Award Title: Prevalence of cytomeglaovirus and Epstein Barr virus and associated immune-activation and inflammation in adolescents with perinatally-acquired HIV.
Funder: The Academy of Medical Sciences

Abstract: In HIV-infected adults there is evidence of association between cytomegalovirus (CMV) or Epstein-Barr virus (EBV) co-infection with increased inflammation and reduced correlates of immunological health. In turn these co-infections have also been associated with non-AIDS events such as malignancies, cardiovascular or neurocognitive disease. It is known that HIV-infected adolescents have an increased risk of co-morbidities including malignancy compared to their HIV-uninfected peers, however the potential relationship between chronic co-infection with CMV or EBV and associated increased risk of these co-morbidities is not well-described. 

This study aims to quantify the presence of CMV and EBV in adolescents with perinatally-acquired HIV, and assess for correlates of immune-activation, dysregulation and inflammation that may be associated with non-AIDS diseases including malignancy. Blood samples will be taken from 130 adolescents from the largest tertiary centre, perinatally-acquired HIV clinic in the UK. These adolescents are under lifelong follow-up with more than 81% on suppressive antiretroviral therapy and are very well-characterised as the majority of attendees have been patients since infancy. Routine blood tests will assess HIV control and we will measure CMV and EBV alongside markers of inflammation. Flow-cytometry assays will quantify immune-activation, naïve and memory subsets, proliferation, degranulation and immune-regulation; and Luminex will measure a bespoke immune-oncology panel of proinflammatory cytokines and biomarkers associated with cancer, neurodegenerative or cardiovascular disease. Should the association between HIV co-infection with CMV or EBV be demonstrated to increase the risk for malignancy and other co-morbidities, a therapeutic trial examining treatment of co-infections or anti-inflammatory therapy would be warranted.

Lay Abstract: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are common viral infections that tend to causes relatively mild illness in healthy children and adults. However CMV can cause devastating disease in babies who are infected while they are developing during pregnancy and children who have problems with their immune systems, and EBV is known to increase the risk for some types of cancer. These viruses can cause long-term, chronic infection in children with an underlying condition that compromises the ability to fight infection such as Human Immunodeficiency Virus (HIV). It is known that young people with HIV have a 15-fold increased risk of cancer and other diseases affected the heart or brain compared to their HIV-uninfected peers, and so in this study we aim to explore whether having CMV or EBV might increase the chances of these young people developing cancer or other diseases.

This study will determine how common CMV and EBV infections are in a group of 130 individuals aged 15-33 years from the largest clinic for young people with HIV in the UK. Using blood tests we will then examine how the body responds to these chronic infections by measuring markers of inflammation and activation, and further explore whether these markers are associated with developing cancer or other diseases. This information will help inform doctors whether new treatment approaches are needed to treat chronic infection with CMV or EBV in these young people.

Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health Categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH