Documents de recherche

@article{N2021,
title = {Liver Fibrosis in Human Immunodeficiency Virus (HIV)-Hepatitis C Virus (HCV) Coinfection Before and After Sustained Virologic Response: What Is the Best Noninvasive Marker for Monitoring Regression?},
author = {N, Kronfli; J, Young; S, Wang; J, Cox; S, Walmsley; M, Hull; C, Cooper; V, Martel-Laferriere; A, Wong; N, Pick; MB, Klein; Canadian Coinfection Cohort Study Investigators.},
url = {https://academic.oup.com/cid/article/73/3/468/5854053?login=false},
doi = {10.1093/cid/ciaa702},
year = {2021},
date = {2021-08-02},
journal = {Clinical Infectious Diseases},
abstract = {Background: Noninvasive markers of liver fibrosis such as aspartate aminotransferase-to-platelet ratio (APRI) and transient elastography (TE) have largely replaced liver biopsy for staging hepatitis C virus (HCV). As there is little longitudinal data, we compared changes in these markers before and after sustained virologic response (SVR) in human immunodeficiency virus (HIV)-HCV coinfected patients.

Methods: Participants from the Canadian Coinfection Cohort study who achieved SVR after a first treatment with either interferon/ribavirin or direct acting antivirals (DAAs), with at least 1 pre- and posttreatment fibrosis measure were selected. Changes in APRI or TE (DAA era only) were modeled using a generalized additive mixed model, assuming a gamma distribution and adjusting for sex, age at HCV acquisition, duration of HCV infection, and time-dependent body mass index, binge drinking, and detectable HIV RNA.

Results: Of 1981 patients, 151 achieved SVR with interferon and 553 with DAAs; 94 and 382 met inclusion criteria, respectively. In the DAA era, APRI increased (0.03 units/year; 95% credible interval (CrI): -.05, .12) before, declined dramatically during, and then changed minimally (-0.03 units/year; 95% CrI: -.06, .01) after treatment. TE values, however, increased (0.74 kPa/year; 95% CrI: .36, 1.14) before treatment, changed little by the end of treatment, and then declined (-0.55 kPa/year; 95% CrI: -.80, -.31) after SVR.

Conclusions: TE should be the preferred noninvasive tool for monitoring fibrosis regression following cure. Future studies should assess the risk of liver-related outcomes such as hepatocellular carcinoma according to trajectories of fibrosis regression measured using TE to determine if and when it will become safe to discontinue screening.},
keywords = {APRI, Fibrosis regression, HIV-HCV coinfection, Sustained virologic response, Transient elastography},
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{W2020,
title = {The Mediating Role of Depressive Symptoms in the Association Between Food Insecurity and HIV Related Health Outcomes Among HIV-HCV Co-Infected People},
author = {Aibibula W and Cox J and Hamelin AM and Klein MB and Brassard P},
url = {https://pubmed.ncbi.nlm.nih.gov/31950306/},
doi = {10.1007/s10461-020-02784-7},
year = {2020},
date = {2020-07-01},
journal = {AIDS and Behaviour},
abstract = {Food insecurity may lead to depressive symptoms, which are known to be associated with poor HIV related health outcomes. However, it is unclear to what extent food insecurity 'directly' affects these outcomes. We used data from the Food Security & HIV-HCV Sub-Study of the Canadian Co-Infection Cohort to assess the controlled direct effect. People experiencing severe food insecurity had 1.47 (95% CI 1.04-2.09) times the risk of having detectable HIV viral load and 0.94 (95% CI 0.87-1.02) fold change in CD4 count. After holding depressive symptoms constant, the association between severe food insecurity and HIV viral load was attenuated to a statistically non-significant level (RR 1.36, 95% CI: 0.95-1.96), whereas the association between severe food insecurity and CD4 count was unchanged. Depressive symptoms partially mediate the effect of severe food insecurity on HIV viral suppression; interventions focused on depressive symptoms alone may not be sufficient, however, to eliminate this effect.},
keywords = {CD4 count, Food insecurity, HIV viral load, HIV-HCV co-infection, Mediation analysis},
pubstate = {published},
tppubtype = {article}
}

