Research Papers

@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{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}
}

@article{S2018,
title = {Real-world impact of direct acting antiviral therapy on health-related quality of life in HIV/Hepatitis C co-infected individuals},
author = {Saeed S and Moodie EEM and Strumpf E and Gill MJ and Wong A and Cooper C and Walmsley S and Hull M and Martel-Laferrière V and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/30141236/},
doi = {10.1111/jvh.12985},
year = {2018},
date = {2018-12-01},
journal = {Journal of Viral Hepatitis},
abstract = {Clinical trial results of direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) have shown improvements in health-related quality of life (HR-QoL). However, the extent to which these results are broadly generalizable to real-world settings is unknown. We investigated the real-world impact of oral DAA therapy on HR-QoL among individuals coinfected with HIV/HCV. We used data from the Canadian HIV/HCV Co-Infection Cohort Study that prospectively follows 1795 participants from 18 centres. Since 2007, clinical, lifestyle, and HR-QoL data have been collected biannually through self-administered questionnaires and chart review. HR-QoL was measured using the EQ-5D instrument. Participants initiating oral DAAs, having at least one visit before treatment initiation and at least one visit after DAA treatment response was ascertained, were included. Successful treatment response was defined as a sustained viral response (SVR). Segmented multivariate linear mixed models were used to evaluate the impact of SVR on HR-QoL, controlling for pretreatment trends. 227 participants met our eligibility criteria, 93% of whom achieved SVR. Before treatment, the EQ-5D utility index decreased 0.6 percentage-point/y (95% CI, -0.9, -0.3) and health state was constant over time. The immediate effect of SVR resulted in an increase of 2.3-units (-0.1, 4.7) in patients' health state and 2.0 percentage-point increase (-0.2, 4.0) in utility index. Health state continued to increase post-SVR by 1.4 units/y (-0.9, 3.7), while utility trends post-SVR plateaued over the observation period. Overall using real-world data, we found modest improvements in HR-QoL following SVR, compared to previously published clinical trials.},
keywords = {Direct acting antivirals (DAAs), EQ-5D, Health-related QOL, Hepatitis C virus, HIV},
pubstate = {published},
tppubtype = {article}
}

@article{T2018b,
title = {Injection drug use, food insecurity, and HIV-HCV co-infection: a longitudinal cohort analysis},
author = {McLinden T and Moodie EEM and Harper S and Hamelin AM and Anema A and Aibibula W and Klein MB and Cox J},
url = {https://pubmed.ncbi.nlm.nih.gov/29716392/},
doi = {10.1080/09540121.2018.1465171},
year = {2018},
date = {2018-10-01},
journal = {AIDS Care},
abstract = {Injection drug use (IDU) and food insecurity (FI) are highly prevalent among individuals living with HIV-hepatitis C virus (HCV) co-infection. We quantified the association between IDU and FI among co-infected individuals using biannual data from the Canadian Co-infection Cohort (N = 608, 2012-2015). IDU (in the past six months) and IDU frequency (non-weekly/weekly in the past month) were self-reported. FI (in the past six months) and FI severity (marginal FI, moderate FI, and severe FI) were measured using the Household Food Security Survey Module. Generalized estimating equations were used to estimate risk ratios (RR) quantifying the associations between IDU, IDU frequency, and FI with Poisson regression. The associations between IDU, IDU frequency, and FI severity were quantified by relative-risk ratios (RRR) estimated with multinomial regression. At the first time-point in the analytical sample, 54% of participants experienced FI in the past six months, 31% engaged in IDU in the six months preceding the FI measure, and 24% injected drugs in the past month. After adjustment for confounding, IDU in the past six months (RR = 1.15, 95% confidence interval [CI] = 1.04-1.28) as well as non-weekly (RR = 1.15, 95% CI = 1.02-1.29) and weekly IDU (RR = 1.21, 95% CI = 1.07-1.37) in the past month are associated with FI. Weekly IDU in the past month is also strongly associated with severe FI (RRR = 2.68, 95% CI = 1.47-4.91). Our findings indicate that there is an association between IDU and FI, particularly weekly IDU and severe FI. This suggests that reductions in IDU may mitigate FI, especially severe FI, in this vulnerable subset of the HIV-positive population.},
keywords = {Food insecurity, Hepatitis C virus, HIV, Injection drug use},
pubstate = {published},
tppubtype = {article}
}

@article{C2018,
title = {Hepatitis C virus cure does not impact kidney function decline in HIV co-infected patients},
author = {Rossi C and Saeed S and Cox J and Vachon ML and Martel-Laferrière V and Walmsley SL and Cooper C and Gill MJ and Hull M and Moodie EEM and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/29369156/},
doi = {10.1097/QAD.0000000000001750},
year = {2018},
date = {2018-03-27},
journal = {AIDS},
abstract = {Objective: To examine the impact of sustained virologic response (SVR) and illicit (injection and noninjection) drug use on kidney function among hepatitis C virus (HCV) and HIV co-infected individuals.

