Research Papers

@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}
}

@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{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{Kared2014,
title = {CD127 Expression, Exhaustion Status and Antigen Specific Proliferation Predict Sustained Virologic Response to IFN in HCV/HIV Co-Infected Individuals},
author = {Hassen Kared and Sahar Saeed and Marina B. Klein and Naglaa H. Shoukry},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25007250},
doi = {10.1371/journal.pone.0101441},
year = {2014},
date = {2014-07-09},
journal = {PLoS One},
volume = {9},
number = {7},
abstract = {Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in the HIV co-infected population. Interferon-alpha (IFN-α) remains a major component of anti-HCV therapy despite its deleterious effects on the immune system. Furthermore, IFN-α was recently shown to diminish the size of the latent HIV reservoir. The objectives of this study were to monitor the impact of IFN-α on T cell phenotype and proliferation of HIV and HCV-specific T cells during IFN therapy, and to identify immune markers that can predict the response to IFN in HICV/HIV co-infected patients. We performed longitudinal analyses of T cell numbers, phenotype and function in co-infected patients undergoing IFN-α therapy with different outcomes including IFN-α non-responders (NR) (n = 9) and patients who achieved sustained virologic response (SVR) (n = 19). We examined the expression of activation (CD38, HLA-DR), functional (CD127) and exhaustion markers (PD1, Tim-3, CD160 and CD244) on total CD4 and CD8 T cells before, during and after therapy. In addition, we examined the HIV- and HCV-specific proliferative responses against HIV-p24 and HCV-NS3 proteins. Frequencies of CD127+ CD4 T cells were higher in SVR than in NR patients at baseline. An increase in CD127 expression on CD8 T cells was observed after IFN-α therapy in all patients. In addition, CD8 T cells from NR patients expressed a higher exhaustion status at baseline. Finally, SVR patients exhibited higher proliferative response against both HIV and HCV antigens at baseline. Altogether, SVR correlated with higher expression of CD127, lower T cell exhaustion status and better HIV and HCV proliferative responses at baseline. Such factors might be used as non-invasive methods to predict the success of IFN-based therapies in co-infected individuals.},
keywords = {HCV, HIV-HCV co-infection, Interferon alpha, Mortality, Sustained virologic response},
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}
}