The Impact of Current Opioid Agonist Therapy on Hepatitis C Virus Treatment Initiation Among People Who Use Drugs From the Direct-acting Antiviral (DAA) Era: A Population-Based Study.

BACKGROUND: Evidence that opioid agonist therapy (OAT) is associated with increased odds of hepatitis C virus (HCV) treatment initiation among people who use drugs (PWUD) is emerging. The objective of this study was to determine the association between current OAT and HCV treatment initiation among PWUD in a population-level linked administrative dataset. METHODS: The British Columbia Hepatitis Testers Cohort was used for this study, which includes all people tested for or diagnosed with HCV in British Columbia, linked to medical visits, hospitalizations, laboratory, prescription drug, and mortality data from 1992 until 2019. PWUD with injecting drug use or opioid use disorder and chronic HCV infection were identified for inclusion in this study. HCV treatment initiation was the main outcome, and subdistribution proportional hazards modeling was used to assess the relationship with current OAT. RESULTS: In total, 13 803 PWUD with chronic HCV were included in this study. Among those currently on OAT at the end of the study period, 47% (2704/5770) had started HCV treatment, whereas 22% (1778/8033) of those not currently on OAT had started HCV treatment. Among PWUD with chronic HCV infection, current OAT was associated with higher likelihood of HCV treatment initiation in time to event analysis (adjusted hazard ratio 1.84 [95% confidence interval {CI}, 1.50, 2.26]). CONCLUSIONS: Current OAT was associated with a higher likelihood of HCV treatment initiation. However, many PWUD with HCV currently receiving OAT have yet to receive HCV treatment. Enhanced integration between substance use care and HCV treatment is needed to improve the overall health of PWUD.

Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study.

BACKGROUND & AIMS: We evaluated the effect of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia, Canada. METHODS: We used data from the British Columbia Hepatitis Testers Cohort, which includes people tested for HCV since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modelling to assess the effect of DAAs on mortality. RESULTS: Our cohort comprised 10,851 people treated with DAAs (SVR 10,426 [96%], no-SVR: 425) and 10,851 matched untreated individuals. Median follow-up time was 2.2 years (IQR 1.3-3.6; maximum 6.2). The all-cause mortality rate was 19.5/1,000 person-years (PY) among the SVR group (deaths = 552), 86.5/1,000 PY among the no-SVR group (deaths = 96), and 99.2/1,000 PY among the untreated group (deaths = 2,133). In the multivariable model, SVR was associated with significant reduction in all-cause (adjusted hazard ratio [aHR] 0.19; 95% CI 0.17-0.21), liver- (adjusted subdistribution HR [asHR] 0.22, 95% CI 0.18-0.27) and drug-related mortality (asHR 0.26, 95% CI 0.21-0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use (IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality. CONCLUSIONS: DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people who inject drugs. LAY SUMMARY: We assessed the effect of treatment of hepatitis C virus infection with direct-acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct-acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection.

HCV reinfection rates after cure or spontaneous clearance among HIV-infected and uninfected men who have sex with men.

BACKGROUND & AIMS: Hepatitis C virus (HCV) reinfection among high-risk groups threatens HCV elimination goals. We assessed HCV reinfection rates among men who have sex with men (MSM) in British Columbia (BC), Canada. METHODS: We used data from the BC Hepatitis Testers Cohort, which includes nearly 1.7 million individuals tested for HCV or HIV in BC. MSM who had either achieved sustained virologic response (SVR) after successful HCV treatment, or spontaneous clearance (SC) and had ≥1 subsequent HCV RNA measurement, were followed from the date of SVR or SC until the earliest of reinfection, death, or last HCV RNA measurement. Predictors of reinfection were identified by Cox proportional modelling. The earliest study start date was 6 November 1997 and latest end date was 13 April 2018. RESULTS: Of 1349 HCV-positive MSM who met the inclusion criteria, 493 had SC while 856 achieved SVR. 349 (25.65%) had HIV coinfection. We identified 98 reinfections during 5203 person-years (PYs) yielding a reinfection rate of 1.88/100PYs. The reinfection rate among SC (2.74/100PYs) was more than twice that of those with SVR (1.03/100 PYs). Problematic alcohol use (aHR 1.73, 95% CI 1.003-2.92), injection drug use (aHR 2.60, 95% CI 1.57-4.29) and HIV coinfection (aHR 2.04, 95% CI 1.29-3.23) were associated with increased risk of HCV reinfection. Mental health counselling history (aHR 0.24, 95% CI 0.13-0.46) was associated with reduced HCV reinfection risk. CONCLUSIONS: There is the need to engage MSM in harm reduction and prevention services following treatment to reduce reinfection risk.

