or shelter.The Cedar Project cohort includes 605 participants intotal, however this study included only participants whoreported injection drug use, were HCV negative at base-line, reported injection drug use and who returned for atleast one of eight follow-up interviews up to December2008 (n = 148). HCV incidence was calculated as inci-dence density. HCV incidence was calculated separatelyfor groups including participants from Vancouver andPrince George, all participants together, and for partici-pants who had been using injection drugs for less thantwo years, those who had been using injection drugs forbetween two and five years, and those who had beenusing injection drugs for five or more years. The date ofseroconversion was estimated using the midpoint be-tween the last negative and the first positive antibodytest result. Cumulative incidence rates of HCV infectionwere calculated using Kaplan Meier methods. In theseanalyses time 0 was defined as the date of enrolment.We assessed the proportionality assumptions using thelog minus log curve for the fixed covariates used in themodel and observed no violations of assumptions. Parti-cipants who consistently remained HCV seronegativewere considered to be right censored at the time of theirmost recent test result. Annual rates of HCV serocon-version were calculated with actuarial methods per 100person years. Relative risks and 95% confidence intervalswere obtained for risk factors of interest.Cox proportional hazards regression were used toexamine the independent effect of both fixed and time-dependent covariates on time to HCV seroconversion.Adjusted and unadjusted time dependent Cox regressionmodels were used to identify risk associations with HCVseroconversion with Hazard Ratios and 95% confidenceintervals were obtained for risk factors of interest. Back-ward stepwise Cox proportional hazards model includedall variables that were statistically associated with HCVseroconversion at a p <0.10 significance level in un-adjusted analyses. The adjusted model controlled for thesignificant covariates to determine which of those riskfactors are independently associated with HCV serocon-version. All reported p-values are two-sided.Overall, 605 (305 in Vancouver and 300 in PrinceGeorge) young Aboriginal people were recruited andscreened for enrolment in the Cedar Project study.Among them, 292 (48%) were women and the mean agewas 23.5 years (Standard Deviation (SD): 4.0). A total of335 (55.4%) participants reported that they had used in-jection drugs before enrolment, and 42 (6.9%) reportedthat they had initiated injection drug use in the time afterenrolment. The mean age of first having injected drugswas 20.2 years (SD: 4.6). Among the 377 participantsSpittal et al. BMC Public Health 2012, 12:632 Page 3 of 10http://www.biomedcentral.com/1471-2458/12/632who had injected drugs over the study period, 175 wereHCV seronegative at time of their baseline interview.Out of 175 participants, 148 completed at least onefollow-up visit, yielding a follow-up rate of 85%. In total,148 participants were therefore eligible for inclusion inthe HCV incidence analysis.ResultsIn total, 148 participants were eligible for inclusion in theanalysis. Descriptive baseline statistics are provided inTable 1. The median age of participants at baseline was23 years (standard deviation: 3.9), 53.4% were womenand 57.4% were located in Vancouver. In addition, 11.5%identified as gay/lesbian/bisexual/transgender or two-spirited, 52.1% reported that they had ever been sexu-ally abused and 68.2% had ever been taken from theirbiological parents into the child welfare system. Intotal, these 148 participants contributed 338.6 personyears of observation over the study period. The meanlength of follow-up time was 2.6 years (SD: 1.6) for allparticipants, 1.3 years (SD: 1.1) for those who becameHCV positive and 3.2 years (SD: 1.5) for those whoremained HCV negative. Table 2 demonstrates the inci-dence of HCV among Cedar Project participants over-all, and among those who reported using injectiondrugs for 2 years or less, between 2-5 years and over 5years. Overall, 45 participants seroconverted during theobservation period yielding an incidence density of 11.6cases per 100 person years (95% Confidence Interval(CI): 8.5%, 17.1%). Incidence of HCV infection washigher in Prince George than in Vancouver (14.8 vs.9.6 per 100 person years), but this difference was notstatistically significant (Log-rank test, p = 0.186). Inci-dence of HCV