The Cedar Project is an ongoing prospective study of young Aboriginal people who use drugs in Vancouver and Prince George, Canada. Previous studies have described the methodology of the Cedar study in detail including the proportion of Aboriginal young people living in BC, participant recruitment and questionnaire design . Briefly, young people who self identified as Aboriginal people were considered to be the descendants of the First Nation Peoples of North America and include Métis, Aboriginal, First Nations, Inuit and status and non-status Indians. Participants living primarily in the downtown areas of both cities were recruited through referral by health care providers, community outreach and word of mouth. Eligibility criteria for study entry included age 14 to 30 years and to have smoked or injected illicit drugs, aside from marijuana, in the month prior to enrolment. Saliva screens (Oral-screen, Avitar Onsite Diagnostics) were used to confirm drug use. All participants met with one First Nations study coordinator who explained procedures, sought informed consent and confirmed study eligibility. At enrolment, participants completed a detailed interviewer-administered questionnaire to elicit information on socio-demographic characteristics, non-injection and injection drug use, injection practices, sexual vulnerability and service utilization. Participants were followed-up every six months for subsequent interviews. Venous blood samples were drawn and tested for HIV and HCV-antibodies at each visit, and each participant had private interviews including pre- and post-test counselling with trained nurses. Participants were requested but not required to return for their HIV/HCV serostatus test results and given a twenty dollar stipend at each study visit.
Since they were established in 2010, we have enthusiastically embraced the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, with particular attention to Section 9, which pertains to research involving Aboriginal participants. Our First Nations collaborators and investigators were involved in the conception, design and interpretation of this study and approved this manuscript for publication. The University of British Columbia/Providence Health Care Research Ethics Board has also approved the study.
Outcome variables and covariates
The main outcome of interest in this study was HCV antibody seroconversion among participants who reported injection drug use between January 2003 and January 2009. We used algorithms for HCV serologic testing similar to those used in other studies conducted in this region . In brief, AxSYM HCV version 3.0 (Abbott Laboratories, Chicago, Ill.) was used to screen all plasma samples. Negative samples did not undergo further testing. All positive samples underwent further testing with the recombinant Ortho HCV 3.0 ELISA test system (Ortho Clinical Diagnostic Inc., Rochester, NY). Samples that tested positive with both assays were classified as positive. Samples that tested positive by the AxSYM HCV test and negative by the Ortho HCV test were classified as negative. Because of the known association of the HCV virus with parenteral drug use, HCV incidence rates were estimated by three categories using the variable time since initiation of injection drug use. The variable was coded for relatively equal distribution between 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 over 5 years (n = 66).
The following fixed dichotomous baseline covariates were used in the analysis: interviewed in Vancouver; sex; identifying as gay, lesbian, bisexual or two-spirited; having at least one parent who had attended residential school; ever having been placed into foster care; ever having attempted suicide; and ever having experienced sexual abuse. Sexual abuse was defined as any type of sexual activity into which participants had either been forced or coerced (including childhood sexual abuse, molestation, rape and sexual assault). Nonfixed (occurred in the past six months) covariates included age, being in a relationship, having lived on the streets for a period of three nights or more, having been in jail or prison overnight or longer, having been denied shelter because of drug use, having been involved in sex work, having any sexually transmitted infection, having been incarcerated overnight or longer, presence of antibodies to HIV, time since initiation of injection drug use, daily vs. less than daily use of injection cocaine, daily vs. less than daily use of injection opioids (including heroin, morphine, methadone, dilaudid or talwin and speedballs (combination of cocaine and heroin)), daily vs. less than daily use of injection methamphetamine, rig sharing, having overdosed, and inconsistent use of condoms during insertive sex (vaginal, anal) with casual, regular or client partners. Sexual assault was defined as having experienced sexual violence in the past six months. Sex work was defined as receiving money, shelter, food or drugs in exchange for sex. Sexual relationships that lasted less than three months were defined as casual sexual partners, more than three months were defined as regular partners, and clients were relationships where sex was exchanged for money, food, drugs or shelter.
The Cedar Project cohort includes 605 participants in total, however this study included only participants who reported injection drug use, were HCV negative at baseline, reported injection drug use and who returned for at least one of eight follow-up interviews up to December 2008 (n = 148). HCV incidence was calculated as incidence density. HCV incidence was calculated separately for groups including participants from Vancouver and Prince George, all participants together, and for participants who had been using injection drugs for less than two years, those who had been using injection drugs for between two and five years, and those who had been using injection drugs for five or more years. The date of seroconversion was estimated using the midpoint between the last negative and the first positive antibody test result. Cumulative incidence rates of HCV infection were calculated using Kaplan Meier methods. In these analyses time 0 was defined as the date of enrolment. We assessed the proportionality assumptions using the log minus log curve for the fixed covariates used in the model and observed no violations of assumptions. Participants who consistently remained HCV seronegative were considered to be right censored at the time of their most recent test result. Annual rates of HCV seroconversion were calculated with actuarial methods per 100 person years. Relative risks and 95% confidence intervals were obtained for risk factors of interest.
Cox proportional hazards regression were used to examine the independent effect of both fixed and time-dependent covariates on time to HCV seroconversion. Adjusted and unadjusted time dependent Cox regression models were used to identify risk associations with HCV seroconversion with Hazard Ratios and 95% confidence intervals were obtained for risk factors of interest. Backward stepwise Cox proportional hazards model included all variables that were statistically associated with HCV seroconversion at a p <0.10 significance level in unadjusted analyses. The adjusted model controlled for the significant covariates to determine which of those risk factors are independently associated with HCV seroconversion. All reported p-values are two-sided.
Overall, 605 (305 in Vancouver and 300 in Prince George) young Aboriginal people were recruited and screened for enrolment in the Cedar Project study. Among them, 292 (48%) were women and the mean age was 23.5 years (Standard Deviation (SD): 4.0). A total of 335 (55.4%) participants reported that they had used injection drugs before enrolment, and 42 (6.9%) reported that they had initiated injection drug use in the time after enrolment. The mean age of first having injected drugs was 20.2 years (SD: 4.6). Among the 377 participants who had injected drugs over the study period, 175 were HCV seronegative at time of their baseline interview. Out of 175 participants, 148 completed at least one follow-up visit, yielding a follow-up rate of 85%. In total, 148 participants were therefore eligible for inclusion in the HCV incidence analysis.