Design: Longitudinal observational cohort study of HCV-HIV co-infected patients.

Methods: Data from 1631 patients enrolled in the Canadian Co-Infection Cohort between 2003 and 2016 were analyzed. Patients who achieved SVR were matched 1 : 2 with chronically infected patients using time-dependent propensity scores. Linear regression with generalized estimating equations was used to model differences in estimated glomerular filtration rates (eGFR) between chronic HCV-infected patients and those achieving SVR. The relationship between illicit drug use and eGFR was explored in patients who achieved SVR.

Results: We identified 384 co-infected patients who achieved SVR (53% treated with interferon-free antiviral regimens) and 768 propensity-score matched patients with chronic HCV infection. Most patients were men (78%) and white (87%), with a median age of 51 years (interquartile range: 45-56). During 1767 person-years of follow-up, 4041 eGFR measurements were available for analysis. Annual rates of decline in eGFR were similar between patients with SVR [-1.32 (ml/min per 1.73 m)/year, 95% confidence interval (CI) -1.75 to -0.90] and chronic infection [-1.19 (ml/min per 1.73 m) per year, 95% CI -1.55 to -0.84]. Among SVR patients, recent injection cocaine use was associated with rapid eGFR decline [-2.16 (ml/min per 1.73 m)/year, 95% CI -4.17 to -0.16].

Conclusion: SVR did not reduce the rate of kidney function decline among HCV-HIV co-infected patients. Increased risk of chronic kidney disease in co-infection may not be related to persistent HCV replication but to ongoing injection cocaine use.},
keywords = {Hepatitis C virus, Kidney function, Sustained virologic response},
pubstate = {published},
tppubtype = {article}
}

@article{T2018,
title = {Methadone treatment, severe food insecurity, and HIV-HCV co-infection: A propensity score matching analysis},
author = {McLinden T and Moodie EEM and Hamelin AM and Harper S and Rossi C and Walmsley SL and Rourke SB and Cooper C and Klein MB and Cox J},
url = {https://pubmed.ncbi.nlm.nih.gov/29544189/},
doi = {10.1016/j.drugalcdep.2017.12.031},
year = {2018},
date = {2018-02-20},
journal = {Drug and Alcohol Dependance},
abstract = {Background: Severe food insecurity (FI) is common among individuals living with HIV-hepatitis C virus (HCV) co-infection. We hypothesize that the injection of opioids is partly responsible for the association between injection drug use and severe FI. Therefore, this analysis examines whether methadone maintenance treatment for opioid dependence is associated with a lower risk of severe FI.

Methods: We used biannual data from the Canadian Co-infection Cohort (N = 608, 2012-2015). Methadone treatment (exposure) was self-reported and severe FI (outcome) was measured using the Household Food Security Survey Module. To quantify the association between methadone treatment and severe FI, we estimated an average treatment effect on the treated (marginal risk difference [RD]) using propensity score matching.

Results: Among participants, 25% experienced severe FI in the six months preceding the first time-point in the analytical sample and 5% concurrently reported receiving methadone treatment. Injection of opioids in the six months preceding the treatment and outcome measurements was much higher among those who received methadone treatment (39% vs. 12%). Among the treated participants, 97% had injected opioids in their lifetimes. After propensity score matching, the average risk of experiencing severe FI is 12.3 percentage-points lower among those receiving methadone treatment, compared to those who are not receiving treatment (marginal RD = -0.123, 95% CI = -0.230, -0.015).

