Documents de recherche

@article{G2022,
title = {Predicting the presence of depressive symptoms in the HIV-HCV co-infected population in Canada using supervised machine learning.},
author = {G, Marathe; EEM, Moodie; MJ, Brouillette; J, Cox; C, Cooper; C, Lanièce Delaunay; B, Conway; M, Hull; V, Martel-Laferrière; ML, Vachon; S, Walmsley; A, Wong; MB, Klein; and Canadian Co-Infection Cohort investigators.},
url = {https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-022-01700-y},
doi = {10.1186/s12874-022-01700-y},
year = {2022},
date = {2022-08-12},
journal = {BMC Medical Research Methodology},
abstract = {Background
Depression is common in the human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected population. Demographic, behavioural, and clinical data collected in research settings may be of help in identifying those at risk for clinical depression. We aimed to predict the presence of depressive symptoms indicative of a risk of depression and identify important classification predictors using supervised machine learning.

Methods
We used data from the Canadian Co-infection Cohort, a multicentre prospective cohort, and its associated sub-study on Food Security (FS). The Center for Epidemiologic Studies Depression Scale-10 (CES-D-10) was administered in the FS sub-study; participants were classified as being at risk for clinical depression if scores ≥ 10. We developed two random forest algorithms using the training data (80%) and tenfold cross validation to predict the CES-D-10 classes—1. Full algorithm with all candidate predictors (137 predictors) and 2. Reduced algorithm using a subset of predictors based on expert opinion (46 predictors). We evaluated the algorithm performances in the testing data using area under the receiver operating characteristic curves (AUC) and generated predictor importance plots.

Results
We included 1,934 FS sub-study visits from 717 participants who were predominantly male (73%), white (76%), unemployed (73%), and high school educated (52%). At the first visit, median age was 49 years (IQR:43–54) and 53% reported presence of depressive symptoms with CES-D-10 scores ≥ 10. The full algorithm had an AUC of 0.82 (95% CI:0.78–0.86) and the reduced algorithm of 0.76 (95% CI:0.71–0.81). Employment, HIV clinical stage, revenue source, body mass index, and education were the five most important predictors.

Conclusion
We developed a prediction algorithm that could be instrumental in identifying individuals at risk for depression in the HIV-HCV co-infected population in research settings. Development of such machine learning algorithms using research data with rich predictor information can be useful for retrospective analyses of unanswered questions regarding impact of depressive symptoms on clinical and patient-centred outcomes among vulnerable populations.},
keywords = {HIV, HIV-HCV co-infection},
pubstate = {published},
tppubtype = {article}
}

@article{G2022b,
title = {Impact of HCV cure on depressive symptoms in the HIV-HCV co-infected population in Canada},
author = {G, Marathe; EEM, Moodie; MJ, Brouillette; C, Lanièce Delaunay; J, Cox; V, Martel-Laferrière; J, Gill; C, Cooper; N, Pick; ML, Vachon, S, Walmsley; MB, Klein; and for the Canadian Co-Infection Cohort Investigators.},
url = {https://pubmed.ncbi.nlm.nih.gov/35789253/},
doi = {10.1093/cid/ciac540},
year = {2022},
date = {2022-08-01},
journal = {Clinical Infectious Diseases},
abstract = {Background: Depression is common in people living with HIV-HCV, with biological and psychosocial mechanisms at play. Direct acting antivirals (DAA) result in high rates of sustained virologic response (SVR), with minimal side-effects. We assessed the impact of SVR on presence of depressive symptoms in the HIV-HCV co-infected population in Canada during the second-generation DAA era (2013-2020).

Methods: We used data from the Canadian Co-infection Cohort (CCC), a multicentre prospective cohort of people with a HIV and HCV co-infection, and its associated sub-study on food security. Since depression screening was performed only in the sub-study, we predicted Center for Epidemiologic Studies Depression Scale-10 classes in the CCC using a random forest classifier and corrected for misclassification. We included participants who achieved SVR and fit a segmented modified Poisson model using an interrupted time series design, adjusting for time-varying confounders.

