Research Papers

@article{Yeung2015,
title = {Changes in quality of life, health care use and substance use in HIV- Hepatitis C coinfected patients after Hepatitis C therapy: a prospective Cohort study},
author = {Man Wah Yeung and Jim Young and Erica E. M. Moodie and Kathleen C. Rollet-Kurhajec and Kevin Schwartzman and Christina Greenaway and Curtis Cooper and Joseph Cox and John Gill and Mark Hull and Sharon Walmsley and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25972048},
doi = {10.1179/501100000024},
year = {2015},
date = {2015-05-14},
journal = {HIV Clinical Trials},
abstract = {OBJECTIVE:
Clinical benefits of achieving a sustained virologic response (SVR) with hepatitis c virus (HCV) therapy beyond reducing liver-related outcomes have not been documented in HIV-coinfected patients, who have multiple competing health problems. To gauge the potential benefits of curing HCV in coinfected people, we examined changes in health-related quality of life (HRQOL), healthcare and substance use, and overall mortality after treatment for HCV Coinfection.
DESIGN:
Prospective multicentre cohort study.
METHODS:
Among patients treated for HCV in the Canadian Coinfection Cohort study, self-reported HRQOL (using the EQ-5D), inpatient and outpatient medical visits, and substance use were assessed before, 6 months and 1 year after completing HCV therapy, comparing SVR-achievers and non-responders. Analysis of covariance and zero-inflated negative binomial regression were used to model the effects of SVR on HRQOL and healthcare use, respectively.
RESULTS:
Of 1145 patients chronically infected with HCV, 223 (19%) received treatment while under follow-up in the cohort and had HRQOL data collected - 86 (36%) achieved SVR, 68 (29%) did not, 30 (13%) had ongoing treatment, and 39 (17%) had unknown responses. Compared to non-responders, those achieving a SVR had higher HRQOL scores over time (11-unit increase 1 year posttreatment, 95% CI: 2, 21 measured 1 year posttreatment) and a lower rate of health service utilization (adjusted incidence rate ratio: 0.5, 95% CI: 0.3, 0.9). Short-term mortality was low but appeared lower in SVR-achievers (incidence rates: 0.10 vs 0.12 deaths per 100 person-years). However, after successful treatment, a substantial number of patients increased alcohol consumption and continued to inject drugs.
CONCLUSIONS:
Successful HCV treatment results in a range of health benefits for HIV/HCV-coinfected patients. Ongoing substance use, however, may mitigate the short- and long-term benefits associated with curing HCV.},
keywords = {HCV virus treatment, Health services, HIV, Mortality, Quality of life, Sustained virologic response},
pubstate = {published},
tppubtype = {article}
}

@article{Cooper2015,
title = {HIV virological rebounds but not blips predict liver fibrosis progression in antiretroviral-treated HIV/hepatitis C virus-coinfected patients},
author = {Curtis Cooper and Kathleen C. Rollet-Kurhajec and Jim Young and Colins Vasquez and Mark Tyndall and John Gill and Neora Pick and Sharon Walmsley and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24837567},
doi = {10.1111/hiv.12168},
year = {2015},
date = {2015-01-15},
journal = {HIV Med},
volume = {16},
number = {1},
pages = {24-31},
abstract = {OBJECTIVES:
Antiretroviral interruption is associated with liver fibrosis progression in HIV/hepatitis C virus (HCV) coinfection. It is not known what level of HIV viraemia affects fibrosis progression.
METHODS:
We evaluated 288 HIV/HCV-coinfected cohort participants with undetectable HIV RNA (<50 HIV-1 RNA copies/mL) on two consecutive visits while on combination antiretroviral therapy (cART) without fibrosis [aspartate aminotransferase to platelet ratio index (APRI) <1.5], end-stage liver disease or HCV therapy. An HIV blip was defined as a viral load of ≥ 50 and <1000 copies/mL, preceded and followed by undetectable values. HIV rebound was defined as: (i) HIV RNA ≥ 50 copies/mL on two consecutive visits, or (ii) a single HIV RNA measurement ≥ 1000 copies/mL. Multivariate discrete-time proportional hazards models were used to assess the effect of different viraemia levels on liver fibrosis progression (APRI ≥ 1.5).
RESULTS:
The mean age of the patients was 45 years, 74% were male, 81% reported a history of injecting drug use, 51% currently used alcohol and the median baseline CD4 count was 440 [interquartile range (IQR) 298, 609] cells/μL. Fifty-seven (20%) participants [12.4/100 person-years (PY); 95% confidence interval (CI) 9.2-15.7/100 PY] progressed to an APRI ≥ 1.5 over a mean 1.1 (IQR 0.6, 2.0) years of follow-up time at risk. Virological rebound [hazard ratio (HR) 2.3; 95% CI 1.1, 4.7] but not blips (HR 0.5; 95% CI 0.2, 1.1) predicted progression to APRI ≥ 1.5. Each additional 1 log10 copies/mL HIV RNA exposure (cumulative) was associated with a 20% increase in the risk of fibrosis progression (HR 1.2; 95% CI 1.0-1.3).
CONCLUSIONS:
Liver fibrosis progression was associated with HIV rebound, but not blips, and with increasing cumulative exposure to HIV RNA, highlighting the importance of achieving and maintaining HIV suppression in the setting of HIV/HCV coinfection.
© 2014 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.},
keywords = {Fibrosis, HCV, HIV, Virological blips, Virological rebound},
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{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{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}
}

@article{Al-Mohri2007,
title = {Evaluating liver fibrosis progression and the impact of antiretroviral therapy in HIV and Hepatitis C coinfection using a noninvasive marker},
author = {Huda Al-Mohri and Tanya Murphy and Ying Lu and Richard G. Lalonde and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/17211282},
doi = {10.1097/QAI.0b013e318030ff8e},
year = {2007},
date = {2007-04-01},
journal = {JAIDS},
volume = {44},
number = {4},
pages = {463-469},
abstract = {The effects of highly active antiretroviral therapy (HAART) on progression of hepatic fibrosis in hepatitis C virus (HCV) coinfection with HIV are not well understood and are difficult to measure because of the need for repeated liver biopsy. We evaluated the evolution of a noninvasive measure of liver fibrosis, the alanine aspartyl transferase (AST)-to-platelet ratio index (APRI), longitudinally and determined its predictive value for hepatic outcomes in HIV-positive patients with and without HCV coinfection. A total of 673 HIV-positive patients without liver complications at baseline (540 with HIV only, 133 with HIV-HCV coinfection) were followed between 1991 and 2004 for a median of 4.6 years (3524 person-years). At baseline, HIV-HCV coinfection had a higher median APRI compared with HIV infection alone (0.59 vs. 0.33; P < 0.0001). The natural logarithm of the APRI [ln(APRI)] changed significantly over time, particularly among patients with HIV-HCV coinfection. The baseline ln(APRI) was predictive of liver complications (hazard ratio [HR] = 4.0, 95% confidence interval [CI]: 2.5 to 6.4 per log), as was HCV (HR = 4.5, 95% CI: 1.5 to 14). Cumulative HAART did not protect against liver complications, although it was significantly associated with progression of APRI scores in HIV-HCV coinfection and in HIV alone. In conclusion, the APRI may be a useful marker for longitudinal evaluation of the progression of liver disease in HIV-HCV coinfection.},
keywords = {Alanine aspartyl transferase-to-platelet ratio index, Antiretroviral therapy, HCV, Hepatic Fibrosis, HIV},
pubstate = {published},
tppubtype = {article}
}