2023 |
Jim Young Shouao Wang, Charlotte Lanièce Delaunay Curtis Cooper Joseph Cox John Gill Mark Hull Sharon Walmsley Alexander Wong Marina Klein; Canadian Coinfection Cohort Investigators L M B The rate of hepatitis C reinfection in Canadians coinfected with HIV and its implications for national elimination Journal Article Int J Drug Policy , 114 (103981), pp. 103981, 2023. Abstract | Links | BibTeX | Tags: 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 @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} } 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. |
2022 |
G Marathe; EEM, Moodie; MJ Brouillette; Cox; Cooper; Lanièce Delaunay; Conway; Hull; Martel-Laferrière; ML Vachon; Walmsley; Wong; MB Klein; J C C B M V S A; investigators., Canadian Co-Infection Cohort Predicting the presence of depressive symptoms in the HIV-HCV co-infected population in Canada using supervised machine learning. Journal Article BMC Medical Research Methodology, 2022. Abstract | Links | BibTeX | Tags: HIV, HIV-HCV co-infection @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} } 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. |
G Marathe; EEM, Moodie; MJ Brouillette; Lanièce Delaunay; Cox; Martel-Laferrière; Gill; Cooper; Pick; ML Vachon Walmsley; MB Klein; C J V J C N S; for the Investigators., Canadian Co-Infection Cohort Impact of HCV cure on depressive symptoms in the HIV-HCV co-infected population in Canada Journal Article Clinical Infectious Diseases, 2022. Abstract | Links | BibTeX | Tags: Depressive symptoms, Direct Acting Antivirals, HCV cure, HIV-HCV co-infection, Sustained virologic response @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} } 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. |
D Ortiz-Paredes; A, Amoako; Ekmekjian; Engler; Lebouché; MB Klein; T K B Interventions to improve uptake of direct-acting antivirals for hepatitis C virus in priority populations: A systematic review Journal Article Frontiers in Public Health, 2022. Abstract | Links | BibTeX | Tags: antiviral agents, hepatitis C, Indigenous peoples, People who inject drugs, sexual and gender minorities @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} } 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. |
C Laniece Delaunay; M, Maheu-Giroux; Marathe; Saeed Martel-Laferriere; Cooper; Walmsley; Cox; Wong MB Klein; G S S; V C S J A A; Gaps in hepatitis C virus prevention and care for HIV-hepatitis C virus co-infected people who inject drugs in Canada Journal Article International Journal of Drug Policy, 2022. Abstract | Links | BibTeX | Tags: drug injecting patterns, harm reduction, HCV Elimination, HCV treatment, HIV-HCV coinfection, People who inject drugs @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} } 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. |
G Marathe; EEM Moodie; MJ, Brouillette; Cox; Laniece Delaunay; Cooper Hull; Gill; Walmsley; Pick; MB Klein; J C C M J S N; investigators., Canadian Coinfection Cohort Depressive symptoms are no longer a barrier to HCV treatment initiation in the direct acting antiviral era Journal Article Antiviral Therapy, 2022. Abstract | Links | BibTeX | Tags: HIV, HIV-HCV co-infection @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} } 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. |
D Rodriguez Duque; D, Stephens; EEM Moodie; MB Klein; Semiparametric Bayesian inference for optimal dynamic treatment regimes via dynamic marginal structural models Journal Article Biostatistics, 2022. Abstract | Links | BibTeX | Tags: Bayesian inference, Dynamic treatment regimes, Marginal structural models @article{D2022, title = {Semiparametric Bayesian inference for optimal dynamic treatment regimes via dynamic marginal structural models}, author = {D, Rodriguez Duque; D, Stephens; EEM, Moodie; MB, Klein;}, url = {https://academic.oup.com/biostatistics/advance-article-abstract/doi/10.1093/biostatistics/kxac007/6564195?redirectedFrom=fulltext&login=false}, doi = {10.1093/biostatistics/kxac007}, year = {2022}, date = {2022-01-01}, journal = {Biostatistics}, abstract = {Considerable statistical work done on dynamic treatment regimes (DTRs) is in the frequentist paradigm, but Bayesian methods may have much to offer in this setting as they allow for the appropriate representation and propagation of uncertainty, including at the individual level. In this