@article{Kronfli2020,
title = {Liver fibrosis in HIV-Hepatitis C virus (HCV) co-infection before and after sustained virologic response: what is the best non-invasive marker for monitoring regression?},
author = {Nadine Kronfli and Jim Young and Shouao Wang and Joseph Cox and Sharon Walmsley and Mark Hull and Curtis Cooper and Valerie Martel-Laferriere and Alexander Wong and Neora Pick and Marina B Klein and Canadian Co-infection Cohort Study Investigators},
url = {https://pubmed.ncbi.nlm.nih.gov/32504083/},
doi = {10.1093/cid/ciaa702},
year = {2020},
date = {2020-06-05},
journal = {Clinical Infectious Diseases},
abstract = {Background: Noninvasive markers of liver fibrosis such as aspartate aminotransferase-to-platelet ratio (APRI) and transient elastography (TE) have largely replaced liver biopsy for staging hepatitis C virus (HCV). As there is little longitudinal data, we compared changes in these markers before and after sustained virologic response (SVR) in HIV-HCV coinfected patients.

Methods: Participants from the Canadian Coinfection Cohort study who achieved SVR after a first treatment with either interferon/ribavirin or direct acting antivirals (DAAs), with at least one pre- and post-treatment fibrosis measure were selected. Changes in APRI or TE (DAA era only) were modelled using a generalised additive mixed model, assuming a gamma distribution and adjusting for sex, age at HCV acquisition, duration of HCV infection, and time-dependent BMI, binge drinking and detectable HIV RNA.

Results: Of 1981 patients, 151 achieved SVR with interferon and 553 with DAAs; 94 and 382 met inclusion criteria, respectively. In the DAA era, APRI increased (0.03 units/year; 95% credible interval (CrI): -0.05, 0.12) before, declined dramatically during, and then changed minimally (-0.03 units/year; 95% CrI: -0.06, 0.01) after treatment. TE values, however, increased (0.74 kPa/year; 95% CrI: 0.36, 1.14) before treatment, changed little by the end of treatment, and then declined (-0.55 kPa/year; 95% CrI: -0.80, -0.31) after SVR.

Conclusions: TE should be the preferred non-invasive tool for monitoring fibrosis regression following cure. Future studies should assess the risk of liver-related outcomes such as hepatocellular carcinoma according to trajectories of fibrosis regression measured using TE to determine if and when it will become safe to discontinue screening.},
keywords = {APRI, Fibrosis regression, HIV-HCV co-infection, Sustained virologic response, Transient elastography},
pubstate = {published},
tppubtype = {article}
}

@article{ME2019,
title = {"Another thing to live for": Supporting HCV treatment and cure among Indigenous people impacted by substance use in Canadian cities},
author = {Pearce ME and Jongbloed K and Demeras L and MacDonald H and Christian WM and Sharma R and Pick N and Yoshida EM and Spittal PM and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/31525640/},
doi = {10.1016/j.drugpo.2019.08.003},
year = {2019},
date = {2019-12-01},
journal = {The International Journal on Drug Policy},
abstract = {Background: Colonization and colonial systems have led to the overrepresentation of Indigenous people impacted by substance use and HCV infection in Canada. It is critical to ensure Indigenous people's equitable access to new direct acting antiviral HCV treatments (DAAs). Identifying culturally-safe, healing-centered approaches that support the wellbeing of Indigenous people living with HCV is an essential step toward this goal. We listened to the stories and perspectives of HCV-affected Indigenous people and HCV treatment providers with the aim of providing pragmatic recommendations for decolonizing HCV care.

Methods: Forty-five semi-structured interviews were carried out with Indigenous participants affected by HCV from the Cedar Project (n = 20, British Columbia (BC)) and the Canadian Coinfection Cohort (n = 25, BC; Ontario (ON); Saskatchewan (SK)). In addition, 10 HCV treatment providers were interviewed (n = 4 BC, n = 4 ON, n = 2 SK). Interpretive description identified themes to inform clinical approaches and public health HCV care. Themes and related recommendations were validated by Indigenous health experts and Indigenous participants prior to coding and re-contextualization.

