Deep inside HIV:
the multi-omics approach

16 februari 2023

Not all people living with HIV are the same, even when this chronic virus is undetectable through medication. HIV medication has ensured that people living with HIV are becoming older. The long-term effects of the virus are also becoming more noticeable,however, as they are at higher risk for cancer, cardiovascular-, and hepatic disease. The excess risk for these comorbidities compared to the general population remains unexplained. In addition, the HIV population is very heterogeneous; ranging from people who develop severe disease shortly after contracting HIV, to people who are protected as they are capable to spontaneously control the virus themselves (known as ‘elite controllers’). The 2000HIV study uses a so called ‘multi-omics strategy’ where homeostatic systems of the body are viewed at the molecular level, to fully understand these phenomena.

As part of the Human Functional Genomics Project, four clinical researchers build a cohort of 1895 PLHIV attending HIV clinics at Radboudumc (Nijmegen), OLVG (Amsterdam), Erasmusmc (Rotterdam) and ETZ (Tilburg), the Netherlands. They collected blood for extensive measurements, performed liver steatosis and fibrosis measurements using FibroScan and assessed signs of subclinical cardiovascular disease in the carotid artery. The 2000HIV research group, that includes academic researchers from the Netherlands, Belgium, Germany, Austria as well as researchers from VIIV Healthcare from United Kingdom and United States of America now publishes the extensive methods they will use and provide an overview of the cohort in Frontiers in Immunology.

In the near future, this research group will look at the molecular level to different processes in the body. Research will focus on ‘genomic’ (genetics), ‘epigenomics’ (epigenetics), ‘transcriptomics’ (RNA levels), ‘proteomics’ (proteins in plasma), ‘metagenomics’ (bacteria living in the mouth and gut), ‘immunophenotyping’ (phenotype of immune cells) and cytokine production capacity of the immune system. By connecting and integrating results they are attempting to understand how the course of a HIV infection differs between people living with HIV. ‘What mechanisms are responsible for the increase in cardiovascular disease?’, ‘Are people living with HIV biologically older?’, and ‘Which factors play a role in elite controllers and not in others?’ are some of the central research questions. In addition, they managed to collect data of people throughout the first two years of the COVID pandemic, offering possibilities to coincidentally answer relevant questions, like: ‘Is our immune system affected by lockdowns?’.