work, we extend the use of recently developed Bayesian methods for Marginal Structural Models to arrive at inference of DTRs. We do this (i) by linking the observational world with a world in which all patients are randomized to a DTR, thereby allowing for causal inference and then (ii) by maximizing a posterior predictive utility, where the posterior distribution has been obtained from nonparametric prior assumptions on the observational world data-generating process. Our approach relies on Bayesian semiparametric inference, where inference about a finite-dimensional parameter is made all while working within an infinite-dimensional space of distributions. We further study Bayesian inference of DTRs in the double robust setting by using posterior predictive inference and the nonparametric Bayesian bootstrap. The proposed methods allow for uncertainty quantification at the individual level, thereby enabling personalized decision-making. We examine the performance of these methods via simulation and demonstrate their utility by exploring whether to adapt HIV therapy to a measure of patients' liver health, in order to minimize liver scarring.}, keywords = {Bayesian inference, Dynamic treatment regimes, Marginal structural models}, pubstate = {published}, tppubtype = {article} } Considerable statistical work done on dynamic treatment regimes (DTRs) is in the frequentist paradigm, but Bayesian methods may have much to offer in this setting as they allow for the appropriate representation and propagation of uncertainty, including at the individual level. In this work, we extend the use of recently developed Bayesian methods for Marginal Structural Models to arrive at inference of DTRs. We do this (i) by linking the observational world with a world in which all patients are randomized to a DTR, thereby allowing for causal inference and then (ii) by maximizing a posterior predictive utility, where the posterior distribution has been obtained from nonparametric prior assumptions on the observational world data-generating process. Our approach relies on Bayesian semiparametric inference, where inference about a finite-dimensional parameter is made all while working within an infinite-dimensional space of distributions. We further study Bayesian inference of DTRs in the double robust setting by using posterior predictive inference and the nonparametric Bayesian bootstrap. The proposed methods allow for uncertainty quantification at the individual level, thereby enabling personalized decision-making. We examine the performance of these methods via simulation and demonstrate their utility by exploring whether to adapt HIV therapy to a measure of patients' liver health, in order to minimize liver scarring. |
2021 |
D Ortiz-Paredes; A, Amoako; Lessard; Engler; Lebouché; Klein; D K B M Canadian Liver Journal, 2021. Abstract | Links | BibTeX | Tags: direct-acting antivirals uptake, hepatitis C, men who have sex with men, MSM, People who inject drugs @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} } 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. |
D Ortiz-Paredes; A, Amoako; Lessard; Engler; Lebouché; Klein; D K B M Canadian Liver Journal, 2021. Abstract | Links | BibTeX | Tags: Direct-acting antivirals, hepatitis C, HIV infection, Indigenous peoples, men who have sex with men, People who inject drugs, Treatment uptake, Women @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} } 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. |
A Amoako; D, Ortiz-Paredes; Engler; Lebouché; MB Klein; K B International Journal of Drug Policy, 2021. Abstract | Links | BibTeX | Tags: Direct-acting antivirals; Hepatitis C; Indigenous; People who inject drugs; Qualitative; Systematic review. @article{A2021b, title = {Patient and Provider Perceived Barriers and Facilitators to Direct Acting Antiviral Hepatitis C Treatment Among Priority Populations in High Income Countries: A Knowledge Synthesis.