Results: We included 470 participants; 58% had predicted depressive symptoms at baseline. The median follow-up was 2.4 years (IQR: 1.0-4.5.) pre-SVR and 1.4 years (IQR: 0.6-2.5) post-SVR. The pre-SVR trend suggested depressive symptoms changed little over time, with no immediate level change at SVR. However, post-SVR trends showed a reduction of 5% per year (risk ratio: 0.95 (95%CI: 0.94-0.96)) in the prevalence of depressive symptoms.

Conclusions: In the DAA era, predicted depressive symptoms declined over time following SVR. These improvements reflect possible changes in biological pathways and/or better general health. If such improvements in depression symptoms are durable, this provides an additional reason for treatment and early cure of HCV.},
keywords = {Depressive symptoms, Direct Acting Antivirals, HCV cure, HIV-HCV co-infection, Sustained virologic response},
pubstate = {published},
tppubtype = {article}
}

@article{EEM2022,
title = {Depressive symptoms are no longer a barrier to HCV treatment initiation in the direct acting antiviral era},
author = {G Marathe; EEM, Moodie; MJ, Brouillette; J, Cox; C, Laniece Delaunay; C, Cooper M, Hull; J, Gill; S, Walmsley; N, Pick; MB, Klein; and Canadian Coinfection Cohort investigators.},
url = {https://journals.sagepub.com/doi/10.1177/13596535211067610},
doi = {10.1177/13596535211067610},
year = {2022},
date = {2022-01-27},
journal = {Antiviral Therapy},
abstract = {Background
Psychiatric illness was a major barrier for HCV treatment during the Interferon (IFN) treatment era due to neuropsychiatric side effects. While direct acting antivirals (DAA) are better tolerated, patient-level barriers persist. We aimed to assess the effect of depressive symptoms on time to HCV treatment initiation among HIV–HCV co-infected persons during the IFN (2003–2011) and second-generation DAA (2013–2020) eras.
Methods
We used data from the Canadian Co-infection Cohort, a multicentre prospective cohort, and its associated sub-study on Food Security (FS). We predicted Center for Epidemiologic Studies Depression Scale-10 (CES-D-10) classes for depressive symptoms indicative of a depression risk using a random forest classifier and corrected for misclassification using predictive value-based record-level correction. We used marginal structural Cox proportional hazards models with inverse weighting for competing risks (death) to assess the effect of depressive symptoms on treatment initiation among HCV RNA-positive participants.
Results
We included 590 and 1127 participants in the IFN and DAA eras. The treatment initiation rate increased from 9 (95% confidence interval (CI): 7–10) to 21 (95% CI: 19–22) per 100 person-years from the IFN to DAA era. Treatment initiation was lower among those with depressive symptoms compared to those without in the IFN era (hazard ratio: 0.81 (95% CI: 0.69–0.95)) and was higher in the DAA era (1.19 (95% CI: 1.10–1.27)).
Conclusion
Depressive symptoms no longer appear to be a barrier to HCV treatment initiation in the co-infected population in the DAA era. The higher rate of treatment initiation in individuals with depressive symptoms suggests those previously unable to tolerate IFN are now accessing treatment.},
keywords = {HIV, HIV-HCV co-infection},
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{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{R2019,
title = {Variation in hepatitis C virus treatment uptake between Canadian centres in the era of direct-acting antivirals},
author = {Nitulescu R and Young J and Saeed S and Cooper C and Cox J and Martel-Laferriere V and Hull M and Walmsley S and Tyndall MW and Wong A and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/30594080/},
doi = {10.1016/j.drugpo.2018.08.012},
year = {2019},
date = {2019-03-01},
journal = {The International Journal on Drug Policy},
abstract = {Background: Patients co-infected with HIV and hepatitis C virus (HCV) are a priority target for HCV treatment. The simplicity and efficacy of direct-acting antivirals (DAA) should help overcome patient, provider, and structural barriers to scaling up treatment.

