Documents de recherche

@article{Young2023,
title = {The rate of hepatitis C reinfection in Canadians coinfected with HIV and its implications for national elimination},
author = {Jim Young, Shouao Wang, Charlotte Lanièce Delaunay, Curtis L Cooper, Joseph Cox, M John Gill, Mark Hull, Sharon Walmsley, Alexander Wong , Marina B Klein; Canadian Coinfection Cohort Investigators},
doi = {10.1016/j.drugpo.2023.103981},
year = {2023},
date = {2023-04-01},
journal = {Int J Drug Policy },
volume = {114},
number = {103981},
pages = {103981},
abstract = {Background: The World Health Organisation (WHO) has set targets for the rate of new infections as a way to measure progress towards the elimination of hepatitis C virus (HCV) as a public health threat. As more people are successfully treated for HCV, a higher proportion of new infections will be reinfections. We consider whether the reinfection rate has changed since the interferon era and what we can infer about national elimination efforts from the current reinfection rate.

Methods: The Canadian Coinfection Cohort is representative of HIV HCV coinfected people in clinical care. We selected cohort participants successfully treated for a primary HCV infection either in the interferon era or in the era of direct acting antivirals (DAAs). Selected participants were followed from 12 weeks after completing a successful treatment until the end of 2019 or until their last measured HCV RNA. We estimated the reinfection rate in each treatment era, overall and in participant subgroups, using proportional hazard models appropriate for interval censored data.

Results: Among 814 successfully treated participants with additional HCV RNA measurements, there were 62 reinfections. The overall reinfection rate was 2.6 (95% confidence interval, CI, 1.2-4.1) /100 person years (PY) in the interferon era and 3.4 (95% CI 2.5-4.4) /100 PY in the DAA era. The rate in those reporting injection drug use (IDU) was much higher: 4.7 (95% CI 1.4-7.9) /100 PY and 7.6 (95% CI 5.3-10) /100 PY in the interferon and DAA eras respectively.

Conclusion: The overall reinfection rate in our cohort is now above the WHO target set for new infections in people who inject drugs. The reinfection rate in those reporting IDU has increased since the interferon era. This suggests Canada is not on track to achieve HCV elimination by 2030.},
keywords = {HCV Elimination, HCV elimination; HCV reinfection; HCV treatment; HIV-HCV coinfection; People who inject drugs, HCV reinfection, HCV treatment, HIV-HCV coinfection, People who inject drugs},
pubstate = {published},
tppubtype = {article}
}

@article{D2022b,
title = {Interventions to improve uptake of direct-acting antivirals for hepatitis C virus in priority populations: A systematic review},
author = {D, Ortiz-Paredes; A, Amoako; T, Ekmekjian; K, Engler; B, Lebouché; MB, Klein;},
doi = {10.3389/fpubh.2022.877585},
year = {2022},
date = {2022-06-24},
journal = {Frontiers in Public Health},
abstract = {Background & objective: Access to Hepatitis C (HCV) care remains suboptimal. This systematic review sought to identify existing interventions designed to improve direct-acting antiviral (DAA) uptake among HCV infected women, people who inject drugs (PWID), men who have sex with men (MSM), and Indigenous peoples.

Methods: Studies published in high- and middle-income countries were retrieved from eight electronic databases and gray literature (e.g., articles, research reports, theses, abstracts) were screened by two independent reviewers. Identified interventions were summarized using textual narrative synthesis.

Results: After screening 3,139 records, 39 studies were included (11 controlled comparative studies; 36 from high-income countries). Three groups of interventions were identified: interventions involving patients; providers; or the healthcare system. Interventions directed to patients included care co-ordination, accelerated DAA initiation, and patient education. Interventions involving providers included provider education, telemedicine, multidisciplinary teams, and general practitioner-led care. System-based interventions comprised DAA universal access policies and offering HCV services in four settings (primary care, secondary care, tertiary care, and community settings). Most studies (30/39) described complex interventions, i.e., those with two or more strategies combined. Most interventions (37/39) were tailored to, or studied among, PWID. Only one study described an intervention that was aimed at women.