infection was 26.3 per 100 person-years(95% CI: 16.3, 46.1) among participants who reportedusing injection drugs for two years or less, 14.4 per100 person-years (95% CI, 7.7, 28.9) among participantswho had been using injection drugs for between twoand five years, and 5.1 per 100 person-years (95% CI:2.6,10.9) among participants who had been in using in-jection drugs for over five years.Figure 1 demonstrates the survival estimates for timeto HCV seroconversion among participants who hadonly been injecting for two years or less, those who hadbeen using injection drugs for between two and fiveyears, and those who had been injecting for over fiveyears. For those newest to injection drug use, the cumu-lative HCV incidence increased sharply to approximately38% within the first year of follow-up and was over 50%by the third year of follow-up.Results from unadjusted and adjusted Cox regressionanalyses for factors associated with HCV incidence aredisplayed in Table 1. In unadjusted analyses, risk forHCV seroconversion was significantly associated withhaving been involved in sex work in the last six months(Unadjusted Hazard Ratio (UHR): 1.79; 95% CI: 1.16,2.53). Risk for seroconversion appeared to decline withduration of injecting, as the hazard for HCV was signifi-cantly higher for participants who reported having beeninjecting drugs for less than two years (UHR: 4.57; 95%CI: 2.91, 9.51), and for those who had been injecting forbetween two and five years (UHR: 2.43; 95% CI: 1.09,5.45) compared to those who had been injecting for fiveor more years. HCV risk also appeared to rise withincreased frequency of injection, as participants whoreported daily cocaine injection in the last six months(UHR: 3.94; 95% CI: 2.49, 6.24) and daily opioid injec-tion in the last six months (UHR: 2.06; 95% CI: 1.43,2.98) had significantly higher rates of HCV incidencecompared to participants who were injecting cocaine oropioids less than daily. In addition, participants whoreported unsafe injection practices in the last six monthsincluding sharing rigs (UHR: 3.35; 95% CI: 2.09, 5.39),reusing one’s own rig (UHR: 2.17; 95% CI: 1.48, 3.19)and having a difficult time finding new rigs (UHR: 2.16;95% CI: 1.31, 3.57) had significantly higher risk for HCVseroconversion.In the adjusted backward stepwise Cox regressionmodel, independent associations with HCV seroconver-sion among Cedar Project participants who used injec-tion drugs were involvement in sex work in the last sixmonths (Adjusted Hazard Ratio (AHR): 1.59; 95% CI:1.05, 2.42), having been using injection drugs for lessthan two years (AHR: 4.14; 95% CI: 1.91, 8.94) and forbetween two and five years (AHR: 2.12; 95%CI: 0.94-4.77), daily cocaine injection in the last six months(AHR: 2.47; 95% CI: 1.51, 4.05) and sharing rigs in thelast six months (AHR: 2.56; 95% CI: 1.47, 4.49).DiscussionOur findings have illustrated that young Aboriginalpeople are at very high risk of HCV infection early intheir injection careers. The declining risk with longerdurations of injection was not surprising. It is likely thata form of survivorship bias is operative here. The ana-lysis was based on those who were HCV negative at re-cruitment, therefore highest risk individuals in thelonger-using groups would have seroconverted to HCVprior to the study, leaving lower risk groups for inclusionin this analysis. However, it is shocking that approxi-mately 26% of participants became infected with HCVwithin two years of initiating injection drug use in twocities with established harm reduction programs. It isclear from this observation that the timeframe in whichto provide access to meaningful preventative interven-tions after these young people initiate injection drug useis very short and that harm reduction programs must doa better job of reaching them [11,15,16].Spittal et al. BMC Public Health 2012, 12:632 Page 4 of 10http://www.biomedcentral.com/1471-2458/12/632Table 1 Unadjusted and adjusted* backward stepwise Cox regression models for vulnerabilities associated with HCVincidence among Cedar participants who used injection drugs (n = 148)Variable Baseline^n (%)Unadjusted HR(95% CI)P value Adjusted HR(95% CI)P valueLocation -Prince George 63 (42.6) 1.48 (0.82, 2.66) 0.676Vancouver 85 (57.4) 1.0 (Reference)SexFemale 79 (53.4) 1.43 (0.79, 2.60) -Male 69 (46.6) 1.0 (Reference) 0.240Age at enrolment 23.1** (3.9) 0.95 (0.87, 1.02) 0.161 - -Sexual identityGay/bisexual/two-spirited 17 (11.5) 1.62 (0.72, 3.63) 0.242 - -Straight 131 (88.5) 