Research Papers

@article{Cox2017,
title = {Food Insecurity in HIV-Hepatitis C Virus Co-infected Individuals in Canada: The Importance of Co-morbidities},
author = {Joseph Cox and Anne-Marie Hamelin and Taylor McLinden and Erica E. M. Moodie and Aranka Anema and Kathleen C. Rollet-Kurhajec and Gilles Paradis and Sean B. Rourke and Sharon Walmsley and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26912217},
doi = {10.1007/s10461-016-1326-9},
year = {2017},
date = {2017-03-15},
journal = {AIDS and Behavior},
abstract = {While research has begun addressing food insecurity (FI) in HIV-positive populations, knowledge regarding FI among individuals living with HIV-hepatitis C virus (HCV) co-infection is limited. This exploratory study examines sociodemographic, socioeconomic, behavioral, and clinical factors associated with FI in a cohort of HIV-HCV co-infected individuals in Canada. We analyzed longitudinal data from the Food Security and HIV-HCV Co-infection Study of the Canadian Co-infection Cohort collected between November 2012-June 2014 at 15 health centres. FI was measured using the Household Food Security Survey Module and classified using Health Canada criteria. Generalized estimating equations were used to assess factors associated with FI. Among 525 participants, 59 % experienced FI at their first study visit (baseline). Protective factors associated with FI (p < 0.05) included: enrolment at a Quebec study site (aOR: 0.42, 95 % CI: 0.27, 0.67), employment (aOR: 0.55, 95 % CI: 0.35, 0.87), and average personal monthly income (aOR per $100 CAD increase: 0.98, 95 % CI: 0.97, 0.99). Risk factors for FI included: recent injection drug use (aOR: 1.98, 95 % CI: 1.33, 2.96), trading away food (aOR: 5.23, 95 % CI: 2.53, 10.81), and recent experiences of depressive symptoms (aOR: 2.11, 95 % CI: 1.48, 3.01). FI is common in this co-infected population. Engagement of co-infected individuals in substance use treatments, harm reduction programs, and mental health services may mitigate FI in this vulnerable subset of the HIV-positive population.},
keywords = {Canada, Co-infection, Food insecurity, HCV, HIV},
pubstate = {published},
tppubtype = {article}
}

@article{Klein2014,
title = {Mortality in HIV-Hepatitis C Co-infected patients enrolled in the Canadian Co-infection Cohort study compared to the general Canadian population (2003-2013)},
author = {Marina B. Klein and Kathleen C. Rollet-Kurhajec and Erica E. M. Moodie and Sean Yaphe and Mark Tyndall and Sharon Walmsley and John Gill and Valerie Martel-Laferriere and Curtis Cooper},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25259703},
doi = {10.1097/QAD.0000000000000377},
year = {2014},
date = {2014-08-24},
journal = {AIDS},
volume = {28},
number = {13},
pages = {1957-1965},
abstract = {OBJECTIVE:
Recent studies suggest all-cause mortality in HIV mono-infected patients approaches that of the general population. We aimed to compare participants in the Canadian Co-infection Cohort to the general population to determine if co-infected patients have had similar improvements in mortality.
DESIGN:
Prospective multicentre cohort study.
METHODS:
Between 2003 and 2013, deaths were captured using specific case reports and through linkage to provincial vital statistics for participants lost to follow-up. Standardized mortality ratios (SMRs) were calculated using age, sex and province-specific mortality rates from the Canadian Human Mortality Database, 2009, and compared across behavioural and clinical characteristics of participants at their most recent visit.
RESULTS:
Among the 1150 patients, we observed 133 deaths over 3351 person-years (4.0 per 100 person-years, 95% confidence interval 3.3, 4.6). SMRs (95% confidence interval) were: 12.1(10.1, 14.2) overall; 9.3 (7.5, 11.1) for men and 19.4 (12.7, 26.2) for women. CD4 cell counts below 200 cells/μl [25.5 (17.7, 33.3)], active injection drug use [19.9 (13.9, 25.9)] and smoking [14.9 (12.1, 17.7)] were strongly associated with excess mortality. Lowest SMRs were seen for those who had spontaneous [4.5 (-0.6, 9.5)] or treatment-induced clearance of hepatitis C virus (HCV) infection [5.1 (1.3, 8.8)]. Conversely, high SMRs were seen with advanced liver disease [17.0 (11.7, 22.3)]. In no category did SMRs approach mortality seen in the general Canadian population.
CONCLUSIONS:
HIV-HCV co-infected persons remain at markedly increased risk for death despite antiretroviral therapy. Interventions targeting modifiable risk factors such as substance use, smoking, adherence to antiretrovirals and timely provision of HCV therapy could substantially reduce death rates.},
keywords = {Canada, HIV-HCV co-infection, Mortality},
pubstate = {published},
tppubtype = {article}
}