Conclusions: Combining multiple interventions is a common approach for supporting DAA initiation. Three main research gaps were identified, specifically, a lack of: (1) controlled trials estimating the individual or combined effects of interventions on DAA uptake; (2) studies in middle-income countries; and (3) interventions tailored to women, MSM, and Indigenous people.},
keywords = {antiviral agents, hepatitis C, Indigenous peoples, People who inject drugs, sexual and gender minorities},
pubstate = {published},
tppubtype = {article}
}

@article{C2022,
title = {Gaps in hepatitis C virus prevention and care for HIV-hepatitis C virus co-infected people who inject drugs in Canada},
author = {C, Laniece Delaunay; M, Maheu-Giroux; G, Marathe; S, Saeed S; V, Martel-Laferriere; C, Cooper; S, Walmsley; J, Cox; A, Wong A; MB, Klein; },
url = {https://www.sciencedirect.com/science/article/pii/S0955395922000470?via%3Dihub},
doi = {10.1016/j.drugpo.2022.103627},
year = {2022},
date = {2022-02-01},
journal = {International Journal of Drug Policy},
abstract = {Background: People who inject drugs (PWID) living with HIV are a priority population for eliminating hepatitis C virus (HCV) as a public health threat. Maximizing access to HCV prevention and treatment strategies are key steps towards elimination. We aimed to evaluate engagement in harm reduction programs and HCV treatment, and to describe injection practices among HIV-HCV co-infected PWID in Canada from 2003 to 2019.

Methods: We included Canadian Coinfection Cohort study participants who reported injecting drugs between 2003 and 2019 in Quebec, Ontario, Saskatchewan, and British Columbia, Canada. We investigated temporal trends in HCV treatment uptake, efficacy, and effectiveness; injection practices; and engagement in harm reduction programs in three time periods based on HCV treatment availability: 1) interferon/ribavirin (2003-2010); 2) first-generation direct acting antivirals (DAAs) (2011-2013); 3) second-generation DAAs (2014-2019). Harm reduction services assessed included needle and syringe programs (NSP), opioid agonist therapy (OAT), and supervised injection sites (SIS).

Results: Median age of participants (N = 1,077) at cohort entry was 44 years; 69% were males. Province-specific HCV treatment rates increased among HCV RNA-positive PWID, reaching 16 to 31 per 100 person-years in 2014-2019. Treatment efficacy improved from a 50 to 70% range in 2003-2010 to >90% across provinces in 2014-2019. Drug injecting patterns among active PWID varied by province, with an overall decrease in cocaine injection frequency and increasing opioid injections. In the most recent time period (2014-2019), needle/syringe sharing was reported at 8-22% of visits. Gaps remained in engagement in harm reduction programs: NSP use decreased (58-70% of visits), OAT engagement among opioid users was low (8-26% of visits), and participants rarely used SIS (1-15% of visits).

Conclusion: HCV treatment uptake and outcomes have improved among HIV-HCV coinfected PWID. Yet, this population remains exposed to drug-related harms, highlighting the need to tie HCV elimination strategies with enhanced harm reduction programs to improve overall health for this population.},
keywords = {drug injecting patterns, harm reduction, HCV Elimination, HCV treatment, HIV-HCV coinfection, People who inject drugs},
pubstate = {published},
tppubtype = {article}
}

