About the study
Initiated in Montreal in 2002 and funded by CIHR in 2005, the Canadian Co-infection Cohort Study received support from the CTN starting in 2007. This national cohort study examines the effect of antiretroviral therapy (ART) on liver disease progression in people living with both HIV and hepatitis C virus (HCV). CTN 222 was the first observational cohort study approved by the CTN and included 950 participants from across 16 sites. With renewed funding from CIHR in 2009, and again in 2014, CTN 222 has expanded to include over 1600 people living with HCV and HIV.
HCV is a virus that attacks the liver, causing liver disease (hepatitis). Because HCV can be contracted through the same routes as HIV (blood-to-blood contact, sexual contact, etc.) over 30% of people living with HIV worldwide also have HCV. Due to the success of antiretroviral therapies (ART), complications from comorbidities such as HCV have replaced AIDS-related infections as the primary health concern among people living with HIV.
End-stage liver disease (ESLD) due to HCV is one of the leading causes of illness and death in HIV/HCV+ people. The natural course of HCV is accelerated in people living with HIV. Initially, the ability of ART to restore the immune system was expected to improve liver health in this population. This was not the case, however, and liver disease continues to be a significant problem. In response, CTN 222 was formed to document and understand the social and biological factors that contribute to the interaction between these two viruses and their treatment and management.
CTN 222 is a long-term observational cohort study and includes a diverse group of people including men who have sex with men (MSM), current and ex-injection drug users, Indigenous people, and women. All eligible individuals who visit a participating clinic are invited to participate in the study. Those who initially decline the invitation are eligible to enrol in the future.
- HIV treatment naïve
- Aged 16 years or older (or as provincial guidelines)
- Documented HIV seropositive infection
- Documented HCV infection or evidence of exposure
- Able to provide informed consent
After giving informed consent and undergoing an initial evaluation, CTN 222 participants return approximately every 6 months, either as a part of clinical care or for study purposes alone. Clinical, sociodemographic, behavioural, medical, and treatment information is collected. Treatment and diagnosis history is also collected from past medical visits.
Since 2010, the CTN 222 team has published over 30 journal articles. This body of work is expansive, stretching across different areas of this complex area; this includes general cohort information, the effect of different treatment regimens, the impact of immunological factors, genetic variations, and lifestyle factors, and the interaction between participant sub-groups and liver-related health. One such characteristic is the effect of food insecurity on HIV-HCV outcomes which has spawned a CTN 222 sub-study, CTN 264.
Saeed S, Moodie EEM, Strumpf EC, Klein MB. Evaluating the impact of health policies: using a difference-in-differences approach. Int J Public Health. 2019 Jan 3 epub ahead of print.
Nitulescu R, Young J, Saeed S, Cooper C, Cox J, Martel-Laferrière V, Hull MW, Walmsley SL, Tyndall M, Wong A, Klein MB; Canadian Co-Infection Cohort Study. Variation in hepatitis C virus treatment uptake between Canadian centres in the era of direct-acting antivirals. Int J Drug Policy. 2018 Dec 26;65:41-49.
Saeed S, Moodie EE, Strumpf E, Gill JS, Wong A, Cooper C, Walmsley SL, Hull MW, Martel-Laferrière V, Klein MB; Canadian Co-infection Cohort Study Investigators. Real-World Impact of Direct Acting Antiviral Therapy on Health-Related Quality of Life in HIV/Hepatitis C Co-Infected Individuals. J Viral Hepat. 2018 Dec;25(12):1507-1514.
McLinden T, Moodie EEM, Harper S, Hamelin A-M, Anema A, Aibibula W, Klein MB, Cox J. Injection drug use, food insecurity, and HIV-HCV co-infection: a longitudinal cohort analysis. AIDS Care. 2018 Oct;30(10):1322-1328.