Women in the 2019 hepatitis C cascade of care: findings from the British Columbia Hepatitis Testers cohort study.

BACKGROUND: Women living with hepatitis C virus (HCV) are rarely addressed in research and may be overrepresented within key populations requiring additional support to access HCV care and treatment. We constructed the HCV care cascade among people diagnosed with HCV in British Columbia, Canada, as of 2019 to compare progress in care and treatment and to assess sex/gender gaps in HCV treatment access. METHODS: The BC Hepatitis Testers Cohort includes 1.7 million people who tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 2000 to 2019. Test results were linked to medical visits, hospitalizations, cancers, prescription drugs, and mortality data. Six HCV care cascade stages were identified: (1) antibody diagnosed; (2) RNA tested; (3) RNA positive; (4) genotyped; (5) initiated treatment; and (6) achieved sustained virologic response (SVR). HCV care cascade results were assessed for women, and an 'inverse' cascade was created to assess gaps, including not being RNA tested, genotyped, or treatment initiated, stratified by sex. RESULTS: In 2019, 52,638 people with known sex were anti-HCV positive in BC; 37% (19,522) were women. Confirmatory RNA tests were received by 86% (16,797/19,522) of anti-HCV positive women and 83% (27,353/33,116) of men. Among people who had been genotyped, 68% (6756/10,008) of women and 67% (12,640/18,828) of men initiated treatment, with 94% (5023/5364) of women and 92% (9147/9897) of men achieving SVR. Among the 3252 women and 6188 men not yet treated, higher proportions of women compared to men were born after 1975 (30% vs. 21%), had a mental health diagnosis (42% vs. 34%) and had used injection drugs (50% vs. 45%). Among 1619 women and 2780 men who had used injection drugs and were not yet treated, higher proportions of women than men used stimulants (64% vs. 57%), and opiates (67% vs. 60%). CONCLUSIONS: Women and men appear to be equally engaged into the HCV care cascade; however, women with concurrent social and health conditions are being left behind. Treatment access may be improved with approaches that meet the needs of younger women, those with mental health diagnoses, and women who use drugs.

The "Sticky Notes" Method: Adapting Interpretive Description Methodology for Team-Based Qualitative Analysis in Community-Based Participatory Research.

Community-based participatory research (CBPR) has a long history within HIV research, yet little work has focused on facilitating team-based data analysis within CBPR. Our team adapted Thorne's interpretive description (ID) for CBPR analysis, using a color-coded "sticky notes" system to conduct data fragmentation and synthesis. Sticky notes were used to record, visualize, and communicate emerging insights over the course of 11 in-person participatory sessions. Data fragmentation strategies were employed in an iterative four-step process that was reached by consensus. During synthesis, the team created and recreated mind maps of the 969 sticky notes, from which we developed categories and themes through discussion. Flexibility, trust, and discussion were key components that facilitated the evolution of the final process. An interactive, team-based approach was central to data co-creation and capacity building, whereas the "sticky notes" system provided a framework for identifying and sorting data.

Loss to follow-up: A significant barrier in the treatment cascade with direct-acting therapies.