@article{D2021b,
title = {Barriers and facilitators related to HCV treatment uptake among HIV coinfected populations in Canada: Patients and treatment provider perceptions},
author = {D, Ortiz-Paredes; A, Amoako; D, Lessard; K, Engler; B, Lebouché; M, Klein; },
url = {https://canlivj.utpjournals.press/doi/full/10.3138/canlivj-2021-0020},
doi = {10.3138/canlivj-2021-0020},
year = {2021},
date = {2021-12-01},
journal = {Canadian Liver Journal},
abstract = {BACKGROUND: Direct-acting antiviral (DAA) uptake is challenging across HIV-hepatitis C (HCV) coinfected populations. This study sought to identify barriers and facilitators related to DAA uptake in priority populations in Canada. METHODS: This qualitative descriptive study included 11 people living with HIV with a history of HCV and 15 HCV care providers. Participants were part of either nominal groups (n = 4) or individual interviews (n = 6) in which they identified and ranked barriers and facilitators to DAA uptake. Consolidated lists of barriers and facilitators were identified thematically. RESULTS: Patient participants highly ranked the following barriers: competing priorities and needs (ie, social instability and mental health), delays in care, lack of adherence, and polypharmacy. Provider participant top barriers were the following: competing priorities and needs (ie, social chaos), delays in care (eg, systemic barriers, difficulties engaging patients, lack of trained HCV providers), and HCV-related stigma. Patient participants identified having a strong network of health care providers, family, and friends, possessing intrinsic motivation, and DAAs being a simple and tolerable oral treatment as important facilitators. Provider participant top-ranked facilitators were having resources to identify hard-to-reach populations (eg, patient navigation, outreach), holistic care and addiction management, provider HCV education, and a strong network of interprofessional collaboration. CONCLUSION: The barriers to DAA initiation addressed by patients and providers overlapped, with some nuances. Multidisciplinary care fostering a strong supportive network and intrinsically motivated patients along with HCV education emerged as key facilitators. This study provides insights for developing potential strategies to improve DAA uptake among HIV-HCV coinfected people in Canada.},
keywords = {direct-acting antivirals uptake, hepatitis C, men who have sex with men, MSM, People who inject drugs},
pubstate = {published},
tppubtype = {article}
}

@article{D2021,
title = {Potential interventions to support HCV treatment uptake among HIV co-infected people in Canada: Perceptions of patients and health care providers},
author = {D, Ortiz-Paredes; A, Amoako; D, Lessard; K, Engler; B, Lebouché; M, Klein; },
url = {https://canlivj.utpjournals.press/doi/full/10.3138/canlivj-2021-0021},
doi = {10.3138/canlivj-2021-0021},
year = {2021},
date = {2021-11-05},
journal = {Canadian Liver Journal},
abstract = {BACKGROUND: Increasing direct-acting antiviral (DAA) treatment uptake is key to eliminating HCV infection as a public health threat in Canada. People living with human immunodeficiency virus (HIV) and hepatitis C (HCV) co-infection face barriers to HCV treatment initiation. We sought to identify interventions that could support HCV treatment initiation based on patient and HCV care provider perspectives. METHODS: Eleven people living with HIV with a history of HCV infection and 12 HCV care providers were recruited for this qualitative descriptive study. Participants created ranked-ordered lists of potential interventions during nominal groups (n = 4) and individual interviews (n = 6). Following the nominal group technique, transcripts and intervention lists underwent thematic analysis and ranking scores were merged to create consolidated and prioritized lists from patient and provider perspectives. RESULTS: Patient participants identified a total of eight interventions. The highest-ranked interventions were multidisciplinary clinics, HCV awareness campaigns and patient education, nurse- or pharmacist-led care, peer involvement, and more and better-prepared health professionals. Provider participants identified 11 interventions. The highest-ranked were mobile outreach, DAA initiation at pharmacies, a simplified process of DAA prescription, integration of primary and specialist care, and patient-centred approaches. CONCLUSION: Participants proposed alternatives to hospital-based specialist HCV care, which require increasing capacity for nurses, pharmacists, primary care providers, and peers to have more direct roles in HCV treatment provision. They also identified the need for structural changes and educational initiatives. In addition to optimizing HCV care, these interventions might result in broader benefits for the health of HIV–HCV co-infected people.},
keywords = {Direct-acting antivirals, hepatitis C, HIV infection, Indigenous peoples, men who have sex with men, People who inject drugs, Treatment uptake, Women},
pubstate = {published},
tppubtype = {article}
}