}, author = {A, Amoako; D, Ortiz-Paredes; K, Engler; B, Lebouché; MB, Klein; }, url = {https://www.sciencedirect.com/science/article/pii/S0955395921001523?via%3Dihub}, doi = {10.1016/j.drugpo.2021.103247}, year = {2021}, date = {2021-10-02}, journal = {International Journal of Drug Policy}, abstract = {Background: Direct acting antivirals (DAAs) have increased cure rates for hepatitis C virus (HCV) infection; however, there are several obstacles to the uptake of DAAs in populations where substance use contributes to HCV risk. This synthesis aimed to identify the patient and provider perceived barriers and facilitators to DAA treatment initiation in key patient subgroups-people who inject drugs (PWID), men who have sex with men (MSM), and Indigenous people. Methods: We systematically searched seven databases and conducted a gray literature search for studies that qualitatively explored patient and provider perceived barriers and facilitators to DAA treatment in our populations of interest. Selected studies were published after 2013 when second generation DAAs became available. The titles, abstracts, and subsequently full texts were screened by two independent reviewers and critically appraised. Barriers and facilitators to DAA treatment uptake were then extracted and thematically synthesized. Results: 2144 titles and abstracts were identified and screened; 29 full texts were subsequently reviewed. Twelve qualitative studies were finally included. Among providers, perceived barriers to DAA treatment uptake included lack of resources and lack of provider knowledge on HCV while facilitators to treatment provision included simplicity of DAA regimens and professional identity as a doctor to advocate for patients. Among patients, perceived barriers to treatment uptake included current drug use, concerns about side effects of DAAs, stigma, gaps in community care, competing social responsibilities and mental health issues while facilitators included having a trustworthy provider and access to multidisciplinary HCV care. Conclusion: Despite simplicity of DAAs, many structural barriers to optimal HCV care continue to be experienced by patients and providers. In highlighting nuanced patient and provider perceived barriers and facilitators, this review underscores the need to involve participatory methods in the design and evaluation of interventions to best improve access to care.}, keywords = {Direct-acting antivirals; Hepatitis C; Indigenous; People who inject drugs; Qualitative; Systematic review.}, pubstate = {published}, tppubtype = {article} } Background: Direct acting antivirals (DAAs) have increased cure rates for hepatitis C virus (HCV) infection; however, there are several obstacles to the uptake of DAAs in populations where substance use contributes to HCV risk. This synthesis aimed to identify the patient and provider perceived barriers and facilitators to DAA treatment initiation in key patient subgroups-people who inject drugs (PWID), men who have sex with men (MSM), and Indigenous people. Methods: We systematically searched seven databases and conducted a gray literature search for studies that qualitatively explored patient and provider perceived barriers and facilitators to DAA treatment in our populations of interest. Selected studies were published after 2013 when second generation DAAs became available. The titles, abstracts, and subsequently full texts were screened by two independent reviewers and critically appraised. Barriers and facilitators to DAA treatment uptake were then extracted and thematically synthesized. Results: 2144 titles and abstracts were identified and screened; 29 full texts were subsequently reviewed. Twelve qualitative studies were finally included. Among providers, perceived barriers to DAA treatment uptake included lack of resources and lack of provider knowledge on HCV while facilitators to treatment provision included simplicity of DAA regimens and professional identity as a doctor to advocate for patients. Among patients, perceived barriers to treatment uptake included current drug use, concerns about side effects of DAAs, stigma, gaps in community care, competing social responsibilities and mental health issues while facilitators included having a trustworthy provider and access to multidisciplinary HCV care. Conclusion: Despite simplicity of DAAs, many structural barriers to optimal HCV care continue to be experienced by patients and providers. In highlighting nuanced patient and provider perceived barriers and facilitators, this review underscores the need to involve participatory methods in the design and evaluation of interventions to best improve access to care. |
