Research Papers

@article{W2017,
title = {Association Between Food Insecurity and HIV Viral Suppression: A Systematic Review and Meta-Analysis},
author = {Aibibula W and Cox J and Hamelin AM and McLinden T and Klein MB and Brassard P},
url = {https://pubmed.ncbi.nlm.nih.gov/27837425/},
doi = {10.1007/s10461-016-1605-5},
year = {2017},
date = {2017-03-21},
journal = {AIDS and Behaviour},
abstract = {Although an increasing number of HIV infected people are accessing antiretroviral treatment, many do not achieve complete HIV viral suppression and remain at risk for AIDS and capable of HIV transmission. Food insecurity has been identified as a potential risk factor for poor virologic response, but the association between these factors has been inconsistently documented in the literature. We systematically searched five electronic databases and bibliographies of relevant studies through April 2015 and retrieved 11 studies that met our inclusion criteria, of which nine studies were conducted in North America and the remaining two studies were in Brazil and Uganda respectively. Meta-analyzed results indicated that experiencing food insecurity resulted in 29% lower odds of achieving complete HIV viral suppression (OR = 0.71, 95% CI 0.61-0.82) and this significant inverse association was consistently found regardless of study design, exposure measurement, and confounder adjustment methods. These findings suggest that food insecurity is a potential risk factor for incomplete HIV viral suppression in people living with HIV.},
keywords = {Food insecurity, HIV, Meta-analysis, Viral suppression},
pubstate = {published},
tppubtype = {article}
}

@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{V2017,
title = {Cocaine/crack use is not associated with fibrosis progression measured by AST-to-Platelet Ratio Index in HIV-HCV co-infected patients: a cohort study},
author = {Martel-Laferrière V and Rollet-Kurhajec KC and Cox J and Cooper C and Tyndall M and Rouleau D and Walmsley S and Wong L and Klein MB},
doi = {10.1186/s12879-017-2196-0},
year = {2017},
date = {2017-01-17},
journal = {BMC Infect Dis.},
abstract = {Background: Cocaine and crack use has been associated with HIV and HCV infections, but its consequences on HCV progression have not been well established. We analyzed the impact of cocaine/crack use on liver fibrosis progression in a cohort of HIV-HCV co-infected patients.

Methods: A Canadian multicenter prospective cohort study followed 1238 HIV-HCV co-infected persons every 6 months between 2003 and 2013. Data were analyzed from 573 patients with positive HCV RNA, not on HCV treatment, without significant liver fibrosis (AST-to-Platelet Ratio Index (APRI) <1.5) or history of end-stage liver disease at baseline, and having at least two study visits. Recent cocaine/crack use was defined as use within 6 months of cohort entry. Incidence rates of progression to significant fibrosis (APRI ≥ 1.5) were determined according to recent cocaine/crack use. Cox Proportional Hazards models were used to assess the association between time-updated cocaine/crack use and progression to APRI ≥ 1.5 adjusting for age, sex, HCV duration, baseline ln(APRI), and time-updated alcohol abuse, history of other drug use and CD4+ cell count.

Results: At baseline, 211 persons (37%) were recent cocaine/crack users and 501 (87%) ever used cocaine/crack. Recent users did not differ from non-recent users on gender, age, and CD4+ T-cell count. Over 1599 person-years of follow up (522 PY in recent users, 887 PY in previous users and 190 PY in never users),158 (28%) persons developed significant fibrosis (9.9/100 PY; 95% CI, 8.3-11.4); 56 (27%) recent users (10.7/100 PY; 7.9-13.5), 81 (28%) previous users (9.1/100 PY; 7.1-11.1), and 21 (29%) never users (11.1/100 PY; 6.3-15.8). There was no association between ever having used or time-updated cocaine/crack use and progression to APRI ≥ 1.5 (adjusted HR (95%CI): 0.96 (0.58, 1.57) and 0.88;(0.63-1.25), respectively).

Conclusions: We could not find evidence that cocaine/crack use is associated with progression to advanced liver fibrosis in our prospective study of HIV-HCV co-infected patients.},
keywords = {APRI score, Cocaine, HIV, Liver fibrosis},
pubstate = {published},
tppubtype = {article}
}