@article{A2021,
title = {Estimating an individual-level deprivation index for HIV/HCV coinfected persons in Canada},
author = {A, Palayew; AM, Schmidt; S, Saeed; CL Cooper; A, Wong; V, Martel-Laferrière; S, Walmsley; J, Cox; MB, Klein;},
url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249836},
doi = {10.1371/journal.pone.0249836},
year = {2021},
date = {2021-04-19},
journal = {PLOS One},
abstract = {Background
HIV-HCV coinfected individuals are often more deprived than the general population. However, deprivation is difficult to measure, often relying on aggregate data which does not capture individual heterogeneity. We developed an individual-level deprivation index for HIV-HCV co-infected persons that encapsulated social, material, and lifestyle factors.

Methods
We estimated an individual-level deprivation index with data from the Canadian Coinfection Cohort, a national prospective cohort study. We used a predetermined process to select 9 out of 19 dichotomous variables at baseline visit to include in the deprivation model: income >$1500/month; education >high school; employment; identifying as gay or bisexual; Indigenous status; injection drug use in last 6 months; injection drug use ever; past incarceration, and past psychiatric hospitalization. We fitted an item response theory model with: severity parameters (how likely an item was reported), discriminatory parameters, (how well a variable distinguished index levels), and an individual parameter (the index). We considered two models: a simple one with no provincial variation and a hierarchical model by province. The Widely Applicable Information Criterion (WAIC) was used to compare the fitted models. To showcase a potential utility of the proposed index, we evaluated with logistic regression the association of the index with non-attendance to a second clinic visit (as a proxy for disengagement) and using WAIC compared it to a model containing all the individual parameters that compose the index as covariates.

Results
We analyzed 1547 complete cases of 1842 enrolled participants. According to the WAIC the hierarchical model provided a better fit when compared to the model that does not consider the individual’s province. Values of the index were similarly distributed across the provinces. Overall, past incarceration, education, and unemployment had the highest discriminatory parameters. However, in each province different components of the index were associated with being deprived reflecting local epidemiology. For example, Saskatchewan had the highest severity parameter for Indigenous status while Quebec the lowest. For the secondary analysis, 457 (30%) failed to attend a second visit. A one-unit increase in the index was associated with 17% increased odds (95% credible interval, 2% to 34%) of not attending a second visit. The model with just the index performed better than the model with all the components as covariates in terms of WAIC.

Conclusion
We estimated an individual-level deprivation index in the Canadian Coinfection cohort. The index identified deprivation profiles across different provinces. This index and the methodology used may be useful in studying health and treatment outcomes that are influenced by social disparities in co-infected Canadians. The methodological approach described can be used in other studies with similar characteristics.},
keywords = {Hepatitis C virus, HIV, HIV-HCV co-infection, Injection drug use, People who inject drugs},
pubstate = {published},
tppubtype = {article}
}

@article{S2020,
title = {Eliminating Structural Barriers: The Impact of Unrestricted Access on Hepatitis C Treatment Uptake Among People Living With Human Immunodeficiency Virus},
author = {Saeed S and Strumpf E and Moodie EEM and Wong L and Cox J and Walmsley S and Tyndall M and Cooper C and Conway B and Hull M and Martel-Laferriere V and Gill MJ and Wong A and Vachon ML and Klein MB and for the Canadian Co-Infection Cohort Study Investigators},
url = {https://pubmed.ncbi.nlm.nih.gov/31504327/},
doi = {10.1093/cid/ciz833},
year = {2020},
date = {2020-07-11},
journal = {Clinical Infectious Diseases},
abstract = {Background: High costs of direct-acting antivirals (DAAs) have led health-care insurers to limit access worldwide. Using a natural experiment, we evaluated the impact of removing fibrosis stage restrictions on hepatitis C (HCV) treatment initiation rates among people living with human immunodeficiency virus (HIV), and then examined who was left to be treated.