Effectiveness of direct-acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow-ups. Here, we evaluate loss to follow-up and treatment effectiveness of sofosbuvir/ledipasvir ± ribavirin (SOF/LDV ± RBV), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir + ribavirin (SOF + RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV-positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow-up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV ± RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r + DSV-treated patients. Overall, 453 (10.1%) individuals were lost to follow-up. Higher loss to follow-up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow-up rate was significantly higher among individuals aged <60 years, those with a history of injection drug use (IDU), on opioid substitution therapy and with cirrhosis. Our findings indicate that loss to follow-up exceeds viral failure in HCV DAA therapy and its rate varies significantly by genotype and treatment regimen. Depending on the aetiology of lost to follow-up, personalized case management for those with medical complications and supporting services among IDU are needed to achieve the full benefits of effective treatments.

Experiences of the HIV Cascade of Care Among Indigenous Peoples: A Systematic Review.

Indigenous leaders remain concerned that systemic oppression and culturally unsafe care impede Indigenous peoples living with HIV from accessing health services that make up the HIV cascade of care. We conducted a systematic review to assess the evidence related to experiences of the HIV care cascade among Indigenous peoples in Australia, Canada, New Zealand, and United States. We identified 93 qualitative and quantitative articles published between 1996 and 2017 reporting primary data on cascade outcomes disaggregated by Indigenous identity. Twelve involved data from Australia, 52 from Canada, 3 from New Zealand and 26 from United States. The majority dealt with HIV testing/diagnosis (50). Relatively few addressed post-diagnosis experiences: linkage (14); retention (20); treatment initiation (21); adherence (23); and viral suppression (24). With the HIV cascade of care increasingly the focus of global, national, and local HIV agendas, it is critical that culturally-safe care for Indigenous peoples is available at all stages.

The Cedar Project: mortality among young Indigenous people who use drugs in British Columbia.

BACKGROUND: Young Indigenous people, particularly those involved in the child welfare system, those entrenched in substance use and those living with HIV or hepatitis C, are dying prematurely. We report mortality rates among young Indigenous people who use drugs in British Columbia and explore predictors of mortality over time. METHODS: We analyzed data collected every 6 months between 2003 and 2014 by the Cedar Project, a prospective cohort study involving young Indigenous people who use illicit drugs in Vancouver and Prince George, BC. We calculated age-standardized mortality ratios using Indigenous and Canadian reference populations. We identified predictors of mortality using time-dependent Cox proportional hazard regression. RESULTS: Among 610 participants, 40 died between 2003 and 2014, yielding a mortality rate of 670 per 100 000 person-years. Young Indigenous people who used drugs were 12.9 (95% confidence interval [CI] 9.2-17.5) times more likely to die than all Canadians the same age and were 7.8 (95% CI 5.6-10.6) times more likely to die than Indigenous people with Status in BC. Young women and those using drugs by injection were most affected. The leading causes of death were overdose (n = 15 [38%]), illness (n = 11 [28%]) and suicide (n = 5 [12%]). Predictors of mortality included having hepatitis C at baseline (adjusted hazard ratio [HR] 2.76, 95% CI 1.47-5.16), previous attempted suicide (adjusted HR 1.88, 95% CI 1.01-3.50) and recent overdose (adjusted HR 2.85, 95% CI 1.00-8.09). INTERPRETATION: Young Indigenous people using drugs in BC are dying at an alarming rate, particularly young women and those using injection drugs. These deaths likely reflect complex intersections of historical and present-day injustices, substance use and barriers to care.

The Alcohol Use Disorders Identification Test (AUDIT): Exploring the Factor Structure and Cutoff Thresholds in a Representative Post-Conflict Population in Northern Uganda.