@article{Young2013,
title = {Variation between Canadian centres in the uptake of treatment for Hepatitis C by patients co-infected with HIV},
author = {Jim Young and Martin Potter and Joseph Cox and Curtis Cooper and John Gill and Mark Hull and Sharon Walmsley and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985981/},
doi = {10.9778/cmajo.20130009},
year = {2013},
date = {2013-09-30},
journal = {CMAJ Open},
volume = {1},
number = {3},
pages = {106-114},
abstract = {Background: Uptake of treatment for Hepatitis C virus (HCV) is low in Canada despite its publicly funded health care system. We explored the uptake of HCV treatment within the Canadian Co-infection Cohort to determine if some treatment centres have been more successful than others at starting patients with HIV–HCV coinfection on HCV treatment.

Methods: We estimated the variation between 16 centres in the uptake of HCV treatment using a Weibull time-to-event model with adjustment for patient characteristics that are thought likely to influence the uptake of treatment. We asked the principal investigator at each centre about access to hepatitis-related specialists and services and the importance of various criteria when determining if a patient with HIV–HCV coinfection should receive treatment for HCV.

Results: Among 681 untreated patients in the Canadian Co-infection Cohort, 163 patients with HIV–HCV coinfection started HCV treatment over a period of 1827 patient-years (9 per 100 patient-years). Even after adjustment for case mix, there was still appreciable variation in treatment uptake between centres, with mean hazard ratios of 0.43 (95% credible interval 0.11–1.3) and 3.6 (95% credible interval 1.7–8.4) for the centres least and most likely to start an average patient with HIV–HCV coinfection on HCV treatment. The most important criteria reported by principal investigators for determining eligibility for treatment were severity of fibrosis, current psychiatric comorbidities, current alcohol intake, past HCV treatment and a history of reinfection with HCV. However, the opinions were wide-ranging: 8 of the 15 criteria elicited both the responses “less important” and “very important.”

Interpretation: The magnitude of the centre effects and diverse opinions about the importance of treatment eligibility criteria suggest that provider-related barriers to HCV treatment uptake are as important as patient-related barriers.},
keywords = {Canada, HCV, HIV-HCV co-infection, Variation},
pubstate = {published},
tppubtype = {article}
}

@article{Klein2013,
title = {HIV and Hepatitis C virus Co-infection in Canada: Challenges and Opportunities for Reducing Preventable Morbidity and Mortality},
author = {Marina B. Klein and Kathleen C. Rollet-Kurhajec and Sahar Saeed and Joseph Cox and Martin Potter and Jeff Cohen and Brian Conway and Curtis Cooper and Pierre Côté and John Gill and David Haase and Shariq Haider and Mark Hull and Erica E. M. Moodie and Julio Montaner and Neora Pick and Anita Rachlis and Danielle Rouleau and Roger Sandre and Mark Tyndall and Sharon Walmsley},
url = {https://www.ncbi.nlm.nih.gov/pubmed/22639840},
doi = {10.1111/j.1468-1293.2012.01028.x},
year = {2013},
date = {2013-01-15},
journal = {HIV Med},
volume = {14},
number = {1},
pages = {10-20},
abstract = {OBJECTIVES:
Hepatitis C virus (HCV) has emerged as an important health problem in the era of effective HIV treatment. However, very few data exist on the health status and disease burden of HIV/HCV-coinfected Canadians.
METHODS:
HIV/HCV-coinfected patients were enrolled prospectively in a multicentre cohort from 16 centres across Canada between 2003 and 2010 and followed every 6 months. We determined rates of a first liver fibrosis or endstage liver disease (ESLD) event and all-cause mortality since cohort enrolment and calculated standardized mortality ratios compared with the general Canadian population.
RESULTS:
A total of 955 participants were enrolled in the study and followed for a median of 1.4 (interquartile range 0.5-2.3) years. Most were male (73%) with a median age of 44.5 years; 13% self-identified as aboriginal. There were high levels of current injecting drug and alcohol use and poverty. Observed event rates [per 100 person-years; 95% confidence interval (CI)] were: significant fibrosis (10.21; 8.49, 12.19), ESLD (3.16; 2.32, 4.20) and death (3.72; 2.86, 4.77). The overall standardized mortality ratio was 17.08 (95% CI 12.83, 21.34); 12.80 (95% CI 9.10, 16.50) for male patients and 28.74 (95% CI 14.66, 42.83) for female patients. The primary causes of death were ESLD (29%) and overdose (24%).
CONCLUSIONS:
We observed excessive morbidity and mortality in this HIV/HCV-coinfected population in care. Over 50% of observed deaths may have been preventable. Interventions aimed at improving social circumstances, reducing harm from drug and alcohol use and increasing the delivery of HCV treatment in particular will be necessary to reduce adverse health outcomes among HIV/HCV-coinfected persons.
© 2012 British HIV Association.},
keywords = {Canada, HIV-HCV co-infection, Morbidity, Mortality},
pubstate = {published},
tppubtype = {article}
}

