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Microbiology Australia Microbiology Australia
Issue 2

AIDS

Vertical Transmission

Welcome to this issue of Microbiology Australia, which focuses on the ongoing challenges of the AIDS pandemic and is timed to coincide with the 20th International AIDS Conference to be held this year in Melbourne in July. A wide range of topics from leaders in the field have been brought together by the guest editors Johnson Mak and Stephen Kent, and so this issue presents a current state-of-play with regards the challenges and progress in combating this deadly disease.

HIV

It has been nearly three decades since the discovery of human immunodeficiency virus type 1 (HIV-1). The collective global research efforts on HIV-1 in the past 30 years have drastically changed HIV-1 infection from a previous 'death sentence' to a manageable clinical condition – providing adequate access of anti-retroviral therapy is available. Throughout this period, along with their colleagues around the globe, Australian researchers have made significant contributions to HIV-1 research in a number of areas, including but not limit...

Challenges, progress and strategies in the search for a cure for HIV

The past three decades has seen a major transformation in the understanding and management of HIV infection. Effective combination antiretroviral therapy (cART) has transformed HIV from a universal death sentence to a chronic manageable disease. Current cART regimens are simpler - often only a single daily (combination) pill, but treatment must be taken life-long. Life expectancy of an HIV-infected person who receives effective cART, is now similar to a person without HIV1. The cost of long-term treatment is significant. There is now...

Antiretroviral therapy: research, rollout and resistance

Antiretroviral therapy has revolutionised the management of human immunodeficiency virus (HIV). Advances in research leading to the development of combination antiretroviral therapies (ARTs) have led to significant decreases in AIDS related morbidity and increases in life expectancy for individuals with access to treatment. The goal of ‘getting to zero:zero AIDs related deaths' now is within reach. Globally nearly 10million people have access to ART; however, further rollout efforts are required to reach the 34million people living with ...

HIV, hepatitis viruses and viral STIs: intertwined fates?

Although the major target cell for HIV in the body is the CD4 lymphocyte, uptake by and infection of other target cells such macrophages and dendritic cells also play a major role in pathogenesis. Macrophages are a major reservoir for HIV in most lymphoid tissue in the untreated patient and remain the major target cell in brain whether the subject is treated or not. Dendritic cells play a major role in transferring HIV efficiently to T cells particularly after viral entry through sexual transmission. Our work has focused on understanding how HI...

Moving towards HIV treatment as prevention

HIV prevention has entered a new and exciting era. In lieu of discovering an HIV cure or developing an effective vaccine, ‘combination prevention' is likely to underpin HIV prevention globally over coming decades1. Within the combination prevention framework, the concept of treatment as prevention (TasP) is attracting the most enthusiasm2.

Protecting the heart after HAART; understanding the pathogenesis of cardiovascular disease in people living with HIV

Advances in the management of HIV and antiretroviral therapy (ART) have led to substantial improvements in disease-free survival for patients with HIV. Life-expectancy is approaching that of the general population. Yet these gains have been tempered by increasing rates of non-AIDS-related co-morbidities. In fact the major burden of illness, health care utilization and premature death in HIV positive patients is now due to diseases of ageing. Cardiovascular disease (CVD) occurs at two times the rate in the general population and is a cause of si...

Therapeutic vaccination in HIV infection

The concept of using a vaccine to induce or enhance HIV-specific immune responses in those with established HIV infection has been through alternating waves of enthusiasm and skepticism over the past three decades of the HIV epidemic. The earliest therapeutic vaccination trials were conducted in subjects with uncontrolled viremia or suboptimal therapy and the highly activated and dysfunctional immune environment of such individuals would significantly impede the efficacy of any immunostimulatory approaches. Contemporary antiretroviral treatment...

A spectrum of (avoidable) HIV latency?

Long-lived latently HIV-infected cells present a major barrier to the eradication of the virus under ART. Current strategies are aimed at eliminating this reservoir of cells once it is established. However, it may be easier to prevent the formation of the reservoir rather than eliminate it.