AIMS: Despite increased use of the Alcohol Use Disorders Identification Test (AUDIT) in sub-Saharan Africa, few studies have assessed its underlying conceptual framework, and none have done so in post-conflict settings. Further, significant inconsistencies exist between definitions used for problematic consumption. Such is the case in Uganda, facing one of the highest per-capita alcohol consumption levels regionally, which is thought to be hindering rebuilding in the North after two decades of civil war. This study explores the impact of varying designation cutoff thresholds in the AUDIT as well as its conceptual factor structure in a representative sample of the population. METHODS: In all, 1720 Cango Lyec Project participants completed socio-economic and mental health questionnaires, provided blood samples and took the AUDIT. Participant characteristics and consumption designations were compared at AUDIT summary score thresholds of ≥3, ≥5 and ≥8. Confirmatory factor analyses (CFA) explored one-, two- and three-factor level models overall and by sex with relative and absolute fit indicators. RESULTS: There were no significant differences in participant demographic characteristics between thresholds. At higher cutoffs, the test increased in specificity to identify those with hazardous drinking, disordered drinking and suffering from alcohol-related harms. All conceptual models indicated good fit, with three-factor models superior overall and within both sexes. CONCLUSION: In Northern Uganda, a three-factor AUDIT model best explores alcohol use in the population and is appropriate for use in both sexes. Lower cutoff thresholds are recommended to identify those with potentially disordered drinking to best plan effective interventions and treatments. SHORT SUMMARY: A CFA of the AUDIT showed good fit for one-, two, and three-factor models overall and by sex in a representative sample in post-conflict Northern Uganda. A three-plus total AUDIT cutoff score is suggested to screen for hazardous drinking in this or similar populations.

The Cedar Project: resilience in the face of HIV vulnerability within a cohort study involving young Indigenous people who use drugs in three Canadian cities.

BACKGROUND: Indigenous scholars have long argued that it is critical for researchers to identify factors related to cultural connectedness that may protect against HIV and hepatitis C infection and buffer the effects of historical and lifetime trauma among young Indigenous peoples. To our knowledge, no previous epidemiological studies have explored the effect of historical and lifetime traumas, cultural connectedness, and risk factors on resilience among young, urban Indigenous people who use drugs. METHODS: This study explored risk and protective factors associated with resilience among participants of the Cedar Project, a cohort study involving young Indigenous peoples who use illicit drugs in three cities in British Columbia, Canada. We utilized the Connor-Davidson Resilience Scale to measure resilience, the Childhood Trauma Questionnaire to measure childhood maltreatment, and the Symptom-Checklist 90-Revised to measure psychological distress among study participants. Multivariate linear mixed effects models (LME) estimated the effect of study variables on mean change in resilience scores between 2011-2012. RESULTS: Among 191 participants, 92 % had experienced any form of childhood maltreatment, 48 % had a parent who attended residential school, and 71 % had been in foster care. The overall mean resilience score was 62.04, with no differences between the young men and women (p = 0.871). Adjusted factors associated with higher mean resilience scores included having grown up in a family that often/always lived by traditional culture (B = 7.70, p = 0.004) and had often/always spoken their traditional language at home (B = 10.52, p < 0.001). Currently knowing how to speak a traditional language (B = 13.06, p = 0.001), currently often or always living by traditional culture (B = 6.50, p = 0.025), and having recently sought drug/alcohol treatment (B = 4.84, p = 0.036) were also significantly associated with higher mean resilience scores. Adjusted factors associated with diminished mean resilience scores included severe childhood emotional neglect (B = -13.34, p = 0.001), smoking crack daily (B = -5.42, p = 0.044), having been sexual assaulted (B = 14.42, p = 0.041), and blackout drinking (B = -6.19, p = 0.027). CONCLUSIONS: Young people in this study have faced multiple complex challenges to their strength. However, cultural foundations continue to function as buffers that protect young Indigenous people from severe health outcomes, including vulnerability to HIV and HCV infection.

HIV vulnerabilities and coercive sex at same-sex sexual debut among men who have sex with men in Beijing, China.

Few studies have examined coercive sex and HIV vulnerabilities among men who have sex with men (MSM) in China. The present study seeks to compare individual characteristics between MSM who did and did not experience coercive sex at their MSM sexual debut and to identify HIV risk factors correlated with coercive sex at MSM sexual debut. In 2007, we recruited 167 MSM in Beijing, China by peer-referred social network sampling. Each participant then completed self-administered questionnaires regarding their sexual experiences and practices. Results show that 14% of participants reported coercive sex at MSM sexual debut, of whom 48% reported recent unprotected anal intercourse (UAI). Coercive sex at MSM sexual debut was significantly associated with UAI [adjusted odds ratio (AOR): 5.38, 95% confidence interval: 1.95-14.87] and lifetime number of male sex partners (AOR: 7.25, 95% CI: 2.39-22.01). Coercive sex is harming MSM in China and should be immediately addressed by researchers, public health officials, and MSM community stakeholders.