1.0 (Reference)At least one parent in residential school - -Yes 81 (54.7) 0.95 (0.53, 1.70) 0.850No/unsure 67 (45.3) 1.0 (Reference)Ever taken into foster care - -Yes 101 (68.2) 1.29 (0.67, 2.51) 0.445No 47 (31.8) 1.0 (reference)Ever sexually abused -Yes 76 (52.1) 1.66 (0.91, 3.04) 0.098 -No/unsure 70 (47.9) 1.0 (reference)Sexual assault last 6 months - -Yes 3 (2) 1.19 (0.37, 3.85) 0.770No 145 (98) 1.0 (reference)Relationship status last 6 months - -Single 115 (77.8) 0.96 (0.64, 1.45) 0.856In a relationship 33 (22.2) 1.0 (Reference)Ever on streets for >3 nights 0.845 - -Yes 56 (38.1) 0.94 (0.52, 1.72)No 91 (61.9) 1.0 (reference)On street for > nights last 6 months -Yes n/a 1.26 (0.83, 1.90) 0.275 -No 1.0 (reference)Ever been in jail prisonYes 97 (66) 1.11 (0.59, 2.09) 0.742 - -No 50 (34) 1.0 (reference)Been in jail or prison last 6 months - -Yes 38 (25.7) 1.25 (0.83, 1.89) 0.291No 110 (74.3) 1.0 (reference)Ever attempted suicideYes 66 (44.6) 0.67 (0.37, 1.23) 0.195 - -No 82 (55.4) 1.0 (reference)Number of lifetime sexual partners 0.530 - ->20 70 (48.6) 1.21 (0.67, 2.18)<20/refused 74 (51.4) 1.0 (reference)Spittal et al. BMC Public Health 2012, 12:632 Page 5 of 10http://www.biomedcentral.com/1471-2458/12/632Table 1 Unadjusted and adjusted* backward stepwise Cox regression models for vulnerabilities associated with HCVincidence among Cedar participants who used injection drugs (n = 148) (Continued)Ever involved in sex work - -Yes 67 (45.6) 1.63 (0.90, 2.96) 0.107No 80 (54.4) 1.0 (reference)Involved in sex work last 6 monthsYes 47 (31.8) 1.71 (1.16, 2.53) 0.007 1.59 (1.05, 2.42) 0.030No 101 (68.2) 1.0 (reference) 1.0 (reference)Condom use for insertive sex with regular partner last 6 months - -Not always 62 (41.9) 0.82 (0.51, 1.34) 0.437Always 86 (58.1) 1.0 (reference)Condom use for insertive sex with causal partner last 6 months - -Not always 28 (18.9) 0.60 (0.24, 1.48) 0.268Always 120 (81.1) 1.0 (reference)Condom use for insertive sex with clients last 6 months - -Not always 6 (4.1) 1.96 (0.61, 6.36) 0.260Always 142 (95.9) 1.0 (reference)Ever had a STIYes 65 (43.9) 1.17 (0.65, 2.12) - -No 83 (56.1) 1.0 (reference) 0.604Had a STI last 6 monthsYes 16 (10.8) 0.94 (0.36, 2.50) 0.908 - -No 132 (89.2) 1.0 (reference)Ever overdoseYes 48 (32.4) 0.76 (0.42, 1.40) 0.382 - -No 100 (67.6) 1.0 (reference)Overdose last 6 monthsYes 20 (13.5) 1.71 (0.82, 3.58) 0.152 - -No 128 (86.5) 1.0 (reference)Time since initiation of injection drug use1< 2 years n/a 4.57 (2.19, 9.51) <0.001 4.14 (1.91, 8.94) <0.0012-5 years 2.43 (1.09, 5.45) 0.031 2.12 (0.94, 4.77) 0.070> 5 years 1.0 (reference) 1.0 (reference)Frequency of injection cocaine last 6 monthsDaily 16 (10.8) 3.94 (2.49, 6.24) <0.001 2.47 (1.51, 4.05) <0.001< Daily/non-user 132 (89.2) 1.0 (reference) 1.0 (reference)Frequency of injection methamphetamine last 6 months - -Daily 4 (2.7) 1.79 (0.90, 3.57) 0.099< Daily/non-user 144 (97.3) 1.0 (reference)Frequency of injection opiates last 6 months - -Daily 27 (18.2) 2.06 (1.43, 2.98) <0.001< Daily/non-user 125 (81.7) 1.0 (reference)Syringe sharing last 6 monthsYes 19 (12.8) 3.35 (2.09, 5.39) <0.001 2.56 (1.47, 4.49) 0.001No 129 (87.2) 1.0 (reference) 1.0 (reference)Spittal et al. BMC Public Health 2012, 12:632 Page 6 of 10http://www.biomedcentral.com/1471-2458/12/632This study also demonstrated that participants whoreported frequent drug injection and syringe sharingover the study period had over twice the risk for HCVinfection. Poly-drug use was common in this group.More than half of those who reported daily cocaine in-jection also reported daily opiate injection (data notshown). It is noteworthy that daily cocaine injectionremained associated with HCV infection in the multi-variable model while daily opiate injection did not. Thisis consistent with a previous study in Vancouver thatdemonstrated acquisition of HIV among injection drugusers was directly related to frequent use of injectioncocaine as opposed to opiates, particularly as a conse-quence of ‘cocaine binges’ [17]. We find it very concern-ing that despite scaling up harm reduction efforts, highintensity injection cocaine and syringe sharing continuesto be exposing Cedar Project participants to high riskfor HCV infection in both the northern and southernurban communities. Increased efforts must be made toengage young people who are new to injection drug usein harm reduction service provision, including injectionequipment, addiction treatment and HIV and HCV test-ing services. Moreover, while