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HIV-1 infection is characterised by high levels of virus replication and a progressive loss of immune cells, particularly CD4+ T lymphocytes. Highly active antiretrovial therapy (HAART) for HIV-1 infection results in profound suppression of viral replication, a substantial increase in CD4+ T lymphocytes and a decrease in morbidity and mortality. The primary source of T lymphocytes in early human development is the thymus. Recently, it has been demonstrated that the thymus remains functional thro ....HIV-1 infection is characterised by high levels of virus replication and a progressive loss of immune cells, particularly CD4+ T lymphocytes. Highly active antiretrovial therapy (HAART) for HIV-1 infection results in profound suppression of viral replication, a substantial increase in CD4+ T lymphocytes and a decrease in morbidity and mortality. The primary source of T lymphocytes in early human development is the thymus. Recently, it has been demonstrated that the thymus remains functional throughout adult life. The role of the thymus in HIV-1 infection remains controversial. Studies of the role of the thymus in HIV-1-infected individuals has been limited by the lack of a marker of thymic function in vivo. We have recently developed a novel assay to quantify cells of recent thymic origin by taking advantage of certain molecular events that occur in the thymus during the production of new T lymphocytes. This molecular event creates a circular piece of DNA, called a T-cell receptor excision circles (TREC). TREC concentration in the periphery will increase with an increase in thymic output but will reduce in the presence of T cell proliferation or cell death. In order to determine the contribution of the thymus to immune reconstitution following HAART, we plan to study the dynamics of thymus function in HIV-1 infection by measuring TREC and T cell turnover in HIV-1 infection prior to and following HAART. In a subgroup of individuals, more commonly seen following treatment of HIV-1 infection in children, there is an increase in CD4+ T lymphocytes in the absence of a significant reduction in viral suppression. The role of the thymus in this unique subset of individuals will be studied.Read moreRead less
Understanding The Establishment Of HIV Reservoirs And Development Of HIV Eradication Strategies
Funder
National Health and Medical Research Council
Funding Amount
$380,891.00
Summary
Understanding why, when, how and at what pace the HIV virus hides and establishes itself in one's body will allow us to design new ways for preventing and eliminating this reservoir of hidden HIV. As a clinician scientist in HIV and infectious diseases, I will drive clinical studies to explore the kinetics of HIV in patients who recently acquired HIV, those who start HIV treatment early, and those chronically infected with HIV so as to investigate novel means to minimise HIV hiding spots.
Translating Research Into HIV-related Health Outcomes In The Developing World
Funder
National Health and Medical Research Council
Funding Amount
$714,745.00
Summary
Professor Crowe's research addresses important health issues for HIV infected people living in resource limited countries. Her team validates low cost point of care tests to monitor HIV infection, including a test she co-developed to determine when to start anti-HIV treatment, and investigates how these low cost tests can improve clinical care of people with HIV and TB. In addition she will determine how changes in the immune system increase the risk of heart attacks in young HIV patients.
Hepatitis C affects between 1-3% of Australians. Currently, there is no effective vaccine and only 30% will spontaneously clear infection, while the remained develop a chronic disease with a small risk of progression to liver cirrhosis and liver cancer over time. This study aims to evaluate the safety and efficacy of a two different treatment regimens among individuals with recent Hepatitis C infection; and define the risk factors and natural history of Hepatitis C superinfection during treatmen ....Hepatitis C affects between 1-3% of Australians. Currently, there is no effective vaccine and only 30% will spontaneously clear infection, while the remained develop a chronic disease with a small risk of progression to liver cirrhosis and liver cancer over time. This study aims to evaluate the safety and efficacy of a two different treatment regimens among individuals with recent Hepatitis C infection; and define the risk factors and natural history of Hepatitis C superinfection during treatment.Read moreRead less
The development of cures, vaccines and better treatments for HIV/AIDS is an urgent global health priority. This team of seven groups in Sydney and Melbourne will study how HIV can lie dormant in some parts of the body, evading eradication by HIV therapy, as well as how the immune system responds to the virus. This will allow for design of novel vaccines and treatments. The researchers have skills in basic virology and immunology, and translating laboratory findings into human clinical trials.