Almeida-Brasil CC, Moodie EEM, McLinden T, Hamelin A-M, Walmsley SL, Rourke SB, Wong A, Klein MB, Cox J. Medication non-adherence, multi-tablet regimens, and food insecurity are key experiences in the pathway to incomplete HIV suppression. AIDS. 2018 Jun 19;32(10):1323-1332.
Lacombe K, Klein MB. The Rocky Road to viral hepatitis elimination: assuring access to antiviral therapy for ALL coinfected patients from low‐ to high‐income settings. J Int AIDS Soc. 2018 Apr;21(10049):e25073.
Golizeh M, Melendez-Pena CE, Ward BJ, Saeed S, Santamaria C, Conway B, Cooper C, Klein MB, Ndao M; Canadian Co-Infection Cohort (CTN222). Proteomic fingerprinting in HIV/HCV co-infection reveals serum biomarkers for the diagnosis of fibrosis staging. PLoS ONE. 2018 Apr 2;13(4):e0195148.
Sacks-Davis R, Doyle JS, Rauch A, Beguelin C, Pedrana AE, Matthews GV, Prins M, van der Valk M, Klein MB, Saeed S, Lacombe K, Chkhartishvili N, Altice FL, Hellard ME. Linkage and retention in HCV care for HIV-infected populations: early data from the DAA era. J Int AIDS Soc. 2018 Apr;21 Suppl 2(7):e25051.
Rossi C, Saeed S, Cox J, Vachon ML, Martel-Laferrière V, Walmsley SL, Cooper C, Gill MJ, Hull MW, Moodie EEM, Klein MB; Canadian Co-infection Cohort Investigators. Hepatitis C virus cure does not impact kidney function decline in HIV co-infected patients. AIDS. 2018 Jan 23 epub ahead of print.
Aibibula W, Cox J, Hamelin AM, Moodie EEM, Naimi AI, McLinden T, Klein MB, Brassard P; Canadian Co-infection Cohort Investigators. Impact of food Insecurity on depressive symptoms among HIV-HCV co-infected People. AIDS Behav. 2017 Dec;21(12):3464-72.
McLinden T, Moodie EEM, Hamelin AM, Harper S, Walmsley SL, Paradis G, Aibibula W, Klein MB, Cox J. Injection drug use, unemployment, and severe food insecurity among HIV-HCV Co-infected individuals: A mediation analysis. AIDS Behav. 2017 Dec;21(12):3496-505.
Moqueet N, Kanagaratham C, Gill MJ, Hull MW, Walmsley SL, Radzioch D, Saeed S, Platt RW, Klein MB; Canadian Co-infection Cohort Study (CTN 222). A prognostic model for development of significant liver fibrosis in HIV-hepatitis C co-infection. PLoS ONE. 2017 May 3;12(5):e0176282.
Young J, Rossi C, Gill J, Walmsley S, Cooper C, Cox J, Martel-Laferriere V, Conway B, Pick N, Vachon ML, Klein MB; Canadian Co-infection Cohort Investigators. Risk factors for hepatitis C virus reinfection after sustained virologic response in patients co-infected with HIV. Clin Infect Dis. 2017 Feb 12 [epub ahead of print].
Martel-Laferrière V, Nitulescu R, Cox J, Cooper C, Tyndall M, Rouleau D, Walmsley SL, Wong L, Klein MB; Canadian Co-infection Cohort Study Investigators. 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. BMC Infect Dis. 2017 Jan;17(1):80.
Gjærde LI, Shepherd L, Jablonowska E, Lazzarin A, Rougemont M, Darling K, Battegay M, Braun D, Martel-Laferrière V, Lundgren JD, Rockstroh JK, Gill J, Rauch A, Mocroft A, Klein MB, Peters L. 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. Clin Infect Dis. 2016 Sep;63(6):821-9.
Klein MB, Rockstroh JK, Wittkop L. Effect of coinfection with hepatitis C virus on survival of individuals with HIV-1 infection. Curr Opin HIV AIDS. 2016 Sep;11(5):521-6.