@article{Aibibula2016,
title = {Food insecurity and low CD4 count among HIV-infected people: a systematic review and meta-analysis.},
author = {Wusiman Aibibula and Joseph Cox and Anne-Marie Hamelin and Hiroshi Mamiya and Marina B. Klein and Paul Brassard},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27306865},
doi = {10.1080/09540121.2016.1191613},
year = {2016},
date = {2016-06-16},
journal = {AIDS Care},
abstract = {Abstract
Food insecurity is defined as a limited or uncertain ability to acquire acceptable foods in socially acceptable ways, or limited or uncertain availability of nutritionally adequate and safe foods. While effective antiretroviral treatment can significantly increase CD4 counts in the majority of patients, there are certain populations who remain at relatively low CD4 count levels. Factors possibly associated with poor CD4 recovery have been extensively studied, but the association between food insecurity and low CD4 count is inconsistent in the literature. The objective is to systematically review published literature to determine the association between food insecurity and CD4 count among HIV-infected people. PubMed, Web of Science, ProQuest ABI/INFORM Complete, Ovid Medline and EMBASE Classic, plus bibliographies of relevant studies were systematically searched up to May 2015, where the earliest database coverage started from 1900. Studies that quantitatively assessed the association between food insecurity and CD4 count among HIV-infected people were eligible for inclusion. Study results were summarized using random effects model. A total of 2093 articles were identified through electronic database search and manual bibliographic search, of which 8 studies included in this meta-analysis. Food insecure people had 1.32 times greater odds of having lower CD4 counts compared to food secure people (OR = 1.32, 95% CI: 1.15-1.53) and food insecure people had on average 91 fewer CD4 cells/µl compared to their food secure counterparts (mean difference = -91.09, 95% CI: -156.16, -26.02). Food insecurity could be a potential barrier to immune recovery as measured by CD4 counts among HIV-infected people.},
keywords = {CD4, Food insecurity, HIV, Natural history, Nutrition/wasting},
pubstate = {published},
tppubtype = {article}
}

@article{LI2016,
title = {Trends in Incidences and Risk Factors for Hepatocellular Carcinoma and Other Liver Events in HIV and Hepatitis C Virus–coinfected Individuals From 2001 to 2014: A Multicohort Study},
author = {Gjærde LI and Shepherd L and Jablonowska E and Lazzarin A and Rougemont M and Darling K and Battegay M and Braun D and Martel-Laferriere V and Lundgren JD and Rockstroh JK and Gill J and Rauch A and Mocroft A and Klein MB and Peters L},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996136/},
doi = {10.1093/cid/ciw380},
year = {2016},
date = {2016-06-15},
journal = {Clinical Infectious Diseases},
abstract = {Background. While liver-related deaths in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)–coinfected individuals have declined over the last decade, hepatocellular carcinoma (HCC) may have increased. We describe the epidemiology of HCC and other liver events in a multicohort collaboration of HIV/HCV–coinfected individuals.

Methods. We studied HCV antibody-positive adults with HIV in the EuroSIDA study, the Southern Alberta Clinic Cohort, the Canadian Co-infection Cohort, and the Swiss HIV Cohort study from 2001 to 2014. We calculated the incidence of HCC and other liver events (defined as liver-related deaths or decompensations, excluding HCC) and used Poisson regression to estimate incidence rate ratios.

Results. Our study comprised 7229 HIV/HCV–coinfected individuals (68% male, 90% white). During follow-up, 72 cases of HCC and 375 other liver events occurred, yielding incidence rates of 1.6 (95% confidence interval [CI], 1.3, 2.0) and 8.6 (95% CI, 7.8, 9.5) cases per 1000 person-years of follow-up, respectively. The rate of HCC increased 11% per calendar year (95% CI, 4%, 19%) and decreased 4% for other liver events (95% CI, 2%, 7%), but only the latter remained statistically significant after adjustment for potential confounders. Older age, cirrhosis, and low current CD4 cell count were associated with a higher incidence of both HCC and other liver events.

Conclusions. In HIV/HCV–coinfected individuals, the crude incidence of HCC increased from 2001 to 2014, while other liver events declined. Individuals with cirrhosis or low current CD4 cell count are at highest risk of developing HCC or other liver events.},
keywords = {Cohort study, HCV, Hepatocellular carcinoma, HIV, Liver disease},
pubstate = {published},
tppubtype = {article}
}

