"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.

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.

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 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.

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 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.

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.

Impact of HCV infection and ethnicity on incident type 2 diabetes: findings from a large population-based cohort in British Columbia.

INTRODUCTION: Increasing evidence indicates that chronic hepatitis C virus (HCV) infection is associated with higher risk of diabetes. Previous studies showed ethnic disparities in the disease burden of diabetes, with increased risk in Asian population. We described the incidence of type 2 diabetes related to HCV infection and assessed the concurrent impact of HCV infection and ethnicity on the risk of diabetes. RESEARCH DESIGN AND METHODS: In British Columbia Hepatitis Testers Cohort, individuals were followed from HCV diagnosis to the earliest of (1) incident type 2 diabetes, (2) death or (3) end of the study (December 31, 2015). Study population included 847 021 people. Diabetes incidence rates in people with and without HCV were computed. Propensity scores (PS) analysis was used to assess the impact of HCV infection on newly acquired diabetes. PS-matched dataset included 117 184 people. We used Fine and Gray multivariable subdistributional hazards models to assess the effect of HCV and ethnicity on diabetes while adjusting for confounders and competing risks. RESULTS: Diabetes incidence rates were higher among people with HCV infection than those without. The highest diabetes incidence rate was in South Asians with HCV (14.7/1000 person-years, 95% CI 12.87 to 16.78). Compared with Others, South Asians with and without HCV and East Asians with HCV had a greater risk of diabetes. In the multivariable stratified analysis, HCV infection was associated with increased diabetes risk in all subgroups: East Asians, adjusted HR (aHR) 3.07 (95% CI 2.43 to 3.88); South Asians, aHR 2.62 (95% CI 2.10 to 3.26); and Others, aHR 2.28 (95% CI 2.15 to 2.42). CONCLUSIONS: In a large population-based linked administrative health data, HCV infection was associated with higher diabetes risk, with a greater relative impact in East Asians. South Asians had the highest risk of diabetes. These findings highlight the need for care and screening for HCV-related chronic diseases such as type 2 diabetes among people affected by HCV.

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 "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.

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.

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.

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.

Prenatal hepatitis C screening, diagnoses, and follow-up testing in British Columbia, 2008-2019.

OBJECTIVE: Current guidelines in British Columbia recommend prenatal screening for hepatitis C antibodies (anti-HCV) if risk factors are present. We aimed to estimate frequency of prenatal anti-HCV testing, new diagnoses, repeated and follow-up testing among BC women. METHODS: BC Centre for Disease Control Public Health Laboratory data estimated the number of BC women (assigned female at birth or unknown sex) aged 13-49 who received routine prenatal serological screening (HIV, hepatitis B, syphilis and rubella) from 2008-2019. Anti-HCV tests ordered the same day as routine prenatal screens were considered prenatal anti-HCV tests. Assessment of follow-up was based on HCV RNA and/or genotype testing within one year of new prenatal anti-HCV diagnoses. RESULTS: In 2019, 55,202 routine prenatal screens were carried out for 50,392 BC women. Prenatal anti-HCV tests increased significantly, from 19.6% (9,704/49,515) in 2008 to 54.6% (27,516/50,392) in 2019 (p<0.001). New prenatal anti-HCV diagnoses (HCV positive diagnoses at first test or seroconversions) declined from 14.3% in 2008 to 10.1% in 2019. The proportion of women with new prenatal anti-HCV diagnoses that were a result of a first HCV test declined from 0.3% (29/9,701) in 2008 to 0.03% (8/27,500) in 2019. For women known to be anti-HCV positive at the time of prenatal screening, the proportion who had a prenatal anti-HCV test increased from 35.6% in 2008 to 50.8% in 2019. CONCLUSION: Prenatal anti-HCV testing increased substantially over the study period. However, new HCV diagnoses remained relatively stable, suggesting that a considerable proportion of BC women with low or no risk are being screened as part of prenatal care. The vast majority of women with new HCV diagnoses receive appropriate follow-up HCV RNA and genotype testing, which may indicate interest in HCV treatment. These findings contribute to the discussion around potential for prenatal anti-HCV screening in an effort to eliminate HCV.

Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada.

