Research Papers

@article{Cox2014,
title = {Correlates of drug use cessation among participants in the Canadian HIV-HCV Co-infection Cohort},
author = {Joseph Cox and Emilie Maurais and Lina Hu and Erica E. M. Moodie and Stephanie Law and Nikki Bozinoff and Martin Potter and Kathleen C. Rollet-Kurhajec and Mark Hull and Mark Tyndall and Curtis Cooper and John Gill and Sahar Saeed and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24559606},
doi = {10.1016/j.drugalcdep.2014.01.014},
year = {2014},
date = {2014-04-15},
journal = {Drug and Alcohol Dependence},
volume = {137},
pages = {121-128},
abstract = {BACKGROUND:
Ongoing drug use remains a barrier to HIV and HCV treatment. We examined the occurrence and correlates of drug use cessation among HIV-HCV co-infected drug users participating in HIV care.
METHODS:
Participants from the Canadian Co-infection Cohort reporting drug use (injecting drugs and/or smoking crack) with at least two follow-up visits were included (n=521 (43%), 1832 visits). Socio-demographics, behavioural, and health information were collected at each six-month visit. Associations with cessation (no drug use since last visit) were examined using non-linear mixed effects logistic regression models with random intercepts.
RESULTS:
During follow-up, 361 (69%) participants ceased using drugs. Having a fixed address (aOR [adjusted odds ratio] 1.73, CI [95% confidence interval] 1.02-2.96) and smoking crack without injecting drugs (aOR 3.10, CI 2.05-4.71) were positively associated. Living alone (aOR 0.47, CI 0.35-0.63), current tobacco use (aOR 0.41, CI 0.26-0.64), hazardous alcohol drinking (aOR 0.67, CI 0.49-0.91), snorting drugs (aOR 0.52, CI 0.37-0.74), having a greater exposure to addiction programmes (aOR 0.88, CI 0.81-0.94), having been recruited in Quebec or Nova Scotia (aOR 0.41, CI 0.25-0.66), and British Columbia or Alberta (aOR 0.51, CI 0.32-0.82) were negatively associated. Various socio-demographic (age, education) and health-related (HIV duration, care adherence) factors were not associated.
CONCLUSION:
Drug use cessation among HIV-HCV co-infected persons is relatively common in this cohort. Stable housing and supportive living situations seem to be important facilitators for drug use cessation in this population. Greater efforts should be made to retain patients in addiction treatment programmes.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.},
keywords = {Crack cessation, Determinants of health, HIV-HCV co-infection, Injection drug use cessation},
pubstate = {published},
tppubtype = {article}
}

@article{Schnitzer2014,
title = {Modeling the impact of Hepatitis C viral clearance on End-stage liver disease in an HIV co-infected Cohort with targeted maximum likelihood estimation},
author = {Mireille E. Schnitzer and Erica E. M. Moodie and Mark J. van der Laan and Robert W. Platt and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954273/},
doi = {10.1111/biom.12105},
year = {2014},
date = {2014-03-14},
journal = {Biometrics},
volume = {70},
number = {1},
pages = {144-152},
abstract = {Despite modern effective HIV treatment, Hepatitis C virus (HCV) Co-infection is associated with a high risk of progression to End-stage liver disease (ESLD) which has emerged as the primary cause of death in this population. Clinical interest lies in determining the impact of clearance of HCV on risk for ESLD. In this case study, we examine whether HCV clearance affects risk of ESLD using data from the multicenter Canadian Co-infection Cohort study. Complications in this survival analysis arise from the time-dependent nature of the data, the presence of baseline confounders, loss to follow-up, and confounders that change over time, all of which can obscure the causal effect of interest. Additional challenges included non-censoring variable missingness and event sparsity. In order to efficiently estimate the ESLD-free survival probabilities under a specific history of HCV clearance, we demonstrate the double-robust and semiparametric efficient method of Targeted Maximum Likelihood Estimation (TMLE). Marginal structural models (MSM) can be used to model the effect of viral clearance (expressed as a hazard ratio) on ESLD-free survival and we demonstrate a way to estimate the parameters of a logistic model for the hazard function with TMLE. We show the theoretical derivation of the efficient influence curves for the parameters of two different MSMs and how they can be used to produce variance approximations for parameter estimates. Finally, the data analysis evaluating the impact of HCV on ESLD was undertaken using multiple imputations to account for the non-monotone missing data.},
keywords = {Double-robust, Inverse probability weighting, Kaplan-Meier, Longitudinal data, Marginal structural models, Survival analysis, Targeted maximum likelihood estimation},
pubstate = {published},
tppubtype = {article}
}

@article{Beauchamp2013,
title = {Missed opportunities for hepatocellular carcinoma screening in an HIV-Hepatitis C virus co-infected Cohort},
author = {Elizabeth Beauchamp and Kathleen C. Rollet-Kurhajec and Sharon Walmsley and David K. Wong and Curtis Cooper and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23899675},
doi = {10.1093/cid/cit491},
year = {2013},
date = {2013-11-15},
journal = {Clinical Infectious Diseases},
volume = {57},
number = {9},
pages = {1339-1342},
abstract = {We examined adherence to guidelines for screening of hepatocellular carcinoma in a cohort of HIV/hepatitis C virus-coinfected patients. Thirty-six percent of patients with documented cirrhosis did not have a screening ultrasound. Patients at centers with standardized systems for screening were more likely to have had an ultrasound performed.},
keywords = {Carcinoma, HCV, HIV},
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{Brunet2013,
title = {Marijuana Smoking Does Not Accelerate Progression of Liver Disease in HIV–Hepatitis C Coinfection: A Longitudinal Cohort Analysis},
author = {Laurence Brunet and Erica E. M. Moodie and Kathleen C. Rollet-Kurhajec and Curtis Cooper and Sharon Walmsley and Martin Potter and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23811492},
doi = {10.1093/cid/cit378},
year = {2013},
date = {2013-09-14},
journal = {Clinical Infectious Diseases},
volume = {57},
number = {5},
pages = {663-670},
abstract = {BACKGROUND:
Marijuana smoking is common and believed to relieve many symptoms, but daily use has been associated with liver fibrosis in cross-sectional studies. We aimed to estimate the effect of marijuana smoking on liver disease progression in a Canadian prospective multicenter cohort of human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected persons.
METHODS:
Data were analyzed for 690 HCV polymerase chain reaction positive (PCR-positive) individuals without significant fibrosis or end-stage liver disease (ESLD) at baseline. Time-updated Cox Proportional Hazards models were used to assess the association between the average number of joints smoked/week and progression to significant liver fibrosis (APRI ≥ 1.5), cirrhosis (APRI ≥ 2) or ESLD.
RESULTS:
At baseline, 53% had smoked marijuana in the past 6 months, consuming a median of 7 joints/week (IQR, 1-21); 40% smoked daily. There was no evidence that marijuana smoking accelerates progression to significant liver fibrosis (APRI ≥ 1.5) or cirrhosis (APRI ≥ 2; hazard ratio [HR]: 1.02 [0.93-1.12] and 0.99 [0.88-1.12], respectively). Each 10 additional joints/week smoked slightly increased the risk of progression to a clinical diagnosis of cirrhosis and ESLD combined (HR, 1.13 [1.01-1.28]). However, when exposure was lagged to 6-12 months before the diagnosis, marijuana was no longer associated with clinical disease progression (HR, 1.10 [0.95-1.26]).
CONCLUSIONS:
In this prospective analysis we found no evidence for an association between marijuana smoking and significant liver fibrosis progression in HIV/HCV coinfection. A slight increase in the hazard of cirrhosis and ESLD with higher intensity of marijuana smoking was attenuated after lagging marijuana exposure, suggesting that reverse causation due to self-medication could explain previous results.},
keywords = {Cannabis, Cohort study, HCV, HIV, Liver disease},
pubstate = {published},
tppubtype = {article}
}

@article{MW2013,
title = {Reply to Mandorfer et al},
author = {Hull MW and Rollet K and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/23243174/},
doi = {10.1093/cid/cis1036},
year = {2013},
date = {2013-03-01},
journal = {Clinical Infectious Diseases},
keywords = {HIV-HCV co-infection},
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{Klein2012,
title = {Who needs direct acting antivirals for Hepatitis C Virus (HCV)? Challenges faced in advancing HCV therapy for HIV-HCV co-infected persons},
author = {Marina B. Klein and Kathleen C. Rollet-Kurhajec and Mark Hull and Curtis Cooper and Sharon Walmsley and Brian Conway and Neora Pick},
url = {https://www.intmedpress.com/journals/avt/abstract.cfm?id=2484&pid=88},
doi = {10.3851/IMP2484},
year = {2012},
date = {2012-12-04},
journal = {Antiviral Therapy},
volume = {18},
pages = {717-721},
abstract = {Background: The recent availability of new direct-acting antivirals (DAAs) for HCV treatment, which significantly increase sustained virological response rates for genotype 1 HCV infection, has brought new optimism with respect to curative HCV treatment for HIV–HCV-coinfected patients. We describe the characteristics of coinfected patients who could be eligible for DAAs to determine potential challenges facing clinicians and patients hoping to take advantage of these new therapies.

Methods: We evaluated the sociodemographic and clinical characteristics of the genotype 1 HCV–HIV-infected participants in a Canadian prospective multicentre cohort study at their most recent visit to assess potential eligibility for combination HCV treatment with boceprevir or telaprevir.

Results: Of the 1,020 coinfected participants enrolled in the cohort, 707 (85%) had evidence of chronic HCV infection (HCV-RNA-positive), of whom 497 (70%) were infected with genotype 1; 375 (75%) were naive to HCV treatment and 122 (25%) had previously received therapy and failed. Only 143 (38%) of HCV treatment-naive and 39 (32%) of treatment-experienced participants had no absolute contraindications for treatment. Alcohol abuse, active depression and decompensated liver disease were the most frequent reasons for treatment ineligibility. The majority would require alterations in antiretroviral regimens to avoid important drug–drug interactions.