@article{Klein2009,
title = {Cohort Profile: The Canadian HIV-Hepatitis C Co-infection Cohort study},
author = {Marina B. Klein and Sahar Saeed and Hong Yang and Jeff Cohen and Brian Conway and Curtis Cooper and Pierre Côté and Joseph Cox and John Gill and David Haase and Shariq Haider and Julio Montaner and Neora Pick and Anita Rachlis and Danielle Rouleau and Roger Sandre and Mark Tyndall and Sharon Walmsley},
url = {https://www.ncbi.nlm.nih.gov/pubmed/19786463},
doi = {10.1093/ije/dyp297},
year = {2009},
date = {2009-09-28},
journal = {International Journal of Epidemiology},
volume = {39},
number = {5},
pages = {1162-1169},
abstract = {What is the Canadian HIV–Hepatitis C Co-infection Cohort and how did the study come about?

Hepatitis C virus (HCV) has emerged as one of the most vexing health problems facing HIV-infected persons. Due largely to injection drug use (IDU), >30% of HIV-infected patients are co-infected with HCV in developed countries1,2 with 10 million co-infected worldwide.3 In 1999, 11 194 Canadians were estimated to be co-infected4 and this number has likely increased substantially since. HCV infection has also increasingly been reported in HIV-positive men having sex with men (MSM) who have not used injection drugs.5 Since the advent of highly active antiretroviral therapy (HAART) there have been dramatic reductions in morbidity and mortality from virtually all causes of illness among HIV-infected persons.6,7 One of the glaring exceptions to this trend is death from end-stage liver disease (ESLD) with rates increasing 4- to 8-fold in the post-HAART era.8–11 This excess mortality may be due, in part, to improved overall survival associated with HAART, allowing competing morbidities and mortalities that were once rarely observed. In addition, HCV-associated hepatic fibrosis has been shown to progress more rapidly in the context of HIV infection,12–14 likely due to immune dysfunction.15–17 Several other factors may be at play, including chronic hepatotoxicity related to antiretrovirals, incomplete immune recovery, heavy alcohol use and problems with access and/or adherence to HAART and HCV treatment in a population with high rates of substance use. The growing burden of chronic HCV infection is expected to result in dramatic increases in the rates of cirrhosis, liver failure, hepatocellular carcinoma, transplant needs18 and related annual healthcare costs in Canada19 and worldwide.

Understanding the complex interplay between socio-demographic factors, substance use, biology and treatments that may affect outcomes in co-infection is necessary to meet the challenge of providing effective medical care to the growing number of HIV–HCV co-infected persons. The Canadian HIV–HCV co-infection cohort (CCC) brings together experts in HIV, infectious diseases, hepatology, immunology, public health, biostatistics and epidemiology in a translational research program that is aimed at addressing the multifaceted nature of co-infection.

In 2003 we launched a prospective pilot study in Quebec funded by the Fonds de la recherche en santé du Québec (FRSQ). Patients were identified from existing clinic populations at three university-based HIV clinics providing multidisciplinary team care located in Montreal, Quebec, Canada: during the pilot phase of this project we recruited 253 patients and followed them for 2 years. Data obtained were then used to estimate expected rates of exposures and outcomes for power calculations, as well as for planning and anticipating the logistics required to conduct a larger Canadian study. Furthermore, we clearly demonstrated the feasibility of maintaining a cohort study with a population of patients that is traditionally considered difficult to follow.},
keywords = {Canada, HCV, HIV, HIV-HCV co-infection},
pubstate = {published},
tppubtype = {article}
}