BACKGROUND: The majority of new HCV infections in Canada occur in people who inject drugs. Thus, while curative direct antiviral agents (DAAs) herald a promising new era in hepatitis C virus (HCV) treatment, improving the lives and wellbeing of people living with HCV (PLHCV) must be considered in the context of reducing overdose-related harms and with a syndemic lens. We measure drug-related deaths (DRDs) among HCV-negative people and PLHCV in British Columbia (BC), Canada, and the impact of potent contaminants like fentanyl on deaths. METHODS: We identified DRDs among PLHCV and HCV-negative individuals from 2010 to 2018 in the BC Hepatitis Testers Cohort, a population-based dataset of ~1.7 million British Columbians comprising comprehensive administrative and clinical data. We estimated annual standardized liver- and drug-related mortality rates per 100,000 person-years (PY) and described the contribution of specific drugs, including fentanyl and its analogues, implicated in DRDs over time. RESULTS: DRDs constituted 20.1% of deaths among PLHCV and 4.7% of deaths among HCV-negative individuals; a 4.3-fold (95% confidence interval: 4.0-4.5) difference. Drug-related mortality overtook liver-related mortality for PLHCV in 2015 and HCV-negative individuals in 2016 and rose from 241.7 to 436.5 per 100,000 PY from 2010 to 2018 amongPLHCV and from 20.0 to 57.1 per 100,000 PY for HCV-negative individuals over the same period. The proportion of deaths attributable to drugs among PLHCV and HCV-negative individuals increased from 15.1% to 26.1% and 3.1% to 8.0%, in 2010 and 2018, respectively. The proportion of DRDs attributed solely to synthetic opioids such as fentanyl averaged across both groups increased from 2.1% in 2010 to 69.6% in 2017. CONCLUSION: Steep drug-related mortality increases among PLHCV and HCV-negative individuals over the last decade highlight the urgent need to address overdose-related drivers and harms in these populations using an integrated care approach.

Syndemic profiles of people living with hepatitis C virus using population-level latent class analysis to optimize health services.

BACKGROUND: Hepatitis C (HCV) affects diverse populations such as people who inject drugs (PWID), 'baby boomers,' gay/bisexual men who have sex with men (gbMSM), and people from HCV endemic regions. Assessing HCV syndemics (i.e.relationships with mental health/chronic diseases) among subpopulations using Latent Class Analysis (LCA) may facilitate targeted program planning. METHODS: The BC Hepatitis Testers Cohort(BC-HTC) includes all HCV cases identified in BC between 1990 and 2015, integrated with medical administrative data. LCA grouped all BC-HTC HCV diagnosed people(n = 73,665) by socio-demographic/clinical indicators previously determined to be relevant for HCV outcomes. The final model was chosen based on fit statistics, epidemiological meaningfulness, and posterior probability. Classes were named by most defining characteristics. RESULTS: The six-class model was the best fit and had the following names and characteristics: 'Younger PWID'(n =11,563): recent IDU (67%), people born >1974 (48%), mental illness (62%), material deprivation (59%). 'Older PWID'(n =15,266): past IDU (78%), HIV (17%), HBV (17%) coinfections, alcohol misuse(68%). 'Other Middle-Aged People'(n = 9019): gbMSM (26%), material privilege (31%), people born between 1965-1974 (47%). 'People of Asian backgrounds' (n = 4718): East/South Asians (92%), no alcohol misuse (97%) or mental illness (93%), people born <1945 (26%), social privilege (66%). 'Rural baby boomers' (n = 20,401): rural dwellers (32%), baby boomers (79%), heterosexuals (99%), no HIV (100%). 'Urban socially deprived baby boomers' (n = 12,698): urban dwellers (99%), no IDU (100%), liver disease (22%), social deprivation (94%). CONCLUSIONS: Differences between classes suggest variability in patients' service needs. Further analysis of health service utilization patterns may inform optimal service layout.

The Cedar Project - Mobile Phone Use and Acceptability of Mobile Health Among Young Indigenous People Who Have Used Drugs in British Columbia, Canada: Mixed Methods Exploratory Study.