Immune reconstitution disorders in HIV patients receiving antiretroviral therapy

Suppression of HIV infection by antiretroviral therapy (ART) resolves much of the immune dysfunction caused by HIV replication. However, reconstitution of the immune system during ART may, paradoxically, cause immunological disease that presents clinically as an immune reconstitution disorder. These disorders include autoimmune disease, mainly Graves' disease, and immune-mediated inflammatory disease, such as sarcoidosis. However, by far the most common type of immune reconstitution disorder results from restoring immune responses against oppor...

Understanding mechanisms of HIV-1 entry into cells

Human immunodeficiency virus type 1 (HIV-1) attaches to cells by the stepwise interaction of its envelope glycoproteins (Env), which exist as trimers that stud the exterior of the virus particle, with cellular CD4 and a coreceptor, principally either of the chemokine receptors CCR5 or CXCR4. Virus entry into cells then proceeds via exposure of a viral fusion peptide, and fusion between the viral and cellular membranes. Adaptability in Env conformation is a hallmark of HIV-1, which permits the virus to escape the humoral immune response. HIV-1 m...

Inflammation and innate immune activation in chronic HIV infection

Presently, there is no effective therapeutic HIV vaccine or a protective vaccine against de novo infection, and antiretroviral therapy is the only effective treatment for the many people currently infected with HIV. Current antiretroviral regimens, while effective at controlling HIV viremia, do not reduce inflammation and innate immune activation increased in chronically infected HIV+ individuals, who suffer increased prevalence of non-AIDS co-morbidities with an inflammatory aetiology. An understanding of the causes, and development of ...

Promoter targeted small RNAs: stabilising viral reservoirs

The viral reservoir, a major barrier to curative therapy for HIV-1 infection, consists of viral DNA sequestered in long-lived resting CD4+ T cells and macrophages in diverse anatomical sites. Some of these sites are recognised parts of the immune system, such as lymph nodes. Others, such as the brain are not 1. Current anti retroviral therapy (ART) does not substantially impact upon this reservoir. Early intervention with ART limits the reservoir but does not result in its elimination25.

HIV-specific ADCC: preventive and therapeutic vaccine potential

HIV vaccines based on neutralising antibody and CD8 cytotoxic T-cell immunity have failed to induce protection in phase III clinical trials, while live attenuated HIV vaccines (although effective in simian models) are considered too dangerous to use in humans due to reversion to virulence. New strategies and lateral thinking are required to develop a safe and effective vaccine against HIV. Antibody dependent cellular cytotoxicity (ADCC) represents one such modality that provides potential advantages over previous modalities and may also have a ...

Imaging of HIV entry and egress

During the early stages of HIV research, imaging of HIV was confined to the ultrastructural level1. These early images gave us glimpses of the viral life cycle from the early stages of entry, with HIV detection at the plasma membrane and within endocytic/vesicular compartments through to different sites of viral assembly/budding in CD4 T cells and macrophages15. Whilst these previo...

Science meets Parliament in Canberra: 2014

The ASM sponsored Kathryn Holt and Mike Manefield to participate in the Science Meets Parliament event in Canberra organised by Science and Technology Australia (STA) on the 16th and 17th of March 2014. Formed in 1985 in response to ‘wimpish’ lobbying efforts from the scientific community, STA represents 68,000 scientists and technologists and promotes their views on a wide range of policy issues to government, industry and the community.

Letter to the Editor

Joan Forrest Gardner DPhil (Oxon), AO: 16-6-1918 – 19-11-2013

Dr Joan Forrest Gardner was born in Melbourne on 16 June 1918, the only daughter of Dr John (Jack) Forrest Gardner and Dr Hilda Josephine Gardner. Her mother was an older sister of Sir Howard Florey, the famed developer of penicillin. Joan’s early life was beset by tragedy as her father died from tetanus after a car accident when she was 10 years of age and her only brother died six years later from a mastoid infection. Her mother then joined the staff of the Melbourne Hospital (now Royal Melbourne Hospital) where she became bacteriol...

Volume 35 Number 2

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