early intervention withyoung people who have recently transitioned to injectionTable 1 Unadjusted and adjusted* backward stepwise Cox regression models for vulnerabilities associated with HCVincidence among Cedar participants who used injection drugs (n = 148) (Continued)Reuse of own syringes last 6 months - -Yes 13 (9.1) 2.17 (1.48, 3.19) <0.001No 131 (90.9) 1.0 (reference)Hard to find new syringes last 6 months - -Yes 15 (10.1) 2.16 (1.31, 3.57) 0.003No 133 (89.9) 1.0 (reference)Need help injecting last 6 months - -Yes 38 (25.7) 1.14 (0.61, 2.14) 0.687No 110 (74.3) 1.0 (reference)Accessed any alcohol or drug treatment program last 6 months - -Yes 31 (21.1) 1.25 (0.81, 1.93) 0.317No 116 (78.9) 1.0 (reference)Unable to access drug treatment program - -Yes 22 (15) 0.90 (0.48, 1.69) 0.741No 125 (85) 1.0 (reference)Currently in methadone treatment program - -Yes 5 (3.4) 2.11 (0.83, 5.37) 0.117No 143 (96.6) 1.0 (reference)*All variables significant at the p≤ 0.10 level in unadjusted analysis were included in the adjusted backward stepwise Cox proportional hazards model.HR Hazard Ratio.^Responses with less than n = 148 participants reflect missing data.**Mean age (standard deviation).1For those who had seroconverted to HCV positive, variable was time to seroconversion; and those who were non-incident cases, variable measured time to lastfollow up visit since initiation of injection.n/a: not available.Table 2 HCV incidence among Cedar Project participants who had been using injection drugs for less than 2 years,2–5 years and over 5 yearsHCV incidence Incident cases Total personyearsIncidence density(per 100 person years)95% Confidence Interval(per 100 person years)Overall 45 387.9 11.6 8.5- 17.1≤2 years since initiation of injection drug use 21 79.7 26.3 16.3-46.12-5 years since initiation of IDU 13 90.4 14.4 7.7-28.9Over 5 years since initiation of IDU 11 214.5 5.1 2.6-10.9Spittal et al. BMC Public Health 2012, 12:632 Page 7 of 10http://www.biomedcentral.com/1471-2458/12/632drug use is immediately required, programming aimedat prevention of injection drug use must also be priori-tized. In both Vancouver and Prince George, the com-plex interplay between the impact of colonization,residential schools, racialized care, and generations ofmistrust of both provincial and federal authorities mustbe acknowledged [18]. When designing new program-ming service providers must be mindful of how the pastcan shape the response to prevention initiatives [19] andnurture flexible, trust-based relationships that seek tobuild upon young Aboriginal people’s resiliency in theface of intergenerational and lifetime traumas [20]. Anyefforts to alleviate the immense impact of drug relatedharm but be inclusive of the perspectives of those youngpeople who have learned how to ‘remain safe’ and haveavoided infection via injection drug use [21]. Further-more, young people must be afforded the opportunity toprovide leadership in programme design intended to re-flect their needs.An independent association was also found in thisstudy between recent involvement in sex work and HCVseroconversion. These results provide evidence that therisk for HCV among participants who had been involvedin sex work was 59% higher compared to those who hadnot been involved in sex work. Recent studies conductedin British Columbia’s lower mainland have demonstratedthat impoverished Aboriginal women involved in sexwork and concomitant illicit drug use continue to beexposed to alarming levels of drug related harm, infec-tious disease and violent predation [22-24]. Sadly, thesefindings are consistent with other settings internationallywhere women exchanging sex for basic needs includingdrug dependence, are exposed to alarming levels of vio-lence and infectious disease [25]. These data indicate thecritical need for scaling up services aimed at reducingdrug or sex related harm for young Aboriginal women,particularly in Northern and remote communities. It isimportant to highlight that many young Aboriginalwomen involved in sex work are intimately involvedwith men who are usually older and who also use injec-tion drugs [23,26]. Indeed research has demonstratedthat for women who rely on their intimate partners fordrug acquisition, preparation and injection, the distribu-tion of power and control in intimate relationships oftenlies with drug injecting men who control the money andthe drugs [27,28]. Combined, these factors lead to agreater likelihood of unsafe sex and the female partnermore