Despite effective therapy that suppresses HIV replication and prevents AIDS, people with HIV have double the risk of a number of co-morbid conditions including heart disease. Cytomegalovirus (CMV) is a herpesvirus, widespread in the community, which produces a typically asymptomatic infection in healthy individuals but establishes a lifelong, chronic infection in those whom it infects that demands substantial immune resources to control. CMV is a key driver of immune ageing and senescence and can collude with other viruses to drive chronic inflammation and immune dysfunction, leading to disease such as heart disease. As part of its strategy to evade the immune system, CMV expresses numerous proteins that mimic human immunomodulatory factors affecting how the immune systems responds to other pathogens. We hypothesize that HIV infection reactivates CMV in people with HIV, causing inflammation and immune damage, and that this reactivation is not fully reversed by anti-HIV therapy. This reactivation may also increase the production of immunomodulatory proteins by CMV which could be contributing to persistent immune dysfunction in people with HIV. Therefore, this project will explore the following questions: 1) Is there evidence of increased CMV reactivation in people with HIV? 2) Do people with HIV have higher levels of CMV immunomodulatory proteins and, if so, are they contributing to heightened inflammation? 3) Does CMV contribute to increased risk of heart disease in people with HIV? To address this, we will be collaborating with clinicians at the Alfred Hospital and utlilsing a unique bank of stored plasma samples from people with HIV with heart disease. This study is important to understand not only how CMV may be potentiating the effects of HIV, and thus whether treating CMV may be a beneficial adjunct to antiretroviral therapy, but many also uncover mechanisms relevant for infection with other pathogens and indeed immune aging in general. This project involves a range of laboratory techniques (ie ELISA, cytokine measurements, cell culture, molecular biology), data analysis/statistics and clinical research.
HIV, cytomegalovirus, immunology, virology, ageing, heart disease, inflammation, clinical research
Masters by research
Top-up scholarship funding available