@article{Rossi2016,
title = {Frequent injection cocaine use increases the risk of renal impairment among Hepatitis C and HIV co-infected patients},
author = {Carmine Rossi and Joseph Cox and Curtis Cooper and Valérie Martel-Laferrière and Sharon Walmsley and John Gill and Ruth Sapir-Pichhadze and Erica E. M. Moodie and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26859371},
doi = {10.1097/QAD.0000000000001060},
year = {2016},
date = {2016-06-01},
journal = {AIDS},
abstract = {OBJECTIVE:
To examine the association between injection cocaine use, hepatitis C virus (HCV) infection, and chronic renal impairment (CRI).
DESIGN:
Prospective observational cohort study of HIV-HCV coinfected patients.
METHODS:
Data from 1129 participants in the Canadian Co-Infection Cohort with baseline and follow-up serum creatinine measurements between 2003 and 2014 were analyzed. Prevalent and incident cohorts were created to examine the association between self-reported past, current, and cumulative cocaine use and chronic HCV with CRI. CRI was defined as an estimated glomerular filtration rate below 70 ml/min per 1.73 m. Multivariate logistic regression was used to calculate odds ratios, and discrete-time proportional-hazards models were used to calculate hazard ratios for cocaine use, in the two respective cohorts, adjusted for HCV RNA and important demographic, HIV disease stage, and comorbidity confounders.
RESULTS:
Eighty-seven participants (8%) had prevalent CRI. Past injection cocaine use was associated with a two-fold greater risk of prevalent CRI [odds ratio 2.03, 95% confidence interval (CI) 0.96, 4.32]. During follow-up, 126 of 1061 participants (12%) developed incident CRI (31 per 1000 person-years). Compared to nonusers, heavy (≥ 3 days/week) and frequent injection cocaine users (≥75% of follow-up time) experienced more rapid progression to CRI (hazard ratio 2.65, 95% CI 1.35, 5.21; and hazard ratio 1.82, 95% CI 1.07, 3.07, respectively). There was no association between chronic HCV and CRI in either cohort.
CONCLUSION:
After accounting for HCV RNA, frequent and cumulative injection cocaine abuse was associated with CRI progression and should be taken into consideration when evaluating impaired renal function in HIV-HCV coinfection.},
keywords = {Chronic hepatitis C, Co-infection, Cocaine, HIV, Intravenous substance abuse, Renal insufficiency},
pubstate = {published},
tppubtype = {article}
}

@article{Young2016,
title = {Fibroblast growth factor 23: associations with antiretroviral therapy in patients co-infected with HIV and hepatitis C},
author = {James Young and Istvan Mucsi and Kathleen C. Rollet-Kurhajec and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26307135},
doi = {10.1111/hiv.12305},
year = {2016},
date = {2016-05-15},
journal = {HIV Med},
abstract = {OBJECTIVES:
Fibroblast growth factor 23 (FGF23) has been associated with cardiovascular mortality. We estimate associations between the level of plasma FGF23 and exposure to abacavir (ABC) and to other components of antiretroviral therapy in patients co-infected with HIV and hepatitis C.
METHODS:
Both intact and c-terminal FGF23 were measured in plasma using commercial assays for a sub-cohort of 295 patients selected at random from the 1150 patients enrolled in the Canadian Co-infection Cohort. The multiplicative effects of antiretroviral drug exposures and covariates on median FGF23 were then estimated using a hierarchical Bayesian model.
RESULTS:
The median level of intact FGF23 was independent of either past or recent exposure to abacavir, with multiplicative ratios of 1.00 and 1.07, 95% credible intervals 0.90-1.12 and 0.94-1.23, respectively. Median intact FGF23 tended to increase with past use of both nonnucleoside reverse-transcriptase inhibitors and protease inhibitors, but tended to decrease with recent use of either tenofovir, efavirenz or lopinavir. There were no obvious associations between the median level of c-terminal FGF23 and individual drugs or drug classes. Age, female gender, smoking and the aspartate aminotransferase to platelet ratio index were all associated with a higher median c-terminal FGF23 but not with a higher median intact FGF23.
CONCLUSIONS:
The level of FGF23 in plasma was independent of exposure to ABC. Lower levels of intact FGF23 with recent use of tenofovir, efavirenz or lopinavir may reflect their adverse effects on bone and vitamin D metabolism relative to other drugs in their respective drug classes.
© 2015 British HIV Association.},
keywords = {Antiretroviral therapy, Fibroblast growth factor 23, HCV, HIV},
pubstate = {published},
tppubtype = {article}
}