"My feelings and my thoughts are my lived experience, not the numbers they show me on a piece of paper": Indigenous experiences of liver transplantation in British Columbia, Canada.

Indigenous Peoples in Canada face healthcare inequities impacting access to solid organ transplantation. The experiences of Indigenous patients during the liver transplant process, and how transplant professionals perceive challenges faced by Indigenous Peoples, has not been studied. Thirteen semi-structured qualitative interviews were conducted via telehealth with Indigenous liver transplant patients (n = 7) and transplant care providers (n = 6) across British Columbia, Canada between April 2021-May 2022. Themes were identified to inform clinical approaches and transplant care planning and validated by Indigenous health experts. Among patient participants: transplants occurred between 1992-2020; all were women; and the mean age at the time of interview was 60 years. Among transplant care provider participants: roles included nursing, social work, and surgery; 83% were women; and the median number of years in transplant care was ten. Three broad themes were identified: Indigenous strengths and resources, systemic and structural barriers, and inconsistent care and cultural safety across health professions impact Indigenous patient care during liver transplantation. This study contributes insights into systemic barriers and Indigenous resilience in the liver transplant journey. Dismantling structural barriers to early linkage to care is needed, and training for transplant clinicians on Indigenous histories, cultural protocols, and cultural safety is strongly recommended.

Overcoming the soul wound: Reflecting on experiences and resilience of intergenerational residential school survivors.

BACKGROUND: Between 1883 and 1996, thousands of Indigenous children were apprehended into Canada's Residential School System. Survivors and their descendants have testified to genocidal harms caused across generations. Yet, Indigenous Peoples continue to exist and resist through inherent resilience described by intergenerational survivors in this paper. OBJECTIVE: This article focuses on stories demonstrating the strength, power, and resilience of intergenerational residential school survivors. PARTICIPANTS & SETTING: Cedar Project is an Indigenous-led cohort study that began as a HIV/AIDS response and contributes to healing among young Indigenous people who use drugs in British Columbia, Canada. It is governed by the Cedar Project Partnership, an Indigenous body of Elders, leaders, and health/social services experts. METHODS: We present qualitative research involving in-depth interviews carried out with Cedar participants who have experienced significant and complex adversities including childhood maltreatment and illicit drug use. Woven throughout, Indigenous scholars who are themselves intergenerational (children and grandchildren) of residential school survivors provide first-person reflections on the findings. RESULTS: Analysis focused on narratives of resilience and resistance to stresses of intergenerational traumas across three broad themes: working to break cycles of intergenerational trauma; foundations of resilience and making positive changes and; hopes and dreams. CONCLUSIONS: Findings establish deeper understanding of processes that enable young people to cope with stresses of intergenerational traumas while facing institutional and structural barriers to wellness. Reflections provide context about how intergenerational experiences intersect with challenges that young intergenerational survivors continue to face. We highlight pathways to healing and sources of strength that inform recommendations for wellness.

The Cedar Project: Racism and its impacts on health and wellbeing among young Indigenous people who use drugs in Prince George and Vancouver, BC.

Racism continues to drive health disparities between Indigenous and non-Indigenous peoples in Canada. This study focuses on racism experienced by young Indigenous people who have used drugs in British Columbia (BC), and predictors of interpersonal racism. Cedar Project is a community-governed cohort study involving young Indigenous people who use drugs in Vancouver and Prince George, BC. This cross-sectional study included data collected between August 2015-October 2016. The Measure of Indigenous Racism Experiences (MIRE) scale was used to assess experiences of interpersonal racism across 9 unique settings on a 5-point Likert scale, collapsing responses into three categories (none/low/high). Multinomial logistic regression models were used to examine associations between key variables and interpersonal racism. Among 321 participants, 79% (n = 255) experienced racism in at least one setting. Thirty two percent (n = 102) experienced high interpersonal racism from police, governmental agencies (child 'welfare', health personnel), and in public settings. Ever having a child apprehended (AOR:2.76, 95%CI:1.14-6.65), probable post-traumatic stress (AOR:2.64; 95%CI:1.08-6.46), trying to quit substances (AOR:3.69; 95%CI:1.04-13.06), leaving emergency room without receiving treatment (AOR:3.05; 95%CI:1.22-7.64), and having a traditional language spoken at home while growing up (AOR:2.86; 95%CI:1.90-6.90) were associated with high interpersonal racism. Among women, experiencing high interpersonal racism was more likely if they lived in Prince George (AOR:3.94; 95%CI:1.07-14.50), ever had a child apprehended (AOR:5.09; 95%CI:1.50-17.30), and had probable post-traumatic stress (AOR:5.21; 95%CI:1.43-18.95). Addressing racism experienced by Indigenous peoples requires immediate structural systemic, and interpersonal anti-racist reforms.