BACKGROUND: Indigenous leaders continue to be concerned about high rates of HIV and barriers to HIV treatment among young Indigenous people involved in substance use. Growing evidence suggests that using mobile phones for health (mHealth) may be a powerful way to support connection with health services, including HIV prevention and treatment. OBJECTIVE: This study examined the patterns of mobile phone ownership and use among young Indigenous people who have used drugs living with or vulnerable to HIV and explored the acceptability of mHealth to support access to health care in this population. METHODS: The Cedar Project is a cohort study involving young Indigenous people who have used drugs in Vancouver and Prince George, British Columbia. This mixed methods exploratory study involved 131 Cedar Project participants enrolled in our WelTel mHealth program. At enrollment, participants completed a questionnaire related to mobile phone use and interest in mHealth. Data were linked to Cedar Project questionnaires and serodata. We present comparative statistics (quantitative) and results of a rapid thematic analysis (qualitative) related to mobile phone patterns and interest in receiving mHealth. RESULTS: Less than half of the participants (59/130; 45.4%) reported owning a phone. Among those with a phone, the majority owned a smartphone (46/59; 78%). Most participants with a phone reported having an unlimited texting plan (39/55; 71%), using the internet on their phone (44/59; 75%), and texting daily (44/55; 80%). A majority reported that using a mobile phone for health would be invaluable (120/130; 92.3%). There were no differences in mHealth acceptance between participants who owned a phone and those who did not (P>.99). All but one participant living with HIV felt using a mobile phone would be helpful for their health, while a small proportion of HIV-negative participants remained unsure (1.9% vs 11.7%; P=.047). In response to open-ended questions asking why using a mobile phone may be helpful for health, participants identified a diverse set of anticipated benefits: (1) connection for emotional, mental, and spiritual support, (2) connection to family, (3) staying in touch and/or being reachable, (4) overcoming current barriers to phone use, (5) convenience, privacy, and safety, and (6) access to health care and emergency services. CONCLUSIONS: We observed high acceptance and interest in using mobile phone technology for health despite low rates of personal mobile phone connectivity among young Indigenous people who have used drugs living with and vulnerable to HIV in British Columbia, Canada. Mobile phones were viewed as a way to support connections and relationships that are seen as critical to health and well-being among young Indigenous people in this study. Findings may be useful for health care providers preparing to scale up mHealth programs to support HIV prevention and treatment in this population.

Real-world Effectiveness of Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C in British Columbia, Canada: A Population-Based Cohort Study.

BACKGROUND: Clinical trials show high efficacy of sofosbuvir/velpatasvir (SOF/VEL), but there are limited data from "real-world" settings. We aimed to evaluate SOF/VEL effectiveness for all hepatitis C virus (HCV) genotypes (GTs) in British Columbia (BC), Canada. METHODS: We used the BC Hepatitis Testers Cohort, which includes all HCV cases in the province (1990-2015) linked to administrative databases, including prescriptions to end of 2018. We measured sustained virologic response (SVR; negative RNA ≥10 weeks after treatment end) and identified characteristics associated with non-SVR. Conservatively, we excluded individuals with no assessment for SVR if their last RNA test after treatment initiation was negative (but included if positive). RESULTS: Of 2821 eligible participants, most were infected with GT1 (1076, 38.1%) or GT3 (1072, 38.0%), and a minority (278, 9.9%) were treated with RBV. SVR was 94.6% (2670/2821) overall and 94.5% (1017/1076) for GT1, 96.4% (512/531) for GT2, and 93.7% (1004/1072) for GT3. When disaggregated by GT, treatment regimen, and cirrhosis/treatment experience, SVR was lowest (30/40, 75.0%) among treatment-experienced GT3 individuals treated with RBV. Characteristics associated with non-SVR in multivariable analysis included younger age, RBV addition, and being a person with HIV (PWH) or who injects/injected drugs (PWID). When treatment regimen (±RBV) was removed from multivariable model, treatment experience was associated with non-SVR for GT3. Of 151 non-SVR individuals, 56.3% were nonvirological failures (treatment incomplete/no assessment for SVR) and 43.7% were virological failures (nonresponse/relapse). A disproportionately high percentage of non-SVR among PWID was due to nonvirological failure. CONCLUSIONS: SOF/VEL was highly effective in this "real-world" population-based cohort. Additional support is required for PWID/PWH to reach SVR.

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.