Non-AIDS co-morbidities

With the availability of combination antiretroviral therapy successful viral suppression is possible, leading to immensely improved life expectancies for people living with HIV. However, even if full viral suppression is achieved, there is still persistently ongoing immune system activation, which increases the risk of developing non-AIDS comorbidities, such as cardiovascular diseases and non-alcoholic fatty liver diseases. In addition, prevalence of psychiatric symptoms are higher in people living with HIV compared to the general population. Furthermore, with the COVID-19 pandemic running its course through the inclusion phase of the 2000HIV cohort presented an unprecedented opportunity to study the effects of COVID-19 infection, vaccination and lock-down events in this population.

Cardiovascular disease is now one of the leading causes of death in people living with HIV (PLHIV) under antiretroviral therapy. Moreover, PLHIV have an increased risk of developing cardiovascular disease compared to uninfected individuals. The exact pathophysiological mechanism behind the increased risk is unknown. We aim to discover underlying biological pathways for cardiovascular disease in PLHIV and biomarkers that predict future events.

At baseline, clinical information including medical history, smoking status and combination antiretroviral therapy use were obtained. All participants underwent carotid ultrasound for intima media measurements and plaque assessments, and an electrocardiogram was made. Cardiovascular risk profiles were constructed with Framingham Risk Score and SCORE2/SCORE2-OP.

All participants will be followed up for 2-5 years whereby all clinical information and cardiovascular events will be available as well as follow-up electrocardiogram measurements and blood collection at 2 years. In depth multi-omics characterization, with plasma proteomics, (lipo)metabolomics, bulk transcriptomics, genomics, epigenomics and metagenomics will be performed to link these measurements with carotid atherosclerosis, cardiovascular disease at baseline and incident cardiovascular disease with use of follow up data.

At baseline, 9.1% of participants had a history of cardiovascular disease and we expect that 5-7% of individuals will develop an event during the 2- to 5-year follow-up period.