The Cedar Project: high incidence of HCV infections in a longitudinal study of young Aboriginal people who use drugs in two Canadian cities.

BACKGROUND: Factors associated with HCV incidence among young Aboriginal people in Canada are still not well understood. We sought to estimate time to HCV infection and the relative hazard of risk factors associated HCV infection 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 and Prince George, British Columbia, who use illicit drugs. Participants' venous blood samples were drawn and tested for HCV antibodies. Analysis was restricted to participants who use used injection drugs at enrolment or any of follow up visit. Cox proportional hazards regression was used to identify independent predictors of time to HCV seroconversion. RESULTS: In total, 45 out of 148 participants seroconverted over the study period. Incidence of HCV infection was 26.3 per 100 person-years (95% Confidence Interval [CI]: 16.3, 46.1) among participants who reported using injection drugs for two years or less, 14.4 per 100 person-years (95% CI: 7.7, 28.9) among participants who had been using injection drugs for between two and five years, and 5.1 per 100 person-years (95% CI: 2.6,10.9) among participants who had been using injection drugs for over five years. Independent associations with HCV seroconversion were involvement in sex work in the last six months (Adjusted Hazard Ratio (AHR): 1.59; 95% CI: 1.05, 2.42) compared to no involvement, having been using injection drugs for less than two years (AHR: 4.14; 95% CI: 1.91, 8.94) and for between two and five years (AHR: 2.12; 95%CI: 0.94, 4.77) compared to over five years, daily cocaine injection in the last six months (AHR: 2.47; 95% CI: 1.51, 4.05) compared to less than daily, and sharing intravenous needles in the last 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 Aboriginal people in Canada. The HCV incidence rate among Cedar Project participants who were new initiates of injection drug use underscores an urgent need for HCV and injection prevention and safety strategies aimed at supporting young people surviving injection drug use and sex work in both cities. Young people must be afforded the opportunity to provide leadership and input in the development of prevention programming.

The Cedar Project: risk factors for transition to injection drug use among young, urban Aboriginal people.

BACKGROUND: Studies suggest that Aboriginal people in Canada are over-represented among people using injection drugs. The factors associated with transitioning to the use of injection drugs among young Aboriginal people in Canada are not well understood. METHODS: The Cedar Project is a prospective cohort study (2003-2007) involving young Aboriginal people in Vancouver and Prince George, British Columbia, who use illicit drugs. Participants' venous blood samples were tested for antibodies to HIV and the hepatitis C virus, and drug use was confirmed using saliva screens. The primary outcomes were use of injection drugs at baseline and tranisition to injection drug use in the six months before each follow-up interview. RESULTS: Of 605 participants, 335 (55.4%) reported using injection drugs at baseline. Young people who used injection drugs tended to be older than those who did not, female and in a relationship. Participants who injected drugs were also more likely than those who did not to have been denied shelter because of their drug use, to have been incarcerated, to have a mental illness and to have been involved in sex work. Transition to injection drug use occurred among 39 (14.4%) participants, yielding a crude incidence rate of 19.8% and an incidence density of 11.5 participants per 100 person-years. In unadjusted analysis, transition to injection drug use was associated with being female (odds ratio [OR] 1.98, 95% confidence interval (CI) 1.06-3.72), involved in sex work (OR 3.35, 95% CI 1.75-6.40), having a history of sexually transmitted infection (OR 2.01, 95% CI 1.07-3.78) and using drugs with sex-work clients (OR 2.51, 95% CI 1.19-5.32). In adjusted analysis, transition to injection drug use remained associated with involvement in sex work (adjusted OR 3.94, 95% CI 1.45-10.71). INTERPRETATION: The initiation rate for injection drug use of 11.5 participants per 100 person-years among participants in the Cedar Project is distressing. Young Aboriginal women in our study were twice as likely to inject drugs as men, and participants who injected drugs at baseline were more than twice as likely as those who did not to be involved in sex work.