Conclusions: Although the need for curative HCV therapy in HIV–HCV coinfection is great, the actual number of patients who could be eligible for DAAs at the present time may be quite low. There remains an urgent need to develop safe, simple and interferon-sparing treatments for coinfected individuals.},
keywords = {Direct-acting antivirals, HCV, HCV therapy, HIV-HCV co-infection},
pubstate = {published},
tppubtype = {article}
}

@article{Hull2012,
title = {Insulin resistance is associated with progression to Hepatic fibrosis in a Cohort of HIV/HCV co-infected patients},
author = {Mark Hull and Kathleen C. Rollet-Kurhajec and Erica E. M. Moodie and Sharon Walmsley and Joseph Cox and Martin Potter and Curtis Cooper and Neora Pick and Sahar Saeed and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/22739388},
doi = {10.1097/QAD.0b013e32835612ce},
year = {2012},
date = {2012-09-10},
journal = {AIDS},
volume = {26},
number = {14},
pages = {1789-1794},
abstract = {OBJECTIVE:
Hepatitis C virus (HCV) infection is associated with higher insulin levels and insulin resistance. We evaluated factors associated with insulin resistance in a cohort of HIV/HCV-coinfected patients and determined the effect of insulin resistance on the development of hepatic fibrosis.
METHODS:
Data were analysed from 158 nondiabetic participants in a prospective Canadian cohort of HIV/HCV-coinfected patients. Patients were defined as having insulin resistance using the homeostasis model for assessment of insulin resistance (HOMA-IR) index. Factors associated with a high index (HOMA-IR ≥ 2) were identified using multivariate logistic regression. Incidence rates of liver fibrosis [aspartate aminotransferase- to-platelet ratio index (APRI) ≥ 1.5] were calculated, and multivariate time-dependent Cox regression models used to assess the effect of baseline insulin resistance on the risk of developing an APRI score of at least 1.5 during follow-up.
RESULTS:
Overall, 56% had baseline HOMA-IR of at least 2. In the adjusted multivariate logistic analysis, only baseline BMI of more than 25 kg/m2 remained associated with insulin resistance [adjusted odds ratio 3.66, 95% confidence interval (CI) 1.70-7.92]. Rates of progression to significant hepatic fibrosis (APRI ≥ 1.5) were higher in those with HOMA-IR of at least 2 (16.32 per 100 person-years, 95% CI 6.68-25.97) compared with those with HOMA-IR less than 2 (7.95 per 100 person-years, 95% CI 0.16-15.75). Baseline HOMA-IR of at least 2 was associated with the development of significant fibrosis (adjusted hazard ratio 7.71, 95% CI 2.55-23.36).},
keywords = {Hepatic Fibrosis, HIV-HCV co-infection, Insulin resistance},
pubstate = {published},
tppubtype = {article}
}

@article{Hull2012,
title = {Factors associated with discordance between absolute CD4 cell count and CD4 percentage in HIV/Hepatitis C (HCV) co-infected patients},
author = {Mark Hull and Kathleen C. Rollet-Kurhajec and Adefowope Odueyungbo and Sahar Saeed and Martin Potter and Joseph Cox and Curtis Cooper and John Gill and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/22460964},
doi = {10.1093/cid/cis289},
year = {2012},
date = {2012-06-15},
journal = {Clinical Infectious Diseases},
volume = {54},
number = {12},
pages = {1798-1805},
abstract = {BACKGROUND:
Liver cirrhosis has been associated with decreased absolute CD4 cell counts but preserved CD4 cell percentage in human immunodeficiency virus (HIV)-negative persons. We evaluated factors associated with discordance between the absolute CD4 cell count and the CD4 cell percentage in a cohort of patients coinfected with HIV and hepatitis C virus (HCV).
METHODS:
Baseline data from 908 participants in a prospective, Canadian, multisite cohort of individuals with HIV-HCV coinfection were analyzed. Absolute CD4 cell count and CD4 cell percentage relationships were evaluated. We defined low and high discordance between absolute CD4 cell count/CD4 cell percentage relationships as CD4 cell percentages that differed from the expected CD4 cell percentage, given the observed absolute CD4 cell count, by ±7 percentage points; we defined very low and very high discordance as differences of ±14 percentage points. Factors associated with high or very high discordance, including either end-stage liver disease or aspartate transaminase to platelet ratio index (APRI) of >1.5, were analyzed using multivariate logistic regression models and compared to groups with concordant and low discordant results.
RESULTS:
High/very high discordance was seen in 31% (n = 286), while 35% (n = 321) had concordant values. Factors associated with very high discordance at baseline included history of end-stage liver disease (adjusted odds ratio [aOR], 6.52; 95% confidence interval [CI], 2.27-18.67) and APRI of >1.5 (aOR 4.69; 95% CI, 1.64-13.35). Compared with those with detectable HCV RNA, those who cleared HCV spontaneously were less likely to have very high discordance.
CONCLUSIONS:
Discordance between absolute CD4 cell count and CD4 cell percentage is common in an HIV/HCV-coinfected population and is associated with advanced liver disease and ongoing HCV replication.},
keywords = {CD4, CD4 cell percentage, HIV-HCV co-infection},
pubstate = {published},
tppubtype = {article}
}