Overview

By understanding the causes of persistent immune activation and chronic inflammation in HIV patients, we aim to develop prognostic tools and adjunctive therapies to predict and improve health outcomes.

HIV infection is a chronic viral infection which can be managed using combination antiretroviral therapy such that progression to AIDS is greatly minimised. Long term management of patients receiving antiretroviral therapy, especially their risk of non-AIDS co-morbidities, is a major concern.

Our group focuses on understanding the immune defects that persist in HIV+ patients receiving combination antiretroviral therapy, and how these contribute to decreased life expectancy and increased non-AIDS co-morbidities such as cardiovascular disease.

By understanding the causes of persistent immune activation and chronic inflammation in HIV patients, we aim to develop prognostic tools and adjunctive therapies to predict and improve health outcomes.

We study cells of the innate immune system (monocytes and natural killer cells) that are important to inflammation.

Objectives

• To understand the causes of immune activation and inflammation remaining in HIV patients with virologic suppression on antiretroviral drugs
• To understand the mechanism of increased risk of cardiovascular disease in HIV+ patients
• To determine how inflammation alters natural killer cell signaling and function
• To understand the role of monocytes in malaria immunity.

Highlights

• Demonstration of persistent natural killer cell activation in virologically suppressed HIV patients
• Demonstration that monocyte phenotypic and functional changes in HIV patients mirror those seen during normal, healthy ageing
• Development of an in vitro model to study the differentiation of monocytes into foam cells and their role in atherosclerotic plaque formation
• Determination of signaling pathways required for cytokine responses to chondroitin sulphate binding P. falciparum malaria strains and the effect of HIV infection on these.

Projects

• Antimicrobial and immune modulatory effects of vaginal microbiota metabolites
  Determining the role of vaginal microbiota metabolites in activating HIV and other STIs.
• Getting to the heart of cardiovascular disease in HIV
  Investigating the pathogenesis of cardiovascular disease in HIV infection and identifying clinically useful predictors and therapies.
• Impact of a vaginal microbiota metabolite on epithelium integrity and HIV susceptibility
  Determining the role of a vaginal microbiota metabolite in enhancing the mucosal barrier to prevent HIV transmission.
• Targeting HIV-infected macrophages to achieve an HIV cure
  Optimising methods to target and kill HIV-infected macrophages using Natural Killer cells.
• The impact of viral infections on immune ageing.
  Characterising the impact of chronic and acute viral infections on immune ageing, immune dysfunction, and development of age-related diseases.
• The role of monocytes in the development of cardiovascular disease
  Examining how monocytes drive the thickening of the artery wall.