@article{Costiniuk2016,
title = {Tobacco Smoking Is Not Associated With Accelerated Liver Disease in Human Immunodeficiency Virus-Hepatitis C Coinfection: A Longitudinal Cohort Analysis},
author = {Cecilia T. Costiniuk and Laurence Brunet and Kathleen C. Rollet-Kurhajec and Curtis Cooper and Sharon Walmsley and M. John Gill and Valérie Martel-Laferriere and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27047987},
doi = {10.1093/ofid/ofw050},
year = {2016},
date = {2016-03-04},
journal = {Open Forum Infectious Diseases},
abstract = {Background.  Tobacco smoking has been shown to be an independent risk factor for liver fibrosis in hepatitis C virus (HCV) infection in some cross-sectional studies. No longitudinal study has confirmed this relationship, and the effect of tobacco exposure on liver fibrosis in human immunodeficiency virus (HIV)-HCV coinfected individuals is unknown. Methods.  The study population consisted of participants from the Canadian Co-infection Cohort study (CTN 222), a multicenter longitudinal study of HIV-HCV coinfected individuals from 2003 to 2014. Data were analyzed for all participants who did not have significant fibrosis or end-stage liver disease (ESLD) at baseline. The association between time-updated tobacco exposure (ever vs nonsmokers and pack-years) and progression to significant liver fibrosis (defined as an aspartate-to-platelet ratio index [APRI] ≥1.5) or ESLD was assessed by pooled logistic regression. Results.  Of 1072 participants included in the study, 978 (91%) had ever smoked, 817 (76%) were current smokers, and 161 (15%) were previous smokers. Tobacco exposure was not associated with accelerated progression to significant liver fibrosis nor with ESLD when comparing ever vs never smokers (odds ratio [OR] = 1.06, 95% confidence interval [CI], 0.43-1.69 and OR = 1.20, 95% CI, 0.21-2.18, respectively) or increases in pack-years smoked (OR = 1.05, 95% CI, 0.97-1.14 and OR = 0.94, 95% CI, 0.83-1.05, respectively). Both time-updated alcohol use in the previous 6 months and presence of detectable HCV ribonucleic acid were associated with APRI score ≥1.5. Conclusions.  Tobacco exposure does not appear to be associated with accelerated progression of liver disease in this prospective study of HIV-HCV coinfected individuals.},
keywords = {Cohort study, HCV, HIV, Liver disease, Tobacco},
pubstate = {published},
tppubtype = {article}
}

@article{Brunet2016,
title = {Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C-Coinfected Persons},
author = {Laurence Brunet and Erica E. M. Moodie and Jim Young and Joseph Cox and Mark Hull and Curtis Cooper and Sharon Walmsley and Valérie Martel-Laferrière and Anita Rachlis and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26400998},
doi = {10.1093/cid/civ838},
year = {2016},
date = {2016-01-15},
journal = {Clinical Infectious Diseases},
abstract = {BACKGROUND:
Liver diseases progress faster in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV-coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC).
METHODS:
Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction-positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent.
RESULTS:
A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, -3%, 19%) or NNRTI users (3% per 5 years, 95% CI, -7%, 12%).
CONCLUSIONS:
Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV-coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used.
© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

},
keywords = {APRI, Combination antiretroviral therapy, HCV, HIV, Liver fibrosis},
pubstate = {published},
tppubtype = {article}
}

@article{Brunet2016,
title = {Opioid use and risk of liver fibrosis in HIV/hepatitis C virus-coinfected patients in Canada},
author = {Laurence Brunet and Erica E. M. Moodie and Joseph Cox and John Gill and Curtis Cooper and Sharon Walmsley and Anita Rachlis and Mark Hull and Marina B. Klein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26140381},
doi = {10.1111/hiv.12279},
year = {2016},
date = {2016-01-05},
journal = {HIV Med},
abstract = {OBJECTIVES:
Opioid use and opioid-related mortality have increased dramatically since the 1990s in North America. The effect of opioids on the liver is incompletely understood. Some studies have suggested that opioids cause liver damage and others have failed to show any harm. HIV/hepatitis C virus (HCV)-coinfected persons may be particularly vulnerable to factors increasing liver fibrosis. We aimed to describe opioid use in an HIV/HCV-coinfected population in Canada and to estimate the association between opioid use and liver fibrosis.
METHODS:
We conducted a cross-sectional descriptive analysis of the Canadian Co-infection Cohort Study data to characterize opioid use. We then conducted a longitudinal analysis to assess the average change in aspartate aminotransferase-to-platelet ratio index (APRI) score associated with opioid use using a generalized estimating equation with linear regression. We assessed the progression to significant liver fibrosis (APRI ≥ 1.5) associated with opioid use with pooled logistic regression.
RESULTS:
In the 6 months preceding cohort entry, 32% of the participants had received an opioid prescription, 28% had used opioids illicitly and 18% had both received a prescription and used opioids illicitly. Neither prescribed nor illicit opioid use was associated with a change in the median APRI score [exp(β) 0.99 (95% confidence interval (CI) 0.82, 1.12) and exp(β) 0.95 (95% CI 0.81, 1.10), respectively] or with faster progression to liver fibrosis [hazard odds ratio (HOR) 1.20 (95% CI 0.73, 1.67) and HOR 1.09 (95% CI 0.63, 1.55), respectively].
CONCLUSIONS:
Although opioids were commonly used both legally and illegally in our cohort, we were unable to demonstrate a negative impact on liver fibrosis progression.
© 2015 British HIV Association.},
keywords = {HCV, HIV, Liver fibrosis, Opioids},
pubstate = {published},
tppubtype = {article}
}