Centre Background

CCIBS was established in 1999 under the directorship of Professor Simon Mallal and Professor Ian James as a joint research centre of Murdoch University and RPH. Professor Mallal is a HIV physician, clinical immunologist and immunopathologist in the Department of Clinical Immunology and Biochemical Genetics (DCIBG) at RPH and Professor Ian James a senior academic in Mathematics and Statistics (Division of Science and Engineering) at Murdoch University. Their scientific collaboration began in 1993 when Professor Mallal was awarded a Commonwealth AIDS Research Grant (the NHMRC equivalent for HIV research at the time) and undertook studies as senior lecturer and senior research fellow at Murdoch University.

Professor Mallal had a longstanding involvement in HIV as a staff member of DCIBG since 1987, which has led clinical and laboratory services since the beginning of the HIV epidemic. Professor Mallal set up the WA HIV Cohort Study database and electronic networks collecting observational data for clinical care of patients attending these centres. The collection of comprehensive longitudinal, epidemiologic, clinical and laboratory data from a large 'captive' population in one geographic region remains unique in the world. Collaboration with Professor James brought high level statistics, including new methods, to analysis of this 'real-life' data and attracted high calibre PhD students and post-doctoral scientists to help conduct the research. Analyses were directed at determining the causes of novel drug toxicities emerging in the HIV clinic at that time. Work on this attracted international interest, including from GlaxoSmithKline who provided initial input funds to support expansion of the research.

CCIBS was founded with a view to securing ongoing financial support from other sources (including commercialisation of scientific innovations) and formally commenced activity under the terms of a mutually agreed memorandum of understanding. The original charter of the Centre was to foster interactions between scientists from different fields, clinicians and statisticians to solve problems currently facing HIV-infected patients in WA. The legacy of DCIBGs' internationally reputed immunogenetics capability, developed over 25 years, was also important. In particular 'tissue typing' or testing of human leukocyte antigens (HLA) - 'recognition' molecules in the immune response against infection - facilitated application of the novel Epipop technology at this time. Epipop was successfully patented by Professor Mallal and prior to formation of CCIBS, both Murdoch University and RPH agreed to formation of a spin-off company Epipop Ltd, which has since provided support for CCIBS. Drug toxicity, Epipop and HLA/HIV interactions formed the core areas of initial research. An early emphasis on collaboration and the clinical imperative has been very successful. Within five years of operations, CCIBS has grown to include 32 staff members working across five broad areas of research: HIV, HCV, drug hypersensitivity, long-term drug toxicities and biostatistical methods.

The Centre receives enormous and ongoing support of Western Australian HIV-infected patients, who are recognised as primary 'users of its outputs'. HIV-infected patients have participated in research since the early 1980s when HIV was associated with near universal progression to AIDS and death. Over the last 20 years, they have seen their strong support and advocacy for clinical trials and research and for the Immunodeficiency Foundation and CCIBS translate to improvements in clinical care. The Centre's history shows that its research objectives have always been firmly anchored to the needs of these 'users of its outputs' but these outputs have revealed great scope for applications beyond HIV.

Research Background

Human immunodeficiency virus (HIV) is a frequently mutating retrovirus that attacks the human immune system and which has been shown to cause acquired immune deficiency syndrome (AIDS). There are 43 million HIV-infected adults and children worldwide, and 13,000 people become infected with HIV every day, the majority in sub-Saharan Africa. In the absence of an effective vaccine, the HIV pandemic is the most devastating disease in human history and at the top of global health care priorities. In Western Australia, HIV-infected individuals have benefited from a CCIBS-generated statewide HIV clinical service that is second to none underpinned by world-class clinical research. Important scientific discoveries made by the CCIBS have directly advanced clinical care of HIV infected individuals in WA and around the world, attracting intense interest from the international community involved in global efforts against HIV.

Hepatitis C (HCV) is a form of hepatitis (liver inflammation) caused by a virus, and infects 170 million people worldwide. Acute hepatitis C infection has no symptoms and can become chronic, causing long-term damage to the liver. Approximately 40% of patients infected with HIV are also infected with the HCV, mainly because both viruses share the same routes of transmission.

Centre research relates to the overall theme of understanding interactions between adaptable pathogens, drugs and the human host at genetic, cellular and clinical levels. Work to date has been driven by advances in five broad research streams: HIV, HCV, drug hypersensitivity, metabolic drug toxicities, and biostatistical methods. The group's unique convergence of clinical patient care, experimental biology and innovation in statistics and computing has underpinned key scientific achievements, which are outlined in section 0.

A major clinical imperative driving the research activities of the Centre has been the need to investigate chronic toxicities observed in patients receiving long-term antiretroviral therapy for HIV infection. While this potent therapy has resulted in great clinical and survival benefit for patients with HIV infection and has in most cases outweighed the risk of short-term side effects, long-term complications have become a critical issue. 'Lipodystrophy syndrome' is the name given to a set of changes to blood lipids, glucose levels and body habitus. There is concern that as a result of these changes patients may be at risk of premature coronary artery disease and diabetes. Furthermore, changes in fat distribution, may be disfiguring and many patients are not able to retain their anonymity as HIV -infected individuals. Because of these concerns, adherence to therapy may be compromised.

Data derived from the participants of the Western Australian HIV Cohort Study is providing clinical information to aid identification of the causes of the side effects of antiretroviral therapy. Combining high quality clinical observational research and sophisticated statistical approaches provides important observations that will influence clinical practice and improve outcomes for patients, as well as powerfully informing basic science research within the group. The close interaction of health care workers, medical researchers and statisticians at the Centre has enabled studies to be designed to address the increasingly important area of chronic toxicity related to HIV treatment. These have allowed the Centre to refine and optimise drug treatment and identify predictors of responses to therapy. Moreover, these toxicities can be considered an "experiment of man" or "physiological probe" that have given CCIBS researchers many fundamental biological insights.

CCIBS now has five core areas of active research: HIV, HCV, drug hypersensitivity, long-term drug toxicity and biostatistical methods. The Centre's strengths in HIV medicine, molecular genetics and biostatistics have made possible novel contributions in these areas.