Two patients have astonishingly cured themselves of HIV without any therapy. Kevin Boyle discusses these novel findings and their potential implications in the development of a vaccine against the HIV virus.
A recent report in the Annals of Internal Medicine has shown that a female patient previously infected with HIV was able to remove the infection from her body without the use of medication. The report discusses the findings of Dr Xu Yu’s research group at the Ragon Institute in Boston, Massachusetts who screened over a billion of the HIV patient’s cells and found no trace of the virus. This is a very exciting result as it potentially paves the way for the development of a potent HIV vaccine.
The woman, known as the Esperanza patient after her home town in Argentina, is the second patient studied by Dr Yu’s group to spontaneously recover from HIV, through what has been termed a “natural cure”. The research on the first patient, known as the San Francisco patient, was published by Yu’s group in Nature in 2020. Prior to these cases, only two people had ever been cured of HIV after undergoing risky and unpredictable bone marrow transplants. Many other attempts at this surgery have been made but failed.
While the above examples are the first of their kind, it has been known for over 20 years that a very small number of HIV sufferers (less than 0.5% of the 38 million diagnosed), labelled as “elite controllers”, can control the virus naturally. This was first shown in 1998, when Professor Joel Blankson of the John Hopkins Institute of Medicine, Baltimore ran a routine test on an HIV positive patient but unexpectedly found no trace of the virus. Further examples have been found over the years that have left researchers puzzled. Research has been focussed on trying to discover how elite controllers are able to achieve natural recovery. Scientists hope that their immune response could be mimicked in the pursuit of new therapies that could surpass the standard HIV treatment – a cocktail of drugs called antiretroviral therapy (ART) or highly active antiretroviral therapy (HAART).
T-cells are a vital component of a healthy immune system and are responsible for killing viral cells. The HIV virus has proven difficult to eradicate as it targets and destroys T-cells, thus weakening the immune system and allowing the virus to spread throughout the body. ART counters this mechanism by maintaining high levels of T-cells. The combination of several drugs used in ART stops the virus replicating by interfering with the function of key replication enzymes, namely protease and reverse transcriptase, which stops the virus replicating in host cells. Although ART is not a cure for HIV, it has been highly successful as it enables the patient’s body to control the virus, ultimately allowing patients to live normal lives. However, new therapies are desirable as the current drugs against HIV are expensive, toxic and often incompatible with many other drugs a patient might be taking. The toxicity is caused by an imbalance of enzymes which can lead to liver damage. Furthermore, the therapy requires that the patients take the drug routinely every day for the rest of their lives in order to maintain low viral loads. If doses are missed, the virus becomes resistant to the drugs, and if therapy is stopped, the virus quickly spreads.
Despite the success of ART, it is clear that new therapies without the above limitations would be advantageous for patients. It is hoped that such therapies could be found through a better understanding of how the immune systems of elite controllers work. However, due to the limited sample size of elite controllers, scientists haven’t been able to determine the exact mechanism of natural recovery but several hypotheses exist. For example, it has been known for some time that 65% of elite controllers contain an unusual variant of a gene (the human leukocyte antigen B gene), which is responsible for controlling the immune response. This variant produces powerful “killer” T-cells that recognise multiple parts of the HIV virus, increasing the probability that the T-cells will recognise and kill HIV infected cells. More recently, Dr Yu’s group has shown that the virus in elite controllers exists in an area of the human chromosome that is largely inactive, meaning that the virus can’t multiply or harm healthy cells. Another school of thought comes from Professor Blankson who suggests that natural killer cells (another important immune system cell) are primed to attack infected cells faster than normal – they act within the first day of infection compared to T-cells that take up to two weeks to produce an immune response. Finally, “viral reservoirs” are a known characteristic of HIV, where the virus accumulates and “disguises” itself in cells making it undetectable to drugs. Research has shown that elite controllers have the unique ability to remove most, or even all, of the HIV reservoir.
Over the years, it has proven impossible to produce an HIV vaccine for several reasons: the virus mutates a lot and quickly (within 24 hours), it targets T-cells and evades vaccines through hiding in the reservoirs. However, the discovery of the Esperanza and San Francisco patients has made scientists optimistic that a cure for HIV might be on the horizon. Dr Yu believes that by mimicking the biological mechanisms of elite controllers a vaccine can be developed that trains the body to function without needing ART. Further optimism comes from Dr Beatriz Mothe at the IrsiCaixa Aids Research Institute in Catalonia, Spain, who thinks that by understanding how the T-cells in elite controllers target specific locations on the virus, the so-far elusive vaccine will be one step closer to becoming a reality.
Written by Kevin Boyle and edited by Natasha Kisseroudis
Kevin studied Chemistry as an undergrad and later pursued a PhD in Organic Chemistry at the University of Edinburgh before later undertaking a Masters in Chemical Biology at Imperial College London. He now works as a full-time Chemistry tutor.