Documents de recherche

@article{Thorpe2011,
title = {Antiretroviral treatment interruption leads to progression of liver fibrosis in HIV-Hepatitis C virus Co-infection},
author = {Julia Thorpe and Sahar Saeed and Erica E. M. Moodie and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/21330904},
doi = {10.1097/QAD.0b013e3283455e4b},
year = {2011},
date = {2011-04-24},
journal = {AIDS},
volume = {25},
number = {7},
pages = {967-975},
abstract = {OBJECTIVE:
Despite potential negative consequences, HIV/hepatitis C virus (HCV) co-infected patients may discontinue antiretroviral treatment (ART) for several reasons. We examined the impact of ART interruption on liver fibrosis progression in co-infected adults, using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate marker of liver fibrosis.
METHOD:
Data were analyzed from a multisite prospective cohort of 541 HIV-HCV co-infected adults. ART interruption was included as a time-updated variable and defined as the cessation of all antiretrovirals for at least 14 days. The primary endpoint was the development of an APRI score at least 1.5. Time-dependent Cox proportional hazards regression and inverse probability-of-treatment weighting (IPTW) in a marginal structural model were used to evaluate the association of baseline and time-varying covariates with developing significant fibrosis.
RESULTS:
Patients were followed for a median of 1.02 years; 10% (n = 53) interrupted ART and 10% (n = 53) developed significant fibrosis. After accounting for potential confounders, including CD4 T-cell count, HIV viral load, baseline APRI score, age and gender, the hazard ratio for ART interruption was 2.52 (95% confidence interval 1.20-5.28). Use of IPTW resulted in a similar effect estimate, suggesting that mediation by time-varying confounders was negligible.
CONCLUSION:
ART interruption was associated with an increased risk of fibrosis progression in HIV-HCV co-infection that was only partially accounted for by HIV viral load and CD4 T-cell counts. Our findings suggest that liver disease progression observed in ART-treated co-infected patients is partly due to the consequences of treatment interruptions.},
keywords = {Antiretroviral therapy, HIV-HCV co-infection, Liver fibrosis},
pubstate = {published},
tppubtype = {article}
}

@article{Rizza2010,
title = {Polymorphism in tumor necrosis factor-related apoptosis-inducing ligand receptor 1 is associated with poor viral response to interferon-based Hepatitis C virus therapy in HIV/Hepatitis C virus-coinfected individuals},
author = {Stacey A. Rizza and Nathan W. Cummins and David N. Rider and Sahar Saeed and Marina B. Klein and Andrew D. Badley},
url = {https://www.ncbi.nlm.nih.gov/pubmed/20802294},
doi = {10.1097/QAD.0b013e32833eacfd},
year = {2010},
date = {2010-11-15},
journal = {AIDS},
volume = {24},
number = {17},
pages = {2639-2644},
abstract = {OBJECTIVE(S):
HIV/hepatitis C virus (HCV) coinfection causes accelerated liver disease compared to HCV monoinfection, and only 30-60% of HIV/HCV-coinfected individuals respond to HCV therapy with pegylated interferon and ribavirin. There are currently no biomarkers that predict treatment response in these coinfected patients.
DESIGN:
We investigated whether there is an association between HCV treatment response and SNPs of apoptosis-related genes during HIV/HCV coinfection.
METHOD:
Genomic DNA from 53 HIV/HCV-coinfected individuals was analyzed for 82 SNPs of 10 apoptosis-related genes.
RESULTS:
We found that the presence of the rs4242392 SNP in tumor necrosis factor receptor superfamily, member 10a (TNFRSF10A), which encodes for tumor necrosis factor-related apoptosis-inducing ligand receptor 1, predicts poor outcome to HCV therapy, in HIV/HCV-co-infected patients [odds ratio 5.91 (95% confidence interval 1.63-21.38, P = 0.007)].
CONCLUSION:
The rs4242392 SNP of the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 gene predicted poor interferon-based HCV treatment response in HIV/HCV-coinfected patients.},
keywords = {Apoptosis-inducing ligand receptor 1, HIV-HCV co-infection, Polymorphism, Tumor necrosis},
pubstate = {published},
tppubtype = {article}
}