Rates of new HIV diagnoses among Indigenous peoples in Canada, Australia, New Zealand, and the United States: 2009-2017.

OBJECTIVE: To compare rates and trends of HIV diagnoses among Indigenous peoples in Canada (First Nations, Métis, Inuit, and other non-specified), Australia (Aboriginal and Torres Strait Islanders), the USA (American Indian, Alaska Native, Native Hawaiian, and Other Pacific Islanders), and New Zealand (Maori). DESIGN: We employed publicly available surveillance data from 2009 to 2017 to estimate the rate per 100 000 of HIV diagnoses. Estimated annual percentage change (EAPC) in diagnosis rates was calculated using Poisson regression. SETTING: The four countries have passive population-based HIV surveillance programs. PARTICIPANTS: Population estimates from respective census programs were used as rate denominators. MAIN OUTCOME MEASURES: Estimated annual HIV diagnosis rate per 100 000 and EAPC were calculated for total Indigenous peoples, women, and men. RESULTS: As of 2017, rates of HIV were highest in Canada (16.22, 95% confidence interval (CI): 14.30--18.33) and lowest in New Zealand (1.36, 95% CI: 0.65--2.50). Australia had a rate of 3.81 (95% CI: 2.59--5.40) and the USA 3.22 (95% CI: 2.85--3.63). HIV diagnosis rates among the total Indigenous population decreased in Canada (-7.92 EAPC, 95% CI: -9.34 to -6.49) and in the USA (-4.25 EAPC, 95% CI: -5.75 to -2.73) but increased in Australia (5.10 EAPC, 95% CI: 0.39--10.08). No significant trends over time were observed in New Zealand (2.23 EAPC, 95% CI: -4.48 to 9.47). CONCLUSION: Despite limitations to conducting cross-national comparisons, there are substantial differences in HIV diagnosis rates in these four countries that may be reflective of divergent national policies and systems that affect the health status of Indigenous peoples.

The Cedar Project: Historical, structural and interpersonal determinants of involvement in survival sex work over time among Indigenous women who have used drugs in two Canadian cities.

BACKGROUND: Indigenous women involved in survival sex work face multiple layers of discrimination, criminalization and alarming levels of intergenerational and lifetime trauma. This longitudinal study examined historical, structural and interpersonal factors associated with survival sex work involvement among Indigenous women who have used drugs in British Columbia (BC), Canada. METHODS: The Cedar Project is an ongoing cohort study involving young Indigenous people who have used illicit drugs in Vancouver and Prince George, BC. Data was collected every 6 months from 2007 to 2016 . Generalized linear mixed-effects modeling was used to model survival sex work involvement, defined as exchanging sex for money, drugs, food or shelter in the previous six months. RESULTS: Among 292 participants, 34% reported their family always/often lived by traditional culture and 37% reported their family always/often spoke their traditional language. In contrast, 48% had a parent in residential school and 72% were removed from their biological parents. In total, 55% of women were involved in survival sex work at baseline. In adjusted analyses, those who were single (ARR: 1.91; 95% CI: 1.50-2.35), identified as two-spirit (ARR: 2.16; 95% CI: 1.36-2.91), experienced sexual assault (ARR: 1.90; 95% CI: 1.22-2.58), were denied access to shelter (ARR: 1.71; 95% CI: 1.18-2.28), used crack daily (ARR: 2.85; 95% CI: 2.36-3.31), used injection drugs (ARR: 2.52; 95% CI: 1.98-3.07), and were unable to access substance use treatment (ARR: 1.58; 95% CI: 1.15-2.05) were more likely to be involved in sex work. CONCLUSION: Indigenous-governed, wellness-based harm-reduction interventions, and structural reforms addressing housing insecurity and normalization of a culture of violence against Indigenous women, especially those involved in survival sex work, are urgently needed in Canada.

