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There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this proj ....There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this project is to investigate the liver disease caused by HBV in co-infected patients and the development of antiviral resistance due to the long-term treatment with lamivudine. We will develop a data base to monitor virological, biochemical and histological parameters for each of these co-infected patients. We will collate all information on these patients that are attending these various centres. This data base will be essential for monitoring the disease in patients with a poor immune system versus patients with a normal immune system. The HBV virus isolated from these patients will be characterised by sequence analysis. The sequence analysis of these viruses will be compared before and after treatment to determine any resistance markers that have developed. These resistant markers will be copied into an infectious clone using specialised molecular techniques. Clones containing these resistant markers will be analysed in the laboratory to determine the antiviral sensitivity to lamivudine and a number of new drugs against hepatitis B virus. This information will be important in treating patients that are co-infected with HBV and HIV and have already developed resistance to lamivudine.Read moreRead less
Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients ....Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients with chronic infection are expected to die prematurely due to chronic liver disease or primary liver cancer. Interestingly, exposure to HBV can lead to either acute resolving or chronic HBV infection. Like chronic infections, acute infections involve spread of virus to virtually every hepatocyte, followed by rapid clearance of the virus mediated by the host immune response. Our immediate aim is to study the resolution of acute HBV infections to determine how the stable intracellular viral genome, covalently closed circular DNA (cccDNA), is cleared from the nucleus of infected hepatocytes. Our broad long-term aim is to develop new and effective treatments for chronic HBV infection based on a better understanding of how acute HBV infections are resolved by the host. Based on our previous work we believe that clearance of cccDNA requires hepatocyte death, together with compensatory proliferation of other infected hepatocytes. We will perform detailed studies in duck hepatitis B virus (DHBV) infected ducks to determine if hepatocyte death and compensatory proliferation are essential to clear the infection, or if mechanisms exist for clearance that do not involve cell destruction.Read moreRead less