Methods: We estimated between-centre variation in DAA treatment uptake among 1734 patients enrolled at the 18 centres of the Canadian Co-Infection Cohort-a prospective cohort of adults co-infected with HIV and HCV. We then compared this variation to that observed during the interferon era. Time to treatment uptake was modeled using a Weibull time-to-event model adjusting for centre and patient characteristics thought to have an impact on treatment initiation in the DAA era.

Results: At the time of administrative censoring (December 31, 2016), 981 cohort participants were eligible for second-generation DAA therapy (HCV RNA positive after November 21, 2013) of whom 278 initiated DAAs (16 patients per 100 person-years). Patients with low monthly income, Indigenous ethnicity, recent injection drug use, HCV genotype 3, or unknown HCV genotype were less likely to start treatment. After adjusting for patient characteristics, the estimated between-centre variance (σ2) was 0.29 (95% credible interval [CrI]: 0.09-0.89), considerably lower than during the interferon era (σ2 = 0.87, 95% CrI: 0.49-1.5). This between-centre variance was further reduced by the addition of centre-level effects for jurisdiction (σ2 = 0.15, 95% CrI: 0.02-0.60).

Conclusion: Much of the variation in treatment uptake between centres can now be attributed to regional differences. This suggests that after the introduction of DAAs, treatment barriers have shifted towards prescribing and reimbursement restrictions based on liver fibrosis, which vary by jurisdiction. The removal of these restrictions, however, will need to be paired with strategies to overcome patient-level barriers, which continue to prevent marginalized people and active substance users from accessing treatment.},
keywords = {Direct acting antivirals (DAAs), Disparities, HIV-HCV co-infection, Treatment barriers, Treatment uptake},
pubstate = {published},
tppubtype = {article}
}

@article{C2019,
title = {Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV-Coinfected Patients in Clinical Care},
author = {Rossi C and Young J and Martel-Laferriere V and Walmsley S and Cooper C and Wong A and Gill MJ and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/30882016/},
doi = {10.1093/ofid/ofz055},
year = {2019},
date = {2019-02-13},
journal = {Open Forum Infectious Diseases},
abstract = {Background: There are limited data on the real-world effectiveness of direct-acting antiviral (DAA) treatment in patients coinfected with hepatitis C virus (HCV) and HIV-a population with complex challenges including ongoing substance use, cirrhosis, and other comorbidities. We assessed how patient characteristics and the appropriateness of HCV regimen selection according to guidelines affect treatment outcomes in coinfected patients.

Methods: We included all patients who initiated DAA treatment between November 2013 and July 2017 in the Canadian Co-Infection Cohort. Sustained virologic response (SVR) was defined as an undetectable HCV RNA measured between 10 and 18 weeks post-treatment. We defined treatment failure as virologic failure, relapse, or death without achieving SVR. Bayesian logistic regression was used to estimate the posterior odds ratios (ORs) associated with patient demographic, clinical, and treatment-related risk factors for treatment failure.

Results: Two hundred ninety-five patients initiated DAAs; 31% were treatment-experienced, 29% cirrhotic, and 80% HCV genotype 1. Overall, 92% achieved SVR (263 of 286, 9 unknown), with the highest rates in females (97%) and lowest in cirrhotics (88%) and high-frequency injection drug users (89%). Many patients (38%) were prescribed regimens that were outside current clinical guidelines. This did not appreciably increase the risk of treatment failure-particularly in patients with genotype 1 (prior odds ratio [OR], 1.5; 95% credible interval [CrI], 0.38-6.0; posterior OR, 1.0; 95% CrI, 0.40-2.5).

Conclusions: DAAs were more effective than anticipated in a diverse, real-world coinfected cohort, despite the use of off-label, less efficacious regimens. High-frequency injection drug use and cirrhosis were associated with an increased risk of failure.},
keywords = {Direct acting antivirals (DAAs), Hepatitis C virus, HIV-HCV co-infection, Treatment failure, Treatment guidelines},
pubstate = {published},
tppubtype = {article}
}