'Elite controllers' may provide clues for HIV cure

"Scientists have uncovered the genetic mechanism which appeared to have led two HIV-infected men to experience a 'spontaneous cure’," the Mail Online reports.

The men are what is known as "elite controllers": people thought to have high levels of immunity against the virus, as they do not develop any symptoms of HIV, despite going untreated.

Both men had no trace of HIV in blood tests that are normally used to detect the virus, but did have the virus in their DNA. This study found that there had been a mutation in the virus, meaning it was unable to replicate. This mutation may have been caused by the increase of an enzyme called APOBEC, which is usually inhibited by HIV infection.

Current treatment of HIV involves taking anti-viral medication to keep the spread of the virus (viral load) minimised, so it doesn’t cause any symptoms. This treatment regime has actually been remarkably successful – one of the great achievements of modern medicine. However, the major drawback is that the person has to take drugs every day. This research may offer the possibility of modifying the HIV virus, making it harmless – thus achieving, to all extents and purposes, a complete cure.

The researchers now wish to determine if this same mutation is present in other people who appear to have immunity to HIV infection.

Where did the story come from?

The study was carried out by researchers from Aix-Marseille University, hospitals in Marseille, the University of Paris Est, and the Vaccine Research Institute in Créteil. The study was reported to be funded internally and the authors declare no conflicts of interest.

The study was published in the peer-reviewed medical journal Clinical Microbiology and Infection.

The Mail Online’s reporting of the study was accurate and provided useful insights from the study authors.

What kind of research was this?

This was a case study of two people who were HIV positive, but with no symptoms. These people are known as “elite controllers” as they seem to have an innate immunity against infection.

It's difficult to estimate exactly how common elite controllers are as, by their very nature, they remain free of symptoms, so they often go undiagnosed. They usually only come to light if a sexual partner or fellow drug user contracts HIV, so they are offered testing. The current best guess is that less than 1 in a 100 people have this immunity.

The researchers aimed to study the immune response of these two elite controllers to HIV infection, to understand why they have been asymptomatic.

What did the research involve?

The researchers investigated the DNA of two men who had been diagnosed with HIV in 1985 and 2011, but who had no HIV-related disease and no HIV detection in their blood after undertaking routine tests.

They performed laboratory tests to investigate how the HIV had been incorporated into the host DNA without it replicating. They also looked at the individual’s immune response to the HIV.

What were the basic results?

Viruses isolated from both men were inactive, meaning they could not spread in the men’s bodies, causing illness. This was due to a change in the genetic code of the virus, which effectively stopped it from replicating. For the geneticists out there, this involved many transformations of tryptophan codons into stop codons.

This transformation causes problems for the virus, as it can’t make the proteins it needs correctly. A specific enzyme called APOBEC makes this change, and this enzyme is usually inhibited by HIV infection.

The researchers speculated that, in these individuals, APOBEC might have been stimulated when they were first infected.

How did the researchers interpret the results?

The researchers concluded that their, “findings, which warrant further confirmation, are a first step in understanding the resistance to retroviruses. They may allow us to figure out the endogenisation [internal development] of retroviruses and detect resistant patients, as well as to initiate strategies of imitations of these patients to cure or prevent AIDS”. In other words, they suggest a new strategy for HIV treatments that does not require full eradication of the virus; instead, it allows incorporation of the virus into the DNA, but inactivating it. This is a new way of thinking.

Conclusion

This interesting research has found a likely reason for the apparent immunity of two men to HIV infection. This was through a transformation of an amino acid in the genetic code of the virus that stops it from replicating. The researchers now wish to reproduce their findings by looking at samples from other people who appear to be resistant to HIV infection. The next step in the quest for a cure would be to determine how to replicate this genetic switch in amino acids in people without natural resistance.

The results of the study have no immediate treatment implications, but do increase understanding of the virus and the disease, so could aid development of future treatments.

While current anti-viral treatment is effective, it usually requires a person to take drugs for the rest of their life, which can sometimes cause unpleasant side effects.

Therefore, a drug that could achieve a complete cure by stopping the HIV virus replicating would have a significant positive impact for people living with HIV.