Results: Taken together, participants' stories and perceptions were interpreted to coalesce into three overarching and interdependent themes representing their recommendations. First: treatment providers must understand and accept colonization as a determinant of health and wellness among HCV-affected Indigenous people, including ongoing cycles of child apprehension and discrimination within the healthcare system. Second: consistently safe attitudes and actions create trust within HCV treatment provider-patient relationships and open opportunities for engagement into care. Third: treatment providers who identify, build, and strengthen circles of care will have greater success engaging HCV-affected Indigenous people who have used drugs into care.

Conclusion: There are several pragmatic ways to integrate Truth and Reconciliation as well as Indigenous concepts of whole-person wellness into the HCV cascade of care. By doing so, HCV treatment providers have an opportunity to create greater equity and support long-term wellness of Indigenous patients.},
keywords = {HCV treatment, Health equity, Indigenous peoples, Wellness},
pubstate = {published},
tppubtype = {article}
}

@article{A2019,
title = {Liver-related Events in Human Immunodeficiency Virus-infected Persons With Occult Cirrhosis},
author = {Benmassaoud A and Nitulescu R and Pembroke T and Halme AS and Ghali P and Deschenes M and Wong P and Klein MB and Sebastiani G},
url = {https://pubmed.ncbi.nlm.nih.gov/30561558/},
doi = {10.1093/cid/ciy1082},
year = {2019},
date = {2019-09-27},
journal = {Clinical Infectious Diseases},
abstract = {Background: Human immunodeficiency virus (HIV)-infected patients are at increased risk of liver-related mortality. The effect of occult cirrhosis (OcC), defined as preclinical compensated cirrhosis without any clinical findings, on liver-related events is unknown.

Methods: HIV-infected patients from 2 Canadian cohorts underwent transient elastography (TE) examination and were classified as (1) OcC (TE ≥13 kPa with no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (2) overt cirrhosis (OvC) (TE ≥13 kPa with signs of cirrhosis); or (3) noncirrhotic patients (TE <13 kPa). Incidence and risk factors of liver-related events were investigated through Kaplan-Meier and Cox regression analyses, respectively. We estimated monitoring rates according to screening guidelines for hepatocellular carcinoma (HCC) by OcC and OvC status.

Results: A total of 1092 HIV-infected patients (51% coinfected with hepatitis C virus) were included. Prevalence of OcC and OvC at baseline was 2.7% and 10.7%, respectively. During a median follow-up of 1.8 (interquartile range, 1.5-2.8) years, the incidence of liver-related events in noncirrhosis, OcC, and OvC was 3.4 (95% confidence interval [CI], 1.2-7.3), 34.0 (95% CI, 6.0-104.0), and 37.0 (95% CI, 17.0-69.1) per 1000 person-years, respectively. Baseline OcC (adjusted hazard ratio [aHR], 7.1 [95% CI, 1.3-38.0]) and OvC (aHR, 8.5 [95% CI, 2.8-26.0]) were independently associated with liver-related events. Monitoring rates for HCC were lower in patients with OcC (24%) compared to those with OvC (40%).

Conclusions: HIV-infected patients with OcC have a high incidence of liver-related events. Greater surveillance and earlier recognition with appropriate screening strategies are necessary for improved outcomes.},
keywords = {HCC surveilance, HIV, Liver-related events, Occult cirrhosis, Transient elastography},
pubstate = {published},
tppubtype = {article}
}