Randomised Trial To Determine The Safety And Efficacy Of Early Vs Deferred Treatment Of HIV
Funder
National Health and Medical Research Council
Funding Amount
$1,070,331.00
Summary
Treatments for HIV represent a miraculous achievement of medical research. Global use of antiretroviral drugs has prevented substantial morbidity and mortality. However, it is unclear if these drugs should be used in people who are HIV positive with early HIV disease but no clinical symptoms. The START trial will result in a precise estimate of the risk-benefit for earlier versus later use of these treatments. It will immediately affect treatment guidelines around the world and inform future res ....Treatments for HIV represent a miraculous achievement of medical research. Global use of antiretroviral drugs has prevented substantial morbidity and mortality. However, it is unclear if these drugs should be used in people who are HIV positive with early HIV disease but no clinical symptoms. The START trial will result in a precise estimate of the risk-benefit for earlier versus later use of these treatments. It will immediately affect treatment guidelines around the world and inform future research for many years to come.Read moreRead less
The Primary HIV Combined United Database (PCUD) is the largest database of patients with primary HIV infection in Australia. Dating back to 1983, it collects data from people with HIV seroconversion. Primary HIV infection, or seroconversion provides a unique opportunity to study HIV throughout its natural history. This study aims to link data on long term health outcomes such as AIDS, cancer and cardiovascular disease in this cohort, which can then be used to understand the determinants of progr ....The Primary HIV Combined United Database (PCUD) is the largest database of patients with primary HIV infection in Australia. Dating back to 1983, it collects data from people with HIV seroconversion. Primary HIV infection, or seroconversion provides a unique opportunity to study HIV throughout its natural history. This study aims to link data on long term health outcomes such as AIDS, cancer and cardiovascular disease in this cohort, which can then be used to understand the determinants of progression and complications of HIV infection.Read moreRead less
A Randomised Trial To Compare Dolutegravir+darunavir/r Versus Recommended Standard Of Care Antiretroviral Regimens In Patients With HIV Infection Who Have Failed Recommended First Line Therapy
Funder
National Health and Medical Research Council
Funding Amount
$2,323,209.00
Summary
Public sector programs for provision of antiretroviral drugs in developing countries need regimens of therapy that are safe, effective and simple to administer. The evidence base to support first line therapy is strong. This contrasts with a relative paucity of evidence for second regimens of therapy once first line effectiveness has been lost. This trial will address that evidential deficit and support evidence-based recommendations for global health.
Enhancing The Cascade Of HIV Care To Maximise The Prevention Benefits Of Antiretroviral Therapy For Populations Living With HIV
Funder
National Health and Medical Research Council
Funding Amount
$344,644.00
Summary
Antiretroviral drugs are effective at preventing death and illness for populations with HIV and preventing HIV transmission. I will undertake a series of studies to measure the impact of current antiretroviral treatment to prevent both illness and new infections in Australia. I will also undertake a series of studies to increase HIV testing, diagnose HIV earlier, and improve people’s linkage and retention HIV in care and evaluate the impact of these interventions on HIV transmission.
The Pharmacokinetic, Pharmacodynamic And Pharmacogenomic Outcomes Of Reduced Dosage Of Efavirenz: The Encore1 Study
Funder
National Health and Medical Research Council
Funding Amount
$1,234,943.00
Summary
Our primary aim is to assess blood concentrations of a drug called efavirenz, an important drug used in the treatment of HIV infection and associate these with variability of genes that control metabolism of the drug. A better understanding of gene variability and how it relates to safety and efficacy outcomes at a reduced, compared to a standard dose of efavirenz could support improved treatment of HIV disease.