CTN 222: Canadian co-infection cohort

Background

Hepatitis C is an infection caused by the hepatitis C virus (HCV). The virus leads to inflammation and damage to the liver. HCV can be contracted through the same routes as HIV (mostly blood-to-blood contact or sexual contact). It is estimated that 20–30% of Canadians living with HIV also have HCV. Coinfection with HIV increases HCV viral replication and accelerates the progression of liver disease. In Canada, there are approximately 214,000 Canadians living with HCV, 70,900 Canadians living with HIV, and 14–21,000 Canadians living with both HCV and HIV. HIV–HCV co-infection is a major public health concern that disproportionately affects social and structurally vulnerable populations. This includes individuals facing poverty, unstable housing, substance use, stigma, discrimination, and barriers to accessing healthcare.

Research using cohort data has evolved from studying liver disease progression to the success rates and uptake of new DAA treatments, and to the risk of re-infection. The next phase of our research is to understand the long-term health consequences of a past HCV infection, including the risk of steatotic liver disease, diabetes, and cardiovascular disease. As people living with HIV age, these comorbidities are far more prevalent than in the general population. There is evidence that a prior HCV infection results in permanent immunologic damage and this may increase comorbidity risks for those with a past HCV infection. An increased risk would imply those with a past HCV infection need early or more frequent fatty liver disease monitoring, diabetes screening, and primary CVD prevention than is currently recommended for those living with HIV.

Study Approach

CTN 222 is a long-term observational cohort study and its participants are a diverse group of people linked to care including men who have sex with men (MSM), current and ex-injection drug users, Indigenous peoples, and women. Our participants are similar to those found in Canadian population studies of those with HIV and HCV (the BC Hepatitis Testers Cohort and PHAC I-Track surveys).

All eligible individuals who visit a cohort clinic are invited to participate in the study. Those enrolled are seen every 6 months at follow-up visits linked to their routine clinical care during which they complete a questionnaire, undergo a liver fibroscan, and provide clinical and research blood samples. Sociodemographic, behavioural and clinical data are collected, including information on diagnoses, HIV and HCV treatment, and care received.

Results

Since its inception, CTN 222 has led to 97 peer-reviewed publications: 23 papers published before 2015, 27 papers published between 2015 and 2019, and 47 papers published since 2020. The cohort has evolved from studies of disease progression and treatment outcomes to research on HCV elimination and long-term health. This sustained output has made the cohort an internationally recognized platform for understanding HIV–HCV coinfection and informing clinical care and policy.

Before 2015, our research focused on defining the natural history of HIV–HCV coinfection. Major themes included liver fibrosis progression, mortality, immune dysfunction, treatment outcomes with interferon-based therapies, genetic and immunological determinants of disease, and the impact of antiretroviral therapy on liver-related health. From 2015–2020, the research program evolved to address the transition to DAA therapy. Investigators evaluated treatment uptake, barriers to treatment, quality of life, reinfection, mortality trends, and the effects of policy changes on treatment access. During this period, the cohort also became a leading source of evidence on social determinants of health, including food insecurity, incarceration, substance use, and depression.

Since 2020, research has increasingly focused on HCV elimination, engagement in care, transmission risk, long-term outcomes after cure, hepatic steatosis, use of health services, overdose mortality, and mental health. New studies have examined COVID-19, virtual care, vaccine responses, and progress toward national elimination goals, while continuing to identify gaps in prevention and care among priority populations.

The cohort has also made important contributions to epidemiological and statistical methodology. Investigators have developed and applied dynamic treatment regime models, Bayesian and semiparametric causal inference methods, measurement error correction techniques, and methods for evaluating health policy interventions. These methodological studies have influenced research beyond HIV and viral hepatitis.

The cohort is used as a platform for other studies. These have included a study on food insecurity (CTN 264) and interventional trials at cohort sites – on citalopram as a treatment for depression (CTN 194), raltegravir as an alternative to protease inhibitors in HIV treatment (CTN 260), and switching to a single tablet treatment for HIV to improve treatment adherence (CTN 286).

Additional Information

You can contact the CTN 222 team via email at cviscoco@gmail.com and on X at our handle @cocostudy.