CTN 326: LIVEHIV Cohort Plus

About the Study

CTN 326 will expand the existing LIVEHIV Cohort, already one of the worlds largest cohorts focused on fatty liver in people living with HIV. The expanded cohort will collect information over a 4-year period across four different sites in Canada to understand the risk of advanced chronic kidney disease (ACLD) in people living with HIV. The study aims to understand the contribution of non-alcoholic fatty liver diseases to advanced chronic liver disease (ACLD), which may be more common in people living with HIV. CTN 326 will develop a risk assessment tool to understand which individuals are at highest risk of developing ACLD. This study is informed by previous CTN pilot studies that investigated fatty liver in people living with HIV.

Background

With the success of antiretroviral therapies (ART), more than half of people living with HIV in Canada are now over the age of 50. As a result, there has been a significant increase in aging-related conditions in this group, some of which are also affected by HIV and ART. One such disease is ACLD (formerly referred to as cirrhosis), which has rapidly increased in recent years in both the general population and people living with HIV; mortality from ACLD has now surpassed cardiovascular disease and is second only to AIDS-related mortality in people living with HIV. Liver transplant is the only curative treatment of ACLD, which may be inaccessible to many people living with HIV. This means that it is vital to understand who is at greatest risk in order to prevent further progression.

In the general population, non-alcoholic fatty liver diseases (NAFLD; fatty buildup in the liver) is understood to be a main contributor to the development of ACLD. In people living with HIV, NAFLD may be twice as common compared to the general population, but its contribution to ACLD risk is not fully understood. In the past, hepatitis C virus (HCV) was a leading cause of NAFLD in the HIV-positive population, but now that HCV cure is possible, metabolic disorders like diabetes and excess weight are playing a larger role. People living with HIV have higher rates of diabetes, dyslipidemia, and hypertension compared with the general population; however, there are also HIV-specific risk factors such as use of older ART and high viral load during treatment interruption that may increase liver disease risk.

The lack of knowledge about ACLD and the role of NAFLD in people living with HIV is due to the complex interaction of the factors that affect liver health. CTN 326 aims to untangle this complexity, determine how NAFLD contributes to ACLD, and develop tools to identify those at greatest risk.