The Cedar Project: exploring the role of colonial harms and childhood maltreatment on HIV and hepatitis C infection in a cohort study involving young Indigenous people who use drugs in two Canadian cities.

OBJECTIVES: This study examined associations between childhood maltreatment, colonial harms and sex/drug-related risks for HIV and hepatitis C virus (HCV) infection among young Indigenous people who use drugs. DESIGN: The Cedar Project is a cohort involving young Indigenous people who use drugs in British Columbia (BC), Canada. Indigenous collaborators, collectively known as the Cedar Project Partnership, govern the entire research process. SETTING: Vancouver is a large city on the traditional territory of the Coast Salish peoples. Prince George is a mid-sized city, on the traditional territory of Lheidli T'enneh First Nation. PARTICIPANTS: 420 participants completed the Childhood Trauma Questionnaire and returned for follow-up from 2003 to 2016. PRIMARY/SECONDARY OUTCOME MEASURES: Primary outcomes were HIV and HCV infection over the study period. Secondary outcomes included sex and substance use-related risks. RESULTS: Prevalence of childhood maltreatment was 92.6% experienced any maltreatment; 73.4% experienced emotional abuse; 62.6% experienced physical abuse; 60.3% experienced sexual abuse; 69.5% experienced emotional neglect and 79.1% experienced physical neglect. We observed significant associations between childhood maltreatment and apprehensions into residential schools and foster care. All maltreatment types were associated with higher odds of sex/substance use-related risks; sexual abuse was associated with higher odds of HCV infection (adjusted OR: 1.67; 95% CI 1.05 to 2.66; p=0.031). CONCLUSIONS: Findings reflect high prevalence of childhood maltreatment and their associations with HIV/HCV risk and HCV infection. Public health prevention and treatment initiatives must be trauma informed and culturally safe to support healing, health, and well-being.

Elevated risk of colorectal, liver, and pancreatic cancers among HCV, HBV and/or HIV (co)infected individuals in a population based cohort in Canada.

INTRODUCTION: Studies of the impact of hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV mono and co-infections on the risk of cancer, particularly extra-hepatic cancer, have been limited and inconsistent in their findings. METHODS: In the British Columbia Hepatitis Testers Cohort, we assessed the risk of colorectal, liver, and pancreatic cancers in association with HCV, HBV and HIV infection status. Using Fine and Gray adjusted proportional subdistribution hazards models, we assessed the impact of infection status on each cancer, accounting for competing mortality risk. Cancer occurrence was ascertained from the BC Cancer Registry. RESULTS: Among 658,697 individuals tested for the occurrence of all three infections, 1407 colorectal, 1294 liver, and 489 pancreatic cancers were identified. Compared to uninfected individuals, the risk of colorectal cancer was significantly elevated among those with HCV (Hazard ration [HR] 2.99; 95% confidence interval [CI] 2.55-3.51), HBV (HR 2.47; 95% CI 1.85-3.28), and HIV mono-infection (HR 2.30; 95% CI 1.47-3.59), and HCV/HIV co-infection. The risk of liver cancer was significantly elevated among HCV and HBV mono-infected and all co-infected individuals. The risk of pancreatic cancer was significantly elevated among individuals with HCV (HR 2.79; 95% CI 2.01-3.70) and HIV mono-infection (HR 2.82; 95% CI 1.39-5.71), and HCV/HBV co-infection. DISCUSSION/CONCLUSION: Compared to uninfected individuals, the risk of colorectal, pancreatic and liver cancers was elevated among those with HCV, HBV and/or HIV infection. These findings highlight the need for targeted cancer prevention and diligent clinical monitoring for hepatic and extrahepatic cancers in infected populations.