likely coming “second on the needle.”Several limitations of this study should be acknowl-edged. This study is based on self-reported behaviouraldata obtained from a non-probability sample of street-involved individuals. Consequently, there is potential forrecall bias, socially desirable reporting, and misclassifica-tion of exposure variables in this study. Responses to ques-tions concerning drug use and sexual behaviors may beinfluenced by the participant’s knowledge of their HCVantibody status. In addition, recall problems may existwith reporting of past traumatic life events. The effect ofmemory on our estimates of risk for these factors is diffi-cult to assess. Additionally, although data were analyzedusing time-dependent variables, we cannot make conclu-sions regarding temporal sequences between HCV riskFigure 1 Kaplan Meier Curves of HCV incidence rates by length of time participants reported use of injection drugs (2 years or less,2–5 years, and over 5 years).Spittal et al. BMC Public Health 2012, 12:632 Page 8 of 10http://www.biomedcentral.com/1471-2458/12/632patterns and infection. The number of participants whohad never used injection drugs and seroconverted to HCVpositive over the study period was very low (n= 5) we weretherefore unable to examine the risks for HCV incidenceamong those participants. Finally, the fact that HCV inci-dence was lower among participants who had been inject-ing drugs longer may be demonstrating a survivorshipbias. Therefore, perhaps the most at-risk participants whohad been injecting longest became HCV positive prior toentering the study. Nevertheless, this study does showalarming rates of HCV infection early in the injection car-eer of young Aboriginal people in Vancouver and PrinceGeorge. Despite these limitations, we believe these dataprovide important epidemiological information about ahigh-risk Aboriginal population that has not been previ-ously studied.ConclusionsResults presented in this study suggest that even in thepresence of established harm reduction initiatives inboth Vancouver and Prince George, including fixed andmobile needle distribution sites, young Aboriginalpeople who use drugs are at sustained risk for HCV in-fection. In addition, the new initiates to injection druguse were at highest risk, particularly those young peoplewho were frequently injecting cocaine, sharing rigs andinvolved in sex work. In the absence of post-exposureprophylaxis or an effective HCV vaccine, primary pre-vention programs must focus on safe injection practicesand reducing the number of people who initiate injec-tion drug use. Indeed, such high incident rates amongnew initiates in this study underscore the importance ofcarefully examining the effectiveness of current harm re-duction initiatives in both rural and urban settings. OnSeptember 30, 2011, the Supreme Court of Canada madea unanimous decision ordering the federal governmentto refrain from its attempts to close Vancouver’s super-vised injection clinic [29]. It has been speculated thatthis landmark decision will provide other Canadian citieswith the authority to open their own safe injectionclinics [30]. Although not statistically significant, thepresent study indicated a higher incidence of HCV inthe northern city of Prince George than Vancouver.Based on the estimates we have obtained in this study,we speculate similar rates of HCV infection will beobserved in smaller, northern communities throughoutBritish Columbia. In previous studies, we identified Van-couver’s safe injection facility as an integral source forharm reduction programming among Cedar Project par-ticipants who were already fully entrenched in injectiondrug use and HCV positive [31]. Taken together, thesefindings underscore the urgent need for expansion ofsafe drug use facilities to other locations in BC, includ-ing the North. Furthermore, current policies andpractices guiding addiction treatment delivery may bereinforcing the marginalization of street-involved youngAboriginal people because they fail to address historicaland social injustices that influence resilience, particularlyracial discrimination [32-34]. Treatment delivery for op-timal adherence among young, HCV positive Aboriginalpeople who inject drugs must be individually tailored,enriched with ancillary psychosocial supports and pro-vided within a culturally safe setting [7,35]. These find-ings may be applicable to at-risk young Indigenouspeople globally, for example in Australia, where similarpatterns of vulnerabilities have been identified [36]. Withsignificant increases in resources, acknowledging theintergenerational trauma related to the residential schoolsystem may be one way that Aboriginal leadership andaddiction specialists and other practitioners can begin tomitigate the potential impact of the epidemic currentlythreatening their communities.