It is four decades since the emergence of HIV/Aids sent shockwaves through societies across the globe.
In the 1980s and 1990s, an infection with the human immunodeficiency virus, whether from a blood transfusion, sexual activity, intravenous drug use or another cause, was often seen as a death sentence.
One particularly chilling Australian television advertisement from 1987 featured the Grim Reaper and the words, "Aids: prevention is the only cure we’ve got."
It is the search for a cure that featured among discussions at the recent Arab Health conference in Dubai, with some cautious optimism that one could be developed.
Prof Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity in Melbourne, told attendees that there was a "quite high" chance of finding a cure and hoped one could be delivered within the next two decades.
A cure would be welcome in the Mena region because, as Prof Lewin highlighted, it faces an "alarming" rise in cases, something that contrasts with the falls typically seen elsewhere.
Some other parts of the world are still severely affected by the illness. Africa accounts for most of the global total of more than 40 million deaths so far from Aids. This is out of more than 80 million people worldwide who have been infected with HIV.
Terrible though the death toll is, since the second half of the 1990s the situation has been much improved, especially in areas with well-funded healthcare systems. This is because infection can be managed effectively with antiretroviral treatment, which is typically taken daily.
These drugs help to prevent the virus from replicating, which reduces a patient’s viral load, the number of virus particles in the blood.
Antiretrovirals maintain high levels of CD4 cells, a type of white blood cell that stimulates the immune system, preventing the onset of Aids. If the CD4 cell count falls, the person becomes highly vulnerable to infection.
Patients who begin taking medication relatively soon after becoming infected often have a life expectancy similar to those without HIV.
What is more, antiretroviral drugs that need be injected every two months only are now being used in some countries, meaning that patients no longer have to take tablets daily.
Chronic low-level inflammation associated with HIV infection does, however, put people living with the virus at greater risk of, for example, heart, kidney and liver problems.
As a result, eliminating the infection remains a goal.
Given the myriad strategies being looked at, progress in preventing infection, or in treating or curing those who become infected – there are about 1.5 million new infections annually across the world – seems likely.
Already, in a small number of cases, the virus has been eliminated from patients’ bodies, something known as a sterilising cure.
The first and probably the most famous example concerns the Berlin Patient, real name Timothy Brown, who had leukaemia and so received a stem-cell transplant.
The donor had a mutation in a gene called CCR5, which makes the carrier almost completely resistant to HIV.
Great interest was sparked when, in 2008, it was revealed that this transplant had enabled Mr Brown’s body to rid itself of the virus, although he went on to die in 2020 after his leukaemia returned.
A number of others have been cured after transplants, but these are risky for those living with HIV. They typically have side effects, and they are not seen as a realistic cure for large numbers of patients.
Other methods to achieving a sterilising cure are being investigated. One is known as "shock and kill", a dramatic term that refers to using one drug to activate HIV lying dormant in cells before other drugs, such as normal antiretrovirals, destroy it. Several pharmaceutical and biotechnology companies are working on their own version of this.
Another strategy, often involving therapeutic vaccines, strengthens the immune system to help it attack HIV.
One approach has already reached clinical trials and been shown to be effective at enabling patients to live at length without the need for treatment.
Several other immunotherapy strategies, such as using broadly neutralising antibodies, which can prevent HIV from entering healthy cells, are at various stages of development and have in some instances shown promising results.
Often these offer the prospect of what is sometimes referred to as a functional cure, where the virus is still present, but it has been controlled without the need for ongoing treatment.
Another exciting avenue of research concerns preventive vaccines against HIV, in particular messenger RNA shots.
Developing an effective vaccine against HIV has been described by Prof Robin Shattock, of Imperial College London, as "one of the biggest biological challenges of a generation", but it is one that is moving closer to being achieved.
The Covid-19 pandemic led to the first large-scale use of mRNA vaccines in people. Now numerous companies and other organisations are working to test shots against HIV based on the same technology.
Early clinical trials have been successful, with injections being able to stimulate the hoped-for immune response in the vast majority of participants.
Even if a cure, more sophisticated treatments or vaccines are released, ensuring access is likely to be an issue.
Although the proportion of people who have access to antiretroviral treatment has significantly improved in recent years, about a quarter of the estimated 38.4 million people living with HIV are still not using the drugs.
So, although the number of deaths each year has dropped by more than half since its 2004 peak, 650,000 people still lost their lives from Aids-related illnesses in 2021, according to UN figures.
In the years to come, equitable distribution is likely to remain as much of a challenge as the science.