Conclusions: After adjustment for socioeconomic, sociodemographic, behavioural, and clinical confounders, methadone treatment is associated with a lower risk of severe FI. This finding suggests that methadone treatment may mitigate severe FI in this vulnerable subset of the HIV-positive population.},
keywords = {Hepatitis C virus, HIV, Methadone treatment, Propensity score matching, Severe food insecurity},
pubstate = {published},
tppubtype = {article}
}

@article{T2017b,
title = {Injection Drug Use, Unemployment, and Severe Food Insecurity Among HIV-HCV Co-Infected Individuals: A Mediation Analysis},
author = {McLinden T and Moodie EEM and Hamelin AM and Harper S and Walmsley SL and Paradis G and Aibibula W and Klein MB and Cox J},
url = {https://pubmed.ncbi.nlm.nih.gov/28726043/},
doi = {10.1007/s10461-017-1850-2},
year = {2017},
date = {2017-12-01},
journal = {AIDS and Behaviour},
abstract = {Severe food insecurity (FI), which indicates reduced food intake, is common among HIV-hepatitis C virus (HCV) co-infected individuals. Given the importance of unemployment as a proximal risk factor for FI, this mediation analysis examines a potential mechanism through which injection drug use (IDU) is associated with severe FI. We used biannual data from the Canadian Co-infection Cohort (N = 429 with 3 study visits, 2012-2015). IDU in the past 6 months (exposure) and current unemployment (mediator) were self-reported. Severe FI in the following 6 months (outcome) was measured using the Household Food Security Survey Module. An overall association and a controlled direct effect were estimated using marginal structural models. Among participants, 32% engaged in IDU, 78% were unemployed, and 29% experienced severe FI. After adjustment for confounding and addressing censoring through weighting, the overall association (through all potential pathways) between IDU and severe FI was: risk ratio (RR) = 1.69 (95% confidence interval [CI] = 1.15-2.48). The controlled direct effect (the association through all potential pathways except that of unemployment) was: RR = 1.65 (95% CI = 1.08-2.53). We found evidence of an overall association between IDU and severe FI and estimated a controlled direct effect that is suggestive of pathways from IDU to severe FI that are not mediated by unemployment. Specifically, an overall association and a controlled direct effect that are similar in magnitude suggests that the potential impact of IDU on unemployment is not the primary mechanism through which IDU is associated with severe FI. Therefore, while further research is required to understand the mechanisms linking IDU and severe FI, the strong overall association suggests that reductions in IDU may mitigate severe FI in this vulnerable subset of the HIV-positive population.},
keywords = {Hepatitis C virus, HIV, Injection drug use, Severe food insecurity, Unemployment},
pubstate = {published},
tppubtype = {article}
}

@article{J2017,
title = {Risk Factors for Hepatitis C Virus Reinfection After Sustained Virologic Response in Patients Coinfected With HIV},
author = {Young J and Rossi C and Gill J and Walmsley S and Cooper C and Cox J and Martel-Laferriere V and Conway B and Pick N and Vachon ML and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/28199495/},
doi = {10.1093/cid/cix126},
year = {2017},
date = {2017-05-01},
journal = {Clinical Infectious Diseases},
abstract = {Background: Highly effective hepatitis C virus (HCV) therapies have spurred a scale-up of treatment to populations at greater risk of reinfection after sustained virologic response (SVR). Reinfection may be higher in HIV-HCV coinfection, but prior studies have considered small selected populations. We assessed risk factors for reinfection after SVR in a representative cohort of Canadian coinfected patients in clinical care.

Methods: All patients achieving SVR after HCV treatment were followed with HCV RNA measurements every 6 months in a prospective cohort study. We used Bayesian Cox regression to estimate reinfection rates according to patient reported injection drug use (IDU) and sexual activity among men who have sex with men (MSM).

Results: Of 497 patients treated for HCV, 257 achieved SVR and had at least 1 subsequent RNA measurement. During 589 person-years of follow-up (PYFU) after SVR, 18 (7%) became HCV RNA positive. The adjusted reinfection rate (per 1000 PYFU) in the first year after SVR was highest in those who reported high-frequency IDU (58; 95% credible interval [CrI], 18-134) followed by MSM reporting high-risk sexual activity (26; 95% CrI, 6-66) and low-frequency IDU (22; 95% CrI, 4-68). The rate in low-risk MSM (16; 95% CrI, 4-38) was similar to that in reference patients (10; 95% CrI, 4-20). Reinfection rates did not diminish with time.

Conclusions: HCV reinfection rates varied according to risk. Measures are needed to reduce risk behaviors and increase monitoring in high-risk IDU and MSM if HCV elimination targets are to be realized.},
keywords = {Hepatitis C treatment, Hepatitis C virus, HIV, Reinfection, Sustained virologic response},
pubstate = {published},
tppubtype = {article}
}