Kyle RP, Moodie EEM, Klein MB, Abrahamowicz M. Correcting for measurement error in time-varying covariates in marginal structural models. Am J Epidemiol. 2016 Aug;184(3):249-58.
Moqueet N, Cooper C, Hull MW, Gill J, Platt RW, Klein MB; Canadian Co-infection Cohort. Responder Interferon Lambda genotypes are associated with higher risk of liver fibrosis in HIV-hepatitis C virus co-infection. J Infect Dis. 2016 Jul;214(1):80-6.
Rossi C, Cox J, Cooper C, Martel-Laferrière V, Walmsley SL, Gill J, Sapir-Pichhadze R, Moodie EEM, Klein MB; Canadian Co-infection Cohort Investigators. Frequent injection cocaine use increases the risk of renal impairment among hepatitis C and HIV coinfected patients. AIDS. 2016 Jun;30(9):1403-11.
Young J, Mucsi I, Rollet-Kurhajec KC, Klein MB; Canadian Co-infection Cohort. Fibroblast growth factor 23: associations with antiretroviral therapy in patients co-infected with HIV and hepatitis C. HIV Med. 2016 May;17(5):373-9.
Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec KC, Pick N, Martel-Laferrière V, Hull MW, Gill MJ, Cox J, Cooper C, Klein MB; Canadian Co-Infection Cohort Study. How generalizable are the results from trials of direct antiviral agents to people coinfected with HIV/HCV in the real world? Clin Infect Dis. 2016 Apr;62(7):919-26.
Jenabian MA, Mehraj V, Costiniuk CT, Vyboh K, Kema I, Rollet K, Paulino Ramirez R, Klein MB, Routy JP. Influence of hepatitis C virus sustained virological response on immunosuppressive tryptophan catabolism in ART-treated HIV/HCV coinfected patients. J Acquir Immune Defic Syndr. 2016 Mar;71(3):254-262.
Costiniuk CT, Brunet L, Rollet-Kurhajec KC, Cooper CL, Walmsley SL, Gill MJ, Martel-Laferrière V, Klein MB. Tobacco smoking is not associated with accelerated liver disease in human immunodeficiency virus-hepatitis C coinfection: a longitudinal cohort analysis. Open Forum Infect Dis. 2016 Mar;3(2):ofw050.
Cox J, Hamelin AM, McLinden T, Moodie EEM, Anema A, Rollet-Kurhajec KC, Paradis G, Rourke SB, Walmsley SL, Klein MB, Canadian Co-infection Cohort Investigators. Food insecurity in HIV-hepatitis C virus co-infected individuals in canada: the importance of co-morbidities. AIDS Behav. 2016 Feb 24 [epub].
Brunet L, Moodie EEM, Young J, Cox J, Hull MW, Cooper C, Walmsley SL, Martel-Laferrière V, Rachlis A, Klein MB, Canadian Co-Infection Cohort Study. Progression of liver fibrosis and modern combination antiretroviral therapy regimens in HIV-hepatitis C-coinfected persons. Clin Infect Dis. 2016 Jan;62(2):242-9.
Brunet L, Moodie EEM, Cox J, Gill J, Cooper C, Walmsley SL, Rachlis A, Hull MW, Klein MB; Canadian Coinfection Cohort Study Investigators. Opioid use and risk of liver fibrosis in HIV/hepatitis C virus-coinfected patients in Canada. HIV Med. 2016 Jan;17(1):36-45.
Rollet-Kurhajec KC, Moodie EEM, Walmsley SL, Cooper C, Pick N, Klein MB; Canadian Co-infection Cohort Study (CTN 222). Hepatic fibrosis progression in HIV-hepatitis C virus co-infection – the effect of sex on risk of significant fibrosis measured by Aspartate-to-Platelet Ratio Index. PLoS ONE. 2015 Jun;10(6):e0129868.
