HIV EXPLAINED

HIV remains to be a major global public health issue. According to the World Health Organization, HIV has claimed the lives of roughly 35 million people so far, and in 2020 it was estimated that 38 million people are currently living with the disease.

Our infectious diseases expert in this area is Professor Johnson Mak, Research Leader at the Institute for Glycomics. In this blog article, Professor Mak delves into the details of this very clever, yet deadly, virus and why prevention is so extremely important.

Let’s start with the basics…

What is HIV?

HIV stands for ‘Human Immunodeficiency Virus’.  As the name suggests, the human immunodeficiency virus attacks the immune system, weakening a person’s natural defence mechanism against infection.

As the virus destroys and impairs the function of immune cells, the infected patient will gradually become immunodeficient, which increases their susceptibility to a wide range of diseases that people with healthy immune systems can usually fight off.

If left untreated, HIV infection can lead to the disease acquired immunodeficiency syndrome (AIDS). AIDS is the most severe phase of HIV infection, where the immune system is so badly damaged that it is extremely susceptible to opportunistic infections. Without treatment, people with AIDS typically only survive about three to ten years.

When was HIV first discovered?

AIDS was first identified in the early 1980s, but the causative agent HIV was only identified in 1983 by the laboratory of Luc Montagnier at the Pasteur Institute in Paris through efforts led by Françoise Barré-Sinoussi. This work of Barré-Sinoussi and Montagnier on the discovery of HIV was recognised by the Nobel Committee in 2008 and they were awarded with the Nobel Prize in Physiology or Medicine that year.

How is HIV contracted by humans and how is it spread?

HIV is a blood borne virus that is transmitted via direct contact with body fluids, such as blood, semen or vaginal fluids, that contain high levels of the virus.

What makes this disease so serious?

1. First, HIV infects human immune cells known as CD4+ T lymphocytes that are critical in eliciting a strong immune response to fight off infection. By weakening our immune system, HIV-infected individuals are prone to opportunistic infections that normally would pose no risk to healthy individuals. In essence, HIV weakens our defence (immune) system so we’re unable to fight off infections.
2. Second, HIV is a lentivirus, which means that there is a delay in the onset of symptoms after infection; it has the ability to insert its genetic materials into the host cells and disguises itself as part of normal host cell genetic materials. This process is known as integration. Once integration occurs, infected cells will have the capacity to produce the next generation of viruses, until these infected cells die. HIV-infected cells are also able to pass HIV genetic materials to their daughter cells.
3. Third, the enzyme that HIV relies on to replicate its genetic materials is known as reverse transcriptase, which has one of the higher mutation rates among similar types of known enzymes. The ability for HIV to mutate rapidly means that HIV is always one step ahead of our immune system, making it even more difficult to develop an effective immune response against infection.
4. Fourth, the virus surface protein is decorated with a large amount of sugar molecules, and the HIV surface protein is one of the most sugar-decorated proteins known to humans. These sugar molecules act as a shield – a ‘glycan shield’ – which protects some of the weakest spots of the viral particles, thereby preventing the human immune system from fighting the virus.

What is the global impact of HIV?

Currently, there are roughly 38 million people across the world who are living with HIV. Roughly, 35 million have died from HIV. In 2020, there were 1.5 million new infections (that’s roughly one new infection every 20 seconds).

What’s probably most alarming about these statistics is that there are many people living with HIV and spreading the disease without realising they are infected. In fact, it’s estimated that 7.1 million people around the world are HIV positive but do not know that they are.

Current treatment options for HIV

HIV can be treated using a combination of three or more anti-retroviral (ARV) drugs. ARV drugs cannot cure HIV infection, but greatly suppresses viral replication within the human body, allowing the immune system to recover and strengthen enough to regain the ability to fight off infections.

Under the appropriate guidance and monitoring of health care physicians, HIV-infected individuals can live a fairly normal life by continuously receiving this combination anti-retroviral therapy. With continuous advances in anti-retroviral therapies, HIV infection can be managed to bring the virus to undetectable levels. It has been shown that the risk of being infected by an HIV positive individual with an undetectable viral load is extremely low.

Unfortunately, the treatment of HIV is lifelong as there is currently no way to get rid of the last trace of virus in the body. Pausing the combination anti-retroviral therapy will lead to viral rebound via reactivation of HIV latently infected cells.

In an ideal world, HIV-infected individuals should be receiving treatment to control the spread of HIV and lower the risk of community transmission. However, in reality, millions of people around the world do not know that they are HIV positive.  Exasperating the issue further, in some areas of the world, e.g., countries without universal healthcare or low- and middle-income countries, patients do not have guaranteed access to, or cannot afford, treatment.

In 2019, about 68% of HIV-infected individuals were receiving drug treatment, meaning 12 million people are currently not being treated.

HIV and pregnancy

HIV-infected women have the ability to pass HIV onto their children during pregnancy, labour, delivery or breastfeeding. According to the World Health Organization, in the absence of any interventions during these stages, rates of HIV transmission from mother to child can be anywhere between 15% and 45%.

However, transmission of HIV from mother to child generally occurs with patients who are not receiving treatment. The risk of transmission can be almost eliminated if both mother and child are provided with ARV drugs as early as possible in pregnancy and during breastfeeding. There are many examples of HIV-infected mothers or couples who have had biological offspring that are HIV negative.

Can you explain in simple terms your research approach to this virus and what you hope to achieve?

There are two major parts to the HIV research currently being carried out by my research group at the Institute for Glycomics.

In the first part of our HIV work, we interrogate the process of virus formation and how these virus formation processes will make progeny viruses capable of targeting the next cell (transmission). Within this line of work, we are particularly interested in the contribution of sugars in the formation of infectious virus particles.  

We hope to take advantage of the virus assembly and entry mechanism we identify in order to develop an effective and inexpensive mitigation strategy to repress HIV transmission. A major goal of this work is to assist some of the most vulnerable populations in our society. Unfortunately, HIV is both a gender inequality and a wealth inequality problem. Low- to middle- income countries account for the majority of HIV infection, and more than half of the new infections are women. We hope that some of our research can ultimately provide positive solutions for these affected populations. In this approach, mitigation is the primary goal.

Next steps: we are about to commence analyses to visualise how the sugar components of the HIV surface protein contribute to the infection process. We will use a technology known as electron microscopy that allows us to see the fine details – that is, one billionth of a meter in size – to delineate the interplay between virus and host cell, including rapidly cooling our sample to a very low temperature (-196^oC) under high pressure to preserve the morphology (structures) of our virus and cells.

In the second part of our HIV work, we have designed a new type of vaccination strategy that we hope will ultimately help the human immune system to penetrate through the ‘glycan shield’ to elicit a robust immune response that can block HIV infection.

Next steps: we are developing a vaccine strategy that can offer protective benefits to affected populations. In this approach, protection is the primary goal. Pre-clinical evaluations are underway.

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