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsPMS wrote the initial draft of the manuscript was responsible forinterpretation of the findings. MEP revised subsequent drafts of themanuscript and contributed to the statistical interpretation of the findings.AKM conducted the statistical analyses and helped draft the manuscript. NC,MT, WMC and MTS were responsible for the interpretation of the findingsand revisions to the manuscript. All authors read and approved the finalversion of this manuscript.FundingThe study was supported by a grant from the Institute for Aboriginal PeoplesHealth, of the Canadian Institutes for Health Research (CIHR), which has norole in the preparation of data or manuscripts. PMS is the recipient of theCIHR New Investigator Career Award. MEP and NC are supported by CIHRdoctoral research awards. WMC is the spokesperson for the Shuswap NationTribal Council. MTS is the Chief Scientific Officer for the Michael SmithFoundation for Health Research.AcknowledgementsWe are indebted to the study participants for their continued participation inthe Cedar Project. Special thanks to the Cedar Project Partnership; the PrinceGeorge Native Friendship Centre, Carrier Sekani Family Services, Healing OurSpirit, Positive Living North, The Red Road Aboriginal HIV/AIDS Network,Central Interior Native Health, Vancouver Native Health Society, SplatsinSecwepemc Nation, Neskonlith Indian Band, and Adams Lake Indian Bandfor their conviction and for holding us accountable to the voices ofAboriginal young people. Our study staff, Vicki Thomas, Sharon Springer,Amanda Wood, Randy Dodginghorse, Janene Erickson, Matt Quenneville,and Nancy Laliberte must be thanked for their continued conviction andcontributions.Author details1Centre for Health Evaluation and Outcome Sciences, Vancouver, BC, Canada.2University of British Columbia, Vancouver, BC, Canada. 3Splatsin SecwepemcNation, Enderby, BC, Canada. 4Simon Fraser University, Vancouver, BC,Canada. 5Carrier Sekani Family Services, Prince George, BC, Canada. 6St Paul’sHospital, 620B −1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada.Received: 16 November 2011 Accepted: 25 July 2012Published: 9 August 2012References1. Hansen D: Hep C cases linked to residential schools. Vancouver: VancouverSun; 2010. B2-B2.Spittal et al. BMC Public Health 2012, 12:632 Page 9 of 10http://www.biomedcentral.com/1471-2458/12/6322. Ko HH, et al: Liver disease in the indigenous populations of the Arctic,sub-Arctic, and Pacific Northwest. BC Med J 2006, 48:216–221.3. 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Moniruzzaman A, Patel SH, Miller C, Bingham B, Spittal PM: The CedarProject: Factors associated with using Vancouver’s Safe Injection Site amongyoung Aboriginal people who use injection drugs. Toronto: Canadian PublicHealth Association Annual Conference; 2010. Oral presentation.32. Browne AJ: Clinical Encounters Between Nurses and First NationsWomen in A Western Canadian Hospital. Soc Sci Med 2007, 64:2167–2176.33. Dell CA, Lyons T: Harm Reduction Policies and Programs for Persons ofAboriginal Descent. Ottawa, Ontario: Canadian Centre on SubstanceAbuse; 2007.34. Harris R, et al: Effects of self-reported racial discrimination anddeprivation on Māori health and inequalities in New Zealand:cross-sectional study. Lancet 2006, 367:2005–2009.doi:10.1016/s0140-6736(06)68890-9.35. Smye V, Browne AJ: 'Cultural safety' and the analysis of health policyaffecting aboriginal people. Nurs Res 2002, 9:42–56.36. Iverson J, Wand H, Gonnermann A, Maher L: Gender differences inhepatitis C antibody prevalence and risk behaviours amongst peoplewho inject drugs in Australia 1998–2008. Int J Drug Policy 2010,21:471–476.doi:10.1186/1471-2458-12-632Cite this article as: Spittal et al.: The Cedar Project: high incidence ofHCV infections in a longitudinal study of young Aboriginal people whouse drugs in two Canadian cities. BMC Public Health 2012 12:632.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitSpittal et al. BMC Public Health 2012, 12:632 Page 10 of 10http://www.biomedcentral.com/1471-2458/12/632

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