Methods: Using data from the Canadian HIV-HCV Coinfection Cohort, we applied a difference-in-differences approach. Changes in treatment initiation rates following the removal of fibrosis stage restrictions were assessed using a negative binomial regression with generalized estimating equations. The policy change was then specifically assessed among people who inject drugs (PWID). We then identified the characteristics of participants who remained to be treated using a modified Poisson regression.

Results: Between 2010-2018, there were a total of 585 HCV initiations among 1130 eligible participants. After removing fibrosis stage restrictions, DAA initiations increased by 1.8-fold (95% confidence interval [CI] 1.3-2.4) controlling for time-invariant differences and secular trends. Among PWID the impact appeared even stronger, with an adjusted incidence rate ratio of 3.6 (95% CI 1.8-7.4). However, this increased treatment uptake was not sustained. At 1 year following universal access, treatment rates declined to 0.8 (95% CI .5-1.1). Marginalized participants (PWID and those of indigenous ethnicity) and those disengaged from care were more likely to remain HCV RNA positive.

Conclusions: After the removal of fibrosis restrictions, HCV treatment initiations nearly doubled immediately, but this treatment rate was not sustained. To meet the World Health Organization elimination targets, the minimization of structural barriers and adoption of tailored interventions are needed to engage and treat all vulnerable populations.},
keywords = {Direct acting antivirals (DAAs), HIV-HCV co-infection, People who inject drugs, Quasi-experimental methods, Unrestricted access},
pubstate = {published},
tppubtype = {article}
}

@article{Saeed2016,
title = {How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World?},
author = {Sahar Saeed and Erin C. Strumpf and Sharon Walmsley and Kathleen C. Rollet-Kurhajec and Neora Pick and Valerie Martel-Laferrière and Mark Hull and John Gill and Joseph Cox and Curtis Cooper and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26743093},
doi = {10.1093/cid/civ1222},
year = {2016},
date = {2016-04-15},
journal = {Clinical Infectious Diseases},
abstract = {BACKGROUND:
Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have been described as revolutionary. However, it remains uncertain how effective these drugs will be for individuals coinfected with human immunodeficiency virus (HIV)-HCV. Bridging this gap between efficacy and effectiveness requires a focus on the generalizability of clinical trials.
METHODS:
Generalizability of DAA trials was assessed by applying the eligibility criteria from 5 efficacy trials: NCT01479868, PHOTON-1 (NCT01667731), TURQUOISE-I (NCT01939197), ION-4 (NCT02073656), and ALLY-2 (NCT02032888) that evaluated simeprevir; sofosbuvir; ombitasvir, paritaprevir/ritonavir/dasabuvir; sofosbuvir/ledipasvir; and daclatasvir/sofosbuvir, respectively, to the Canadian Coinfection Cohort, representing approximately 23% of the total coinfected population in care in Canada.
RESULTS:
Of 874 active participants, 70% had chronic HCV, of whom 410, 26, 94, and 11 had genotypes 1, 2, 3, and 4, respectively. After applying trial eligibility criteria, only 5.9% (24/410) would have been eligible for enrollment in the simeprevir trial, 9.8% (52/530) in PHOTON-1, 6.3% (26/410) in TURQUOISE-I, and 8.1% (34/421) in ION-4. The ALLY-2 study was more inclusive; 43% (233/541) of the cohort would have been eligible. The most exclusive eligibility criteria across all trials with the exception of ALLY-2 were restriction to specific antiretroviral therapies (63%-79%) and active illicit drug use (53%-55%).
CONCLUSIONS:
DAA trial results may have limited generalizability, since the majority of coinfected individuals were not eligible to participate. Exclusions appeared to be related to improving treatment outcomes by not including those at higher risk of poor adherence and reinfection--individuals for whom real-world data are urgently needed.
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.},
keywords = {Clinical trials, Direct-acting antivirals, Generalizability, HIV–hepatitis C coinfection, People who inject drugs},
pubstate = {published},
tppubtype = {article}
}