@article{Vali2010,
title = {HCV-specific T cells in HCV/HIV Co-infection show elevated frequencies of dual Tim-3/PD-1 expression that correlate with liver disease progression},
author = {Bahareh Vali and R. Brad Jones and Ali Sakhdari and Prameet M. Sheth and Kiera Clayton and Feng-Yun Yue and Gabor Gyenes and David Wong and Marina B. Klein and Sahar Saeed and Erika Benko and Colin Kovacs and Rupert Kaul and Mario A. Ostrowski},
url = {https://www.ncbi.nlm.nih.gov/pubmed/20623550},
doi = {10.1002/eji.201040340},
year = {2010},
date = {2010-09-01},
journal = {European Journal of Immunology},
volume = {40},
number = {9},
pages = {2493-2505},
abstract = {Co-infection of HCV with HIV has been associated with more rapid progression of HCV-related disease. HCV-specific T-cell immune responses, which are essential for disease control, are attenuated in co-infection with HIV. T-cell exhaustion has recently been implicated in the deficient control of chronic viral infections. In the current study, we investigated the role of programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) expression in T-cell exhaustion during HCV/HIV co-infection. We show that in HCV/HIV co-infection, both total and HCV-specific T cells co-express Tim-3 and PD-1 in significantly higher frequencies, compared with HCV mono-infection. Co-expression of these two markers on HCV-specific CD8(+) T cells positively correlated with a clinical parameter of liver disease progression. HCV-specific CD8(+) T cells showed greater frequencies of Tim-3/PD-1 co-expression than HIV-specific CD8(+) T cells, which may indicate a greater degree of exhaustion in the former. Blocking Tim-3 or PD-1 pathways restored both HIV- and HCV-specific CD8(+) T-cell expansion in the blood of co-infected individuals. These data demonstrate that co-expression of Tim-3 and PD-1 may play a significant role in HCV-specific T-cell dysfunction, especially in the setting of HIV co-infection.},
keywords = {HIV-HCV co-infection, Liver disease, T-cell exhaustion},
pubstate = {published},
tppubtype = {article}
}

@article{Potter2010,
title = {Impact of Hepatitis C viral replication on CD4+ T-lymphocyte progression in HIV-Co-infection before and after antiretroviral therapy},
author = {Martin Potter and Adefowope Odueyungbo and Hong Yang and Sahar Saeed and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/20479633},
doi = {10.1097/QAD.0b013e32833adbb5},
year = {2010},
date = {2010-07-31},
journal = {AIDS},
volume = {24},
number = {12},
pages = {1857-1865},
abstract = {OBJECTIVE:
HIV is known to have a negative impact on the progression of hepatitis C virus (HCV) infection, whereas the reverse remains unclear. We examined the impact of spontaneous clearance of HCV on CD4(+) T-lymphocyte count progression before and after initiation of antiretroviral therapy (ART) in HIV-HCV coinfected adults.
METHODS:
Data were analysed from participants in a Canadian, multisite prospective cohort of HIV-infected adults with serologic evidence of HCV infection. The rate of CD4(+) T-lymphocyte change was determined using multivariate mixed linear regression comparing chronically HCV RNA+ with spontaneous clearers (persistently HCV RNA- without HCV therapy).
RESULTS:
Baseline characteristics of the 271 participants analysed did not differ between individuals whose HCV RNA cleared (n = 35) and those whose HCV RNA persisted (n = 236) except with respect to markers of liver disease. HCV RNA+ individuals had on average seven-times slower recovery of CD4(+) T-cells on chronic ART compared with HCV RNA-: (adjusted change in absolute CD4 cell T-lymphocyte count per year: 4 (95% confidence interval, -0.6 to 8) cells/microl vs. 26 (95% confidence interval, 12 to 41) cells/microl; P < 0.001. Analyses restricted to individuals initiating ART showed similar results. There was also a trend to greater CD4 decline prior to ART initiation among those HCV RNA+, although this did not reach statistical significance.
CONCLUSION:
We found that CD4 cell progression is negatively affected by the presence of ongoing HCV replication in coinfected individuals initiating ART which persisted throughout stable ART suggesting active HCV infection affects immune restoration even after years of ART exposure.},
keywords = {Antiretroviral therapy, CD4, HIV-HCV co-infection, T-lymphocyte progression, Viral replication},
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{Moodie2009,
title = {Is antiretroviral therapy causing long-term liver damage? A comparative analysis of HIV-mono-infected and HIV/Hepatitis C co-infected Cohorts},
author = {Erica E. M. Moodie and Nitika Pant Pai and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/19223976},
doi = {10.1371/journal.pone.0004517},
year = {2009},
date = {2009-02-18},
journal = {PLoS One},
volume = {4},
number = {2},
abstract = {The effects of highly active antiretroviral therapy (HAART) on progression of hepatic fibrosis in HIV-hepatitis C virus (HCV) co-infection are not well understood. Deaths from liver diseases have risen in the post-HAART era, yet some cross-sectional studies have suggested that HAART use is associated with improved fibrosis rates. In a retrospective cohort of 533 HIV mono-infected and 127 HIV/HCV co-infected patients, followed between January 1991 and July 2005 at a university-based HIV clinic, we investigated the relationship between cumulative HAART exposure and hepatic fibrosis, as measured by the aspartate aminotransferase-to-platelet ratio index (APRI). We used a novel methodological approach to estimate the dose-response relationship of the effect of HAART exposure on APRI. HAART was associated with increasing APRI over time in HIV/HCV co-infected patients suggesting that they may be experiencing cumulative hepatotoxicity from antiretrovirals. The estimated median change (95% confidence interval) in APRI per one year of HAART intake was of -0.46% (-1.61% to 0.71%) in HIV mono-infected compared to 2.54% (-1.77% to 7.03%) in HIV/HCV co-infected patients. Similar results were found when the direct effect of HAART intake since the last visit was estimated on the change in APRI. HAART use associated is with increased APRI in patients with HIV/HCV co-infection. Therefore treatment for HCV infection may be required to slow the growing epidemic of end-stage liver disease in this population.},
keywords = {Antiretroviral therapy, HIV mono-infection, HIV-HCV co-infection, Liver damage},
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}
}

