AIDS: the elusive vaccine

Over 30 million people around the world are living with HIV/AIDS, the vast majority of them in developing countries. In this issue Lumen profiles the global work of University of Adelaide alumni who are key international players in the fight against this insidious disease.

Since it was first recognised in December 1981, AIDS is estimated to have killed more than 25 million people, making it one of the most destructive pandemics in recorded history.

Current World Health Organization statistics show that about 0.6% of the global population is infected with HIV and the disease is spreading rapidly in Africa, where authorities predict it will leave at least 18 million orphans in the next few years.

Educating people about the dangers of unprotected sex and contaminated needles has had minimal effect in developing countries. The search, then, for a drug to reduce both the mortality and morbidity of HIV infection has never been more crucial.

Immunologist Dr Melissa Robbiani is playing a key role in this search as Director of Biomedical HIV Research at the Population Council, based in New York.

Dr Robbiani has an impressive history of contributions to the field. Her pioneering research has helped define the role of dendritic (immune) cells in HIV infection, leading to international acceptance of the theory behind how HIV is transmitted sexually.

In 1992, the University of Adelaide graduate left Australian shores armed with a PhD in Science and a passion to better understand the role of the cellular immune system in infectious diseases.

She headed straight to the Rockefeller University in New York to do her postdoctoral training with Dr Ralph Steinman, a world expert in immunology who first discovered the dendritic cell in 1973.

Under his mentorship, Dr Robbiani achieved a major breakthrough in HIV research, demonstrating that dendritic cells and a specific type of infection-fighting cell, known as memory T cells, provided a perfect environment for the spread of the HIV virus when isolated from skin.

Infection with HIV occurs by the transfer of blood, semen, vaginal fluid or breast milk. It is typically transmitted in four different ways: via sexual intercourse, contaminated needles, breast milk, and transmission from an infected mother to her baby at birth.

Dr Robbiani's research has centred on the pathway of the HIV virus during sexual transmission.

"HIV must breach the skin at the body surfaces to interact with and infect the white blood cells within and underneath the skin," Dr Robbiani said. "Once HIV breaches this barrier, it interacts with and can infect dendritic cells, macrophages or T cells. Dendritic cells are especially effective in capturing HIV and extremely efficient in transmitting the virus to T cells which amplify the spread of infection."

Direct exposure via injecting drug use is believed to be more potent than sexual exposure, but both forms of transmission occur.

Dr Robbiani said that despite the statistics, there is room for optimism.

"Our research focuses on understanding the basic biology of HIV transmission and the role of dendritic cells in this biology. We are making significant advances in this area, although there is still an enormous amount to learn about how to prevent infection through micro-biocides and vaccines."

A micro-biocide gel, Carraguard, has been trialled with some success, and will serve as the basis for new formulations.

"While there is still much to do, we are moving in the right direction," Dr Robbiani said.

On the other side of the Atlantic, Dr Graeme Moyle is a leading member of a multidisciplinary team at the Chelsea and Westminster Hospital, London, managing the day-to-day clinical care of HIV-positive individuals.

The hospital is northern Europe's largest HIV treatment centre and Dr Moyle's role encompasses clinical research.

"As Director of HIV Research Strategy I lead phase 2-4 research programs into all aspects of HIV infection. I take a special interest in developing new antiretroviral drugs and in managing disturbances of metabolism and morphology," he said.

The Mildura-born doctor was educated at Prince Alfred College and the University of Adelaide before heading to the UK, where he has spent the past two decades working in HIV care.

After graduating in 1986 with a Bachelor of Medicine, Bachelor of Surgery (MBBS), he completed his doctorate in 1996, with a thesis on the treatment of HIV infection with didanosine and foscarnet.

Dr Moyle's interest in infectious diseases was stimulated by a 5th-year elective at CMC Hospital in Vellore, India.

"A colleague at university was one of the first people in Adelaide to die of AIDS and I had several friends - both straight and gay - who were infected in the early 1980s," he said.