N Kronfli; J, Young; Wang; Cox; Walmsley; Hull; Cooper; Martel-Laferriere; Wong; Pick; MB Klein; Canadian Coinfection Cohort Study Investigators. S J S M C V A N Clinical Infectious Diseases, 2021. Abstract | Links | BibTeX | Tags: APRI, Fibrosis regression, HIV-HCV coinfection, Sustained virologic response, Transient elastography @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} } 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. |
A Palayew; AM, Schmidt; Saeed; CL Cooper; Wong; Martel-Laferrière; Walmsley; Cox; MB Klein; S A V S J Estimating an individual-level deprivation index for HIV/HCV coinfected persons in Canada Journal Article PLOS One, 2021. Abstract | Links | BibTeX | Tags: Hepatitis C virus, HIV, HIV-HCV co-infection, Injection drug use, People who inject drugs @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} } 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. |
2020 |
S, Saeed; E, Strumpf; EEM, Moodie; L, Wong; J, Cox; S, Walmsley; M, Tyndall; C, Cooper; B, Conway; M, Hull; V, Martel-Laferriere; MJ, Gill; A, Wong; ML, Vachon; MB, Klein; for the Investigators, Canadian Co-Infection Cohort Study Clinical Infectious Diseases, 2020. Abstract | Links | BibTeX | Tags: Direct acting antivirals (DAAs), HIV-HCV co-infection, People who inject drugs, Quasi-experimental methods, Unrestricted access @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} } 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. |
W, Aibibula; J, Cox; AM, Hamelin; MB, Klein; P, Brassard AIDS and Behaviour, 2020. Abstract | Links | BibTeX | Tags: CD4 count, Food insecurity, HIV viral load, HIV-HCV co-infection, Mediation analysis @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} } 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. |
Kronfli, Nadine; Young, Jim; Wang, Shouao; Cox, Joseph; Walmsley, Sharon; Hull, Mark; Cooper, Curtis; Martel-Laferriere, Valerie; Wong, Alexander; Pick, Neora; Klein, Marina B; Investigators, Canadian Co-infection Cohort Study Clinical Infectious Diseases, 2020. Abstract | Links | BibTeX | Tags: APRI, Fibrosis regression, HIV-HCV co-infection, Sustained virologic response, Transient elastography @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} } 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. |
2019 |
ME, Pearce; K, Jongbloed; L, Demeras; H, MacDonald; WM, Christian; R, Sharma; N, Pick; EM, Yoshida; PM, Spittal; MB, Klein "Another thing to live for": Supporting HCV treatment and cure among Indigenous people impacted by substance use in Canadian cities Journal Article The International Journal on Drug Policy, 2019. Abstract | Links | BibTeX | Tags: HCV treatment, Health equity, Indigenous peoples, Wellness @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} } 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. |
A, Benmassaoud; R, Nitulescu; T, Pembroke; AS, Halme; P, Ghali; M, Deschenes; P, Wong; MB, Klein; G, Sebastiani Liver-related Events in Human Immunodeficiency Virus-infected Persons With Occult Cirrhosis Journal Article Clinical Infectious Diseases, 2019. Abstract | Links | BibTeX | Tags: HCC surveilance, HIV, Liver-related events, Occult cirrhosis, Transient elastography @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} } 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. |
RP, Kyle; EEM, Moodie; MB, Klein; M, Abrahamowicz Evaluating Flexible Modeling of Continuous Covariates in Inverse-Weighted Estimators Journal Article American Journal of Epidemiology, 2019. Abstract | Links | BibTeX | Tags: Causal inference, Fractional polynomials, Marginal structural models, Model misspecification, Splines @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} } 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. |
N, Kronfli; SR, Bhatnager; M, Hull; E, Moodie; C, Cooper; N, Pick; S, Walmsley; ML, Vachon; V, Martel-Leferriere; J, Gill; MB, Klein Trends in cause-specific mortality in HIV-hepatitis C coinfection following hepatitis C treatment scale-up Journal Article AIDS, 2019. Abstract | Links | BibTeX | Tags: Hepatitis C treatment, HIV-HCV co-infection, Mortality @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} } 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. |
S, Saeed; EEM, Moodie; EC, Strumpf; MB, Klein Evaluating the impact of health policies: using a difference-in-differences approach Journal Article International Journal of Public Health, 2019. Links | BibTeX | Tags: Health policies @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} } |