Human Immunodeficiency Virus (HIV) infection places an immense burden on global health. The virus causes Acquired Immune Deficiency Syndrome (AIDS) by depleting infection-fighting immune cells. There are medications that are effective in preventing people with HIV developing AIDS, but no cure. Our researchers are working to improve how HIV is treated, with the goal of curing this infection.

HIV research at WEHI

Our researchers aim to improve treatments for people infected with HIV. Their focuses are:

• Revealing why the immune system cannot clear HIV from the body.
• Developing new ways to enhance the immune response against HIV, as a potential cure.

Our researchers also investigate many significant illnesses that affect people with AIDS, including:

• Cryptococcosis
• Toxoplasmosis
• Tuberculosis
• Lymphoma
• Stomach cancer

What are HIV and AIDS?

HIV is a virus, meaning it can only reproduce within another organism’s cells. HIV reproduces in certain human immune cells, particularly a type of immune cell called CD4 T cells. These cells are critical for many immune responses that protect against infections.

When a person is infected with HIV, they may initially be healthy and not realise they are carrying the virus. Without treatment, people infected with HIV usually stay healthy for around 10 years. However, the infection gradually kills their CD4 T cells. This means their immune system cannot function properly.

Someone infected with HIV and not receiving treatment will eventually develop a condition called Acquired Immune Deficiency Syndrome (AIDS). In this condition, the loss of CD4 T cells means the person’s immune system cannot fight infections. People with AIDS are at risk of severe infections by viruses, bacteria and fungi. Often these are infections that a healthy immune system can prevent. A person with AIDS will ultimately die from an overwhelming infection.

More than 27,000 Australians are infected with HIV. Most of these people receive appropriate treatment. This prevents their disease progressing to AIDS. The Education and Resource Centre at the Alfred provides support and information for Victorians living with HIV.

Globally, around 37.9 million people are infected with HIV. The majority of people living with HIV are aged 15 to 49. AIDS-related illnesses cause 770,000 deaths annually, mostly in resource-poor communities. HIV infection is an enormous health, social and economic burden globally.

How is HIV spread?

HIV is a type of virus called a retrovirus. It consists of:

• An outer membrane, or envelope, made of lipids and proteins
• The virus’s genetic content, or genome. This is made of the DNA-like molecule, RNA.
• Internal proteins that help the virus infect cells.

HIV can be transmitted between people through contact with infected bodily fluids. The main sources of HIV infection globally are:

• HIV-infected blood: In Australia, blood donations are screened to ensure they do not contain HIV or other viruses. Syringe needles contaminated with HIV are another potential source of infection.
• Sexual contact: HIV is present in semen and vaginal fluids.
• From mother to child: during pregnancy or birth, or through infected breast milk. This can be reduced by medical interventions including appropriate medical treatment of pregnant women infected with HIV.

When an HIV viral particle enters the body it can infect immune cells called CD4 T cells.

The stages of HIV infection of CD4 T cells are:

• Entry into the cell: The virus binds to certain proteins on the outside of CD4 T cells. This allows the viral proteins and genome to enter the cell.
• Reverse transcription: A viral protein converts the viral genome, made of RNA, to DNA. The genome of human cells is made of DNA.
• Integration: The viral DNA joins into the cell’s DNA. This allows the virus to hide within the cell. It may lie dormant for several years.
• Production of new viruses: The HIV DNA within the cell directs the formation of new viral genomes and proteins. These assemble into new viral particles.
• Release from the cell: The new HIV particles leave the cell, and can infect other cells.

Not all CD4 T cells that are infected with HIV go on to produce new viruses. Often, the CD4 T cells will detect the viral DNA that is produced by reverse transcription. This can trigger the death of the infected cell as a protective response.

How is HIV treated?

There is currently no cure for HIV, and no preventive vaccine.

Understanding how HIV infects cells has led to anti-viral medications that block the different stages. These agents prevent HIV from spreading between cells within the body. This stops the loss of CD4 T cells, allowing the HIV-infected person to stay healthy.

People infected with HIV can receive lifelong anti-viral treatments that stop the loss of CD4 T cells. This prevents AIDS, and allows a near-normal life. Appropriate treatment can also reduce the chance that someone infected with HIV infects other people, particularly for mother to child transmission. Anti-viral treatments can also prevent HIV infections if given immediately after exposure.

When HIV replicates, its genome and proteins may slightly change (mutate). Occasionally these changes mean that the new HIV viral particles are resistant to the actions of an anti-viral medication. If this occurs, the resistant virus will spread unhindered in the body, and the treatment will be ineffective. The best strategies to treat HIV use several different anti-viral medications at once. This reduces the chance that resistance to one treatment can occur.

In poorer communities, the cost of long-term treatment for HIV can prevent people from accessing the best treatment. This increases the chance that they will develop AIDS and die. There is an urgent need for a cure or preventive vaccine for HIV.