His clinical research is focused on antiretroviral drugs (substances that stop or suppress HIV) and also involves collaborating with the international AIDS vaccine initiative (IAVI). Dr Moyle is a UK investigator for a vaccine study run by biotechnology company Bionor and is also working with pharmaceutical company GlaxoSmithKline on their HIV vaccine.

"We have made fantastic progress in drug development in recent years but the number of new infections across the world is unacceptable and the pandemic is likely to get worse," Dr Moyle said.

"The growth in new infections is most evident in places with little access to care and little political will to address the problem."

Dr Nicholas Vandegraaff obtained his PhD in Virology as a Dawes Scholar from the University of Adelaide in 2002 under the supervision of Dr Li Peng and Professor Christopher Burrell.

After a four-year postdoctoral position at Harvard Medical School, Dr Vandegraaff took up his current job as Principal Scientist in Virology at the Melbourne-based pharmaceutical company, Avexa Ltd.

He leads Avexa's program aimed at identifying novel, small molecule inhibitors of HIV.

"Incredible progress has been made over the past 10-15 years in terms of our understanding of the HIV life cycle," Dr Vandegraaff said. "Fifteen years ago the life expectancy of someone diagnosed with AIDS was 1-2 years. HIV patients in industrialised nations can now expect something approaching a `normal' life expectancy thanks to antiretroviral therapy."

However, Dr Vandegraaff concedes that significant challenges lie ahead. Chief amongst these is the development of a vaccine.

"Current antiretroviral therapies are costly and therefore not readily available to developing nations who make up about 95% of the HIV/AIDS statistics. A successful vaccine will go a long way towards addressing the appalling HIV infection and treatment rates in Third World countries."

A second major challenge is to improve the quality of life for patients by developing treatments with fewer side effects, more activity and lower pill burdens.

"Such treatments are likely to reduce the number of drug-resistant viruses that are emerging within HIV-positive individuals."

Dr Vandegraaff said that while current antiretroviral therapies largely kept the disease under control, to date no-one has been cured of HIV infection.

"With HIV it is a constant race to stay one step ahead of the virus, which evolves at an extremely rapid rate," he said.

Dr Robert Ali is head of the South Australian-based World Health Organization Collaboration Centre in the Treatment of Drug and Alcohol.

The University of Adelaide medical graduate has been working in the field for the past 20 years. His current role focuses on evidence-based treatment for dependent drug users in the Asia Pacific region, including HIV-positive individuals.

Progress has been patchy, due mainly to governments in Asia pursuing a hardline prevention approach, which has not proved successful.

"These governments have tended to view drug use as a moral weakness, using harsh measures such as imprisonment to discourage continued drug use. But experience has shown us that this does not work. Drug addiction isn't a moral weakness; it's actually a medical condition," Dr Ali said.

Asian authorities are slowly coming to terms with this fact and starting to embrace a range of treatments sanctioned by the World Health Organization.

"China's response to the HIV pandemic was initially tepid but now they are dramatically increasing evidence-based treatments and as a consequence other countries in the region are following suit."

Vietnam is a case in point. It is following the example being set by China -- seen as an older brother -- and recently launched a national methadone treatment program.

In a bid to tackle the HIV epidemic, the Vietnamese Government has also turned to the University of Adelaide's Discipline of Pharmacology for help.

Epidemiologist Dr Ha Viet Dong, a Family Health International (FHI) program officer based in Ho Chi Minh City, completed a three-month placement at the University earlier this year to learn new skills in monitoring and evaluating methadone treatment programs.

Dr Ali said a collective will was needed among countries most affected by the HIV/AIDS pandemic to seriously address the problem.

"This is a human tragedy. The cost of doing nothing is an escalation of drug use and HIV spread. If we don't do something about the drug epidemic within Asia in the next two years the world will have a crisis on its hands."

STORY CANDY GIBSON