@article{RP2019,
title = {Evaluating Flexible Modeling of Continuous Covariates in Inverse-Weighted Estimators},
author = {Kyle RP and Moodie EEM and Klein MB and Abrahamowicz M},
url = {https://pubmed.ncbi.nlm.nih.gov/30649165/},
doi = {10.1093/aje/kwz004},
year = {2019},
date = {2019-06-01},
journal = {American Journal of Epidemiology},
abstract = {Correct specification of the exposure model is essential for unbiased estimation in marginal structural models with inverse-probability-of-treatment weights. However, although flexible modeling is commonplace when estimating effects of continuous covariates in outcome models, its use is less frequent in estimation of inverse probability weights. Using simulations, we assess the accuracy of the treatment effect estimates and covariate balance obtained with different exposure model specifications when the true relationship between a continuous, possibly time-varying covariate Lt and the logit of the probability of exposure is nonlinear. Specifically, we compare 4 approaches to modeling the effect of Lt when estimating inverse probability weights: a linear function, the covariate-balancing propensity score, and 2 easy-to-implement flexible methods that relax the assumption of linearity: cubic regression splines and fractional polynomials. Using data from 2 empirical studies, we compare linear exposure models with flexible exposure models to estimate the effect of sustained virological response to hepatitis C virus treatment on the progression of liver fibrosis. Our simulation results demonstrate that ignoring important nonlinear relationships when fitting the exposure model may provide poorer covariate balance and induce substantial bias in the estimated exposure-outcome associations. Analysts should routinely consider flexible modeling of continuous covariates when estimating inverse-probability-of-treatment weights.},
keywords = {Causal inference, Fractional polynomials, Marginal structural models, Model misspecification, Splines},
pubstate = {published},
tppubtype = {article}
}

@article{N2019,
title = {Trends in cause-specific mortality in HIV-hepatitis C coinfection following hepatitis C treatment scale-up},
author = {Kronfli N and Bhatnager SR and Hull M and Moodie E and Cooper C and Pick N and Walmsley S and Vachon ML and Martel-Leferriere V and Gill J and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/30946155/},
doi = {10.1097/QAD.0000000000002156},
year = {2019},
date = {2019-05-01},
journal = {AIDS},
abstract = {Objective: Hepatitis C virus (HCV) treatment may reduce liver-related mortality but with competing risks, other causes of mortality may undermine benefits. We examined changes in cause-specific mortality among HIV-HCV coinfected patients before and after scale-up of HCV treatment.

Design: Prospective multicentre HIV-HCV cohort study in Canada.

Methods: Cause-specific deaths, classified using a modified 'Coding of Cause of Death in HIV' protocol, were determined for two time periods, 2003-2012 and 2013-2017, stratified by age (20-49; 50-80 years). Comparison of trends between periods was performed using Poisson regression. To account for competing risks, multinomial regression was used to estimate the cause-specific hazard ratios of time and age on cause of death, from which end-stage liver disease (ESLD)-specific 5-year cumulative incidence functions were estimated.

Results: Overall, 1634 participants contributed 8248 person-years of follow-up; 273 (17%) died. Drug overdose was the most common cause of death overall, followed by ESLD and smoking-related deaths. In 2013-2017, ESLD was surpassed by drug overdose and smoking-related deaths among those aged 20-49 and 50-80, respectively. After accounting for competing risks, comparing 2003-2012 to 2013-2017, ESLD deaths declined (adjusted hazards ratio: 0.18, 95% confidence interval 0.05-0.62). However, both early and late period cumulative incidence functions demonstrated increased risk of death from ESLD for patients with poor HIV control and advanced fibrosis.

Conclusion: The gains made in overall mortality with HCV therapy may be thwarted if modifiable harms are not addressed. Although ESLD-related deaths have decreased over time, treatment should be further expanded, prioritizing those with advanced fibrosis.},
keywords = {Hepatitis C treatment, HIV-HCV co-infection, Mortality},
pubstate = {published},
tppubtype = {article}
}

@article{S2019,
title = {Evaluating the impact of health policies: using a difference-in-differences approach},
author = {Saeed S and Moodie EEM and Strumpf EC and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/30607473/},
doi = {10.1007/s00038-018-1195-2},
year = {2019},
date = {2019-05-01},
journal = {International Journal of Public Health},
keywords = {Health policies},
pubstate = {published},
tppubtype = {article}
}