Yeung MW, Young J, Moodie E, Rollet-Kurhajec KC, Schwartzman K, Greenaway C, Cooper C, Cox J, Gill J, Hull MW, Walmsley SL, Klein MB. Changes in quality of life, healthcare use, and substance use in HIV/hepatitis C coinfected patients after hepatitis C therapy: a prospective cohort study. HIV Clin Trials. 2015 May;16(3):100-10.
Moqueet N, Infante-Rivard C, Platt R, Young J, Cooper C, Hull MW, Walmsley SL, Klein MB; Canadian Co-Infection Cohort Study Investigators. Favourable IFNL3 genotypes are associated with spontaneous clearance and are differentially distributed in Aboriginals in Canadian HIV-hepatitis C co-infected individuals. IJMS. 2015 Mar;16(3):6496-512.
Saarela O, Stephens DA, Moodie EEM, Klein MB. On Bayesian estimation of marginal structural models. Biom. 2015 Jun;71(2):279-88.
Cooper C, Rollet-Kurhajec KC, Young J, Vasquez C, Tyndall M, Gill J, Pick N, Walmsley SL, Klein MB; Canadian Co-infection Cohort Study Investigators. HIV virological rebounds but not blips predict liver fibrosis progression in antiretroviral-treated HIV/hepatitis C virus-coinfected patients. HIV Med. 2015 Jan;16(1):24-31.
Klein MB, Rollet-Kurhajec KC, Moodie EEM, Yaphe S, Tyndall M, Walmsley SL, Gill J, Martel-Laferrière V, Cooper C; Canadian Co-infection Cohort Investigators. Mortality in HIV-hepatitis C co-infected patients in Canada compared to the general Canadian population (2003-2013). AIDS. 2014 Aug;28(13):1957-65.
Moodie EEM, Stephens DA, Klein MB. A marginal structural model for multiple‐outcome survival data: assessing the impact of injection drug use on several causes of death in the Canadian Co‐infection Cohort. Stat Med. 2014 Apr;33(8):1409-25.
Cox J, Maurais E, Hu L, Moodie EEM, Law S, Bozinoff N, Potter M, Rollet K, Hull MW, Tyndall M, Cooper C, Gill J, Saeed S, Klein MB; Canadian Co-infection Cohort (CTN 222). Correlates of drug use cessation among participants in the Canadian HIV-HCV Co-infection Cohort. Drug Alcohol Depend. 2014 Apr;137:121-8.
Schnitzer ME, Moodie EEM, van der Laan MJ, Platt RW, Klein MB. Modeling the impact of hepatitis C viral clearance on end‐stage liver disease in an HIV co‐infected cohort with targeted maximum likelihood estimation. Biometrics. 2014 Mar;70(1):144-152.
Brunet L, Moodie EEM, Rollet K, Cooper C, Walmsley SL, Potter M, Klein MB; Canadian Co-infection Cohort Investigators. Marijuana smoking does not accelerate progression of liver disease in HIV-hepatitis C coinfection: a longitudinal cohort analysis. Clin Infect Dis. 2013 Sep;57(5):663-670.
Young J, Potter M, Cox J, Cooper C, Gill J, Hull MW, Walmsley SL, Klein MB. Variation between Canadian centres in the uptake of treatment for hepatitis C by patients coinfected with HIV: a prospective cohort study. CMAJ Open. 2013;1(3):e106-14.
Hull MW, Rollet K, Klein MB, for the Canadian Co-infection Cohort Investigators. Reply to Mandorfer et al. Clin Infect Dis. 2013 Mar;56(6):905-6.
Klein MB, Rollet KC, Hull MW, Cooper C, Walmsley SL, Conway B, Pick N; Canadian Co-infection Cohort Study (CTN222) Investigators. Who needs direct-acting antivirals for HCV? Challenges faced in advancing HCV therapy for HIV-HCV-coinfected individuals. Antivir Ther. 2013;18(5):717-21.