@article{Al-Mohri2005,
title = {Validation of a simple model for predicting liver fibrosis in HIV/Hepatitis C (HCV) co-infected patients},
author = {Huda Al-Mohri and Curtis Cooper and Tanya Murphy and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/16268817},
doi = {10.1111/j.1468-1293.2005.00330.x},
year = {2005},
date = {2005-10-15},
journal = {HIV Med},
volume = {6},
number = {6},
pages = {375-378},
abstract = {OBJECTIVES:
Recently, several models incorporating laboratory measurements have been validated for use as surrogate markers for liver fibrosis in hepatitis C virus (HCV) mono-infection, the simplest of these being the aspartate aminotransferase (AST) to platelet ratio index (APRI). We evaluated how well the APRI predicts significant hepatic fibrosis in patients with HIV/HCV coinfection.
METHODS:
Forty-six HIV/HCV-coinfected patients who underwent liver biopsy and had concomitant laboratory measurements (+/-3 months) were included in the study. Significant fibrosis was defined as F2-F4 using Batt and Ludwig scoring (=3 Ishak). APRI=[(AST/upper limit of normal)/platelet count (10(9)/L)] x 100. We used sas proc logistic (SAS Institute, Cary, NC) to calculate the area under the receiver operating curve (ROC) (AUC). Sensitivities, specificities, positive predictive value (PPV) and negative predictive value (NPV) were compared using cut-offs previously identified in the literature.
RESULTS:
Thirty-three of 46 patients (72%) had significant fibrosis on biopsy. For significant fibrosis, the area under the ROC for the APRI was 0.847+/-0.057. APRI scores >1.5 (the higher cut-off) were 100% specific and 52% sensitive; PPV was 100% and NPV 45%. Scores <0.5 (the lower cut-off) were 82% sensitive and 46% specific in ruling out significant fibrosis (PPV 79%; NPV 50%).
CONCLUSIONS:
A simple model incorporating readily available laboratory data is highly predictive of significant fibrosis in HIV/HCV coinfection and could serve as a biopsy-sparing measure, thus making treatment more accessible for this population.},
keywords = {HIV-HCV co-infection, Liver fibrosis},
pubstate = {published},
tppubtype = {article}
}

@article{MB2003,
title = {The Impact of Hepatitis C Co-infection on HIV Progression Before and After Highly Active Antiretroviral Therapy. },
author = {Klein MB and Lalonde RG and Suissa S},
url = {https://www.natap.org/2003/aug/081803_6.htm},
year = {2003},
date = {2003-01-01},
journal = {JAIDS},
keywords = {HAART, HCV, HIV-HCV co-infection},
pubstate = {published},
tppubtype = {article}
}