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The Future Of HIV Care - Long Term Remission And Eliminating Co-morbidities
Funder
National Health and Medical Research Council
Funding Amount
$577,189.00
Summary
Despite the great successes in antiretroviral therapy (ART) in reducing HIV-associated mortality, treatment is life long and there is no cure. The major barrier to a cure for HIV is the persistence of long lived latently infected cells on ART. Over the next five years I will discover, develop, optimise and evaluate novel interventions to eliminate latently infected cells, long lived infected cells in the liver and enhance HIV-specific immunity through immunotherapy.
We plan to continue our work that to date is consistent with the idea that excessive induction of the enzyme iNOS, and thus production of nitric oxide in key locations, is a central event in how falciparum malaria kills people who become infected with this parasite. This will largely be based on detecting iNOS and nitrotyrosine in tissues from autopsies collected as part of a malaria research programme conducted in Malawi. Laboratory experiments will also be performed. In particular, there is a ....We plan to continue our work that to date is consistent with the idea that excessive induction of the enzyme iNOS, and thus production of nitric oxide in key locations, is a central event in how falciparum malaria kills people who become infected with this parasite. This will largely be based on detecting iNOS and nitrotyrosine in tissues from autopsies collected as part of a malaria research programme conducted in Malawi. Laboratory experiments will also be performed. In particular, there is a body of evidence that suggests the following interactions between inflammatory cytokines and salicylate, with important practical ramifications, in children. 1. Salicylate toxicity, like the acute multi-organ form of childhood malaria it mimics, is probably caused by excess systemic iNOS induction. This plausibly includes the metabolic acidosis, hypoglycaemia, seizures, coma and cerebral oedema seen in both conditions. Both are thus logically susceptible to treatment with specific iNOS inhibitors. 2. The same picture would arise in children when smaller doses of salicylate synergise with IFN-g, IL-1b, and perhaps other cytokines induced by malaria as well as by viruses. This gives the first proposed explanation for Reye's syndrome, defining the circumstances in which it occurs, and predicting a rationale for its treatment. Through the parallels seen in different age groups in malaria and aspirin toxicity, it also rationalises the difference in childhood vs adult malaria syndromes. 3. The overall severity and mortality of childhood malaria in East Africa may be worsened, through this cytokine-salicylate synergy, by home treatment with aspirin when children first become ill. 4. A relative absence of salicylate intake by children in various malarial Pacific Islands may contribute to falciparum malaria being a less severe disease there than in East Africa.Read moreRead less
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.
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
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.
Identification And Quantification Of HIV Latency Biomarkers In The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$814,618.00
Summary
One major obstacle in curing HIV is the brain’s role as a potential reservoir of HIV infection. It is unknown if “reawakening” of HIV may lead to uncontrollable brain damage given that current antiretroviral drugs vary in their ability to treat brain infection. Not all patients have HIV brain infection so eradication therapies in themselves may be safe. We aim to identify and quantify biomarkers of HIV latency in the brain to stratify patients into these two cohorts.
Understanding And Preventing Chronic Disease In People Living With HIV
Funder
National Health and Medical Research Council
Funding Amount
$367,946.00
Summary
Australia’s ageing population is increasingly at risk of chronic diseases such as heart disease and diabetes. For Australians who are living with HIV, these diseases occur more frequently and at an earlier age. I will be investigating the underlying reasons for this increase in risk and will test innovative online systems that help people living with HIV reduce their risk of chronic disease. This work will provide important information for Australians at risk of developing chronic disease.
Escape And Reversion Of Critical Immune Responses: Insights Into Effective Immunity To HIV
Funder
National Health and Medical Research Council
Funding Amount
$372,446.00
Summary
The HIV pandemic is a global emergency. The overall goal of this grant proposal is to elucidate the requirements for protective immunity to HIV. Although immune responses have some effect on HIV replication, the virus mutates and evolves to escape immune pressure. However, each mutation away from wild-type virus likely results in at least some impairment in the ability of the virus to replicate. Where efficient immune responses target regions of the virus that are critical to virus replication, ....The HIV pandemic is a global emergency. The overall goal of this grant proposal is to elucidate the requirements for protective immunity to HIV. Although immune responses have some effect on HIV replication, the virus mutates and evolves to escape immune pressure. However, each mutation away from wild-type virus likely results in at least some impairment in the ability of the virus to replicate. Where efficient immune responses target regions of the virus that are critical to virus replication, escape mutations may result in viral variants incapable of causing disease. Resulting from an exciting collaboration between HIV and theoretical biologists, we have recently identified techniques to calculate the effectiveness of immunity and the cost of subsequent immune escape variants. We will use and expand these techniques to identify immune responses that result in the most effective control of viral replication. These studies will lead to ways to improve HIV vaccines and thereby prevent HIV.Read moreRead less