Klein MB, Rollet KC, Saeed S, Cox J, Potter M, Cohen J, Conway B, Cooper C, Côté P, Gill J, Haase D, Haider S, Hull MW, Moodie E, Montaner J, Pick N, Rachlis A, Rouleau D, Sandre R, Tyndall M, Walmsley SL; Canadian HIV-HCV Cohort Investigators. HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for reducing preventable morbidity and mortality. HIV Med. 2013 Jan;14(1):10-20.
Hull MW, Rollet K, Moodie EEM, Walmsley SL, Cox J, Potter M, Cooper C, Pick N, Saeed S, Klein MB; Canadian Co-infection Cohort Study Investigators. Insulin resistance is associated with progression to hepatic fibrosis in a cohort of HIV/hepatitis C virus-coinfected patients. AIDS. 2012;26(14):1789-94.
Hull MW, Rollet K, Odueyungbo A, Saeed S, Potter M, Cox J, Cooper C, Gill J, Klein MB; Canadian Co-infection Cohort Investigators. Factors associated with discordance between absolute CD4 cell count and CD4 cell percentage in patients coinfected with HIV and hepatitis C virus. Clin Infect Dis. 2012 Jun;54(12):1798-805.
Thorpe J, Saeed S, Moodie EE, Klein MB; Canadian Co-infection Cohort Study (CTN222). Antiretroviral treatment interruption leads to progression of liver fibrosis in HIV-hepatitis C virus co-infection. AIDS. 2011 Apr;25(7):967-75.
Potter M, Odueyungbo A, Yang H, Saeed S, Klein MB. Impact of hepatitis C viral replication on CD4+ T-lymphocyte progression in HIV–HCV coinfection before and after antiretroviral therapy. AIDS. 2010 Jul;24(12):1857-65.
Rizza SA, Cummins NW, Rider DN, Saeed S, Klein MB, Badley AD. 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. AIDS. 2010 Nov;24(17):2639-44.
Klein MB, Saeed S, Yang H, Cohen J, Conway B, Cooper C, Côté P, Cox J, Gill J, Haase D, Haider S, Montaner J, Pick N, Rachlis A, Rouleau D, Sandre R, Tyndall M, Walmsley S. Cohort profile: the Canadian HIV-hepatitis C co-infection cohort study. Int J Epidemiol. 2010 Oct;39(5):1162-9.
Dr. John Gill
Southern Alberta Clinic, Calgary
Dr. Stephen Sanche
SHARE University of Saskatchewan, Saskatoon
Dr. Alexander Wong
Regina General Hospital, Regina
Dr. Neora Pick
Oak Tree Clinic, Vancouver
Dr. Brian Conway
PENDER Downtown Infectious Diseases Clinic, Vancouver
Dr. Aida Sadr
Native BC Health Center, St. Paul’s Hospital, Vancouver
Dr. Julio Montaner
BC Centre for Excellence in HIV/AIDS,St. Paul’s Hospital, Vancouver
Dr. Shariq Haider
McMaster University Medical Centre, Hamilton
Dr. Roger Sandre
The HAVEN/Hemophilia Program HRSRH, Sudbury
Dr. Sharon Walmsley
Toronto General Hospital, Infectious Disease Division, Toronto
Dr. Jeff Cohen
Windsor Regional Hospital, Windsor
Dr. Curtis Cooper
The Ottawa Hospital – General Campus, Ottawa
Dr. Marina Klein
Research Institute of McGill University Health Centre, Montreal
Dr. Danielle Rouleau
CHUM – Hôtel-Dieu, Montreal
Dr. Joseph Cox
Royal Victoria Hospital (former MCI), Montreal
Dr. Marie-Louise Vachon
CHU de Québec-Université Laval
Ph: 418-525-4444 ext 47778
Dr. Pierre Coté
Clinique Médicale du Quartier Latin, Montreal
Dr. Lisa Barrett
Queen Elizabeth II Health Sciences Centre, Halifax
If you would like more information on this clinical study, please refer to a participating site or visit the CTN 222 website at www.cocostudy.ca.
Dr. Marina Klein, Research Institute of McGill University Health Centre, Montreal, Ph: 514-843-2090