The only way to treat HIV (human immunodeficiency virus), as of now, is with medications that suppress the virus – meaning the virus is still in the body, just dormant. Therefore, the medication needs to be taken by the person for the rest of their life to keep the virus in suppression. This poses a particular challenge in developing countries where people don’t have enough money.
There were approximately 36.9 million people worldwide living with HIV/AIDS in 2017 and only 59% of these are receiving ARV, according to the World Health Organization. Drug-resistant HIV is a growing concern. Almost one million people die annually from HIV-related causes. That’s why scientists are doing everything they can to find a cure or a treatment that suppresses the virus for good, without requiring constant doses of drugs forever.
The study’s lead author, Professor Ravindra Gupta from the University of Cambridge, who led the study while at UCL, said:
“Finding a way to eliminate the virus entirely is an urgent global priority, but is particularly difficult because the virus integrates into the white blood cells of its host.”
CCR5
CCR5 is the most commonly used receptor by HIV-1 – the most common and most harmful type of HIV. People who have two mutated copies of the CCR5 allele are resistant to the HIV-1 virus strain that uses this receptor, as the virus cannot enter host cells. Chemotherapy can be effective against HIV as it kills cells that are dividing. Replacing immune cells with those that don’t have the CCR5 receptor appears to be key in preventing HIV from rebounding after the treatment.
The London Patient
According to a study published recently in Nature, a second person has experienced sustained remission from HIV-1 after ceasing treatment. The case report was carried out by researchers at UCL and Imperial College London, together with teams at the University of Cambridge and the University of Oxford. The first case – known as the ‘Berlin Patient` – was 10 years ago.
The subject of the new study, known as the `London Patient,` had his antiretroviral therapy (ARV) discontinued. Then, 18 months later, he was still in remission even though he hadn’t been taking the medication. This does not mean he has been cured! It is too early to dictate that the authors say. They will continue to monitor his condition to know what is happening for certain.
Professor Eduardo Olavarria, from Imperial College Healthcare NHS Trust and Imperial College London, said:
“While it is too early to say with certainty that our patient is now cured of HIV, and doctors will continue to monitor his condition, the apparent success of haematopoietic stem cell transplantation offers hope in the search for a long-awaited cure for HIV/AIDS.”
The Report
The patient was a man living in the UK who had been diagnosed with a HIV infection in 2003 and has been on antiretroviral therapy since 2012. By the end of 2012, he was diagnosed with advanced Hodgkin’s Lymphoma. Then, in 2016 he underwent chemotherapy and a received a haematopoietic (bone marrow) stem cell transplant from a donor with two copies of the genetic mutation (or ‘allele’) that prevents expression of CCR5.
16 months after the transplant, the patient was taken off his ARV treatment to test if the patient was truly in HIV-1 remission. 18 months after having been taken off of it, his levels of HIV-1 RNA and DNA are still so low as to be undetectable.
Dr Hoi Ping Mok, and Dr Fanny Salasc from the Department of Medicine at the University of Cambridge tests for viruses that are ‘latent’ and may not be found by conventional lab assays. His lab has developed a highly sensitive assay for latent viruses and the researchers from this ‘London Patient’ case are part of Professor Andrew Lever’s lab.
Professor Lever explained:
“This is the most reliable assay there is to demonstrate that there really are no hidden reservoirs of HIV that might be temporarily ‘sleeping’ and might reactivate at a later date. Our Cambridge lab is unique in the UK in being able to carry out this assay.”
The transplant itself was relatively uncomplicated. However, there were some side effects – including mild graft-versus-host disease, which is when the donor immune cells attack the recipient’s immune cells.
The Berlin Patient
The first person ever to be in sustained remission without ARV was the `Berlin Patient` – later identified as an American man named Timothy Brown – back in 2007. He underwent a similar, albeit more aggressive, treatment. He also received bone marrow stem cells from a donor with the same kind of genetic mutation, but to help treat leukemia instead, and they also treated him with total body irradiation, a risky procedure that can help the bone marrow transplant take hold.
Brown, however, suffered from multiple complications that had the potential to turn deadly. Which is why scientists had been unable to replicate the success of the treatment in the years since. They were not sure if his remission was a fluke, or actually caused by the treatment procedure, and it was too dangerous to test it. But now that it has happened again, it proves that Brown was not a fluke. The best part is, this second case was even successful with less aggressive treatment.
Professor Gupta said:
“By achieving remission in a second patient using a similar approach, we have shown that the Berlin Patient was not an anomaly, and that it really was the treatment approaches that eliminated HIV in these two people.”
Similarities And Differences
- Both patients were treated with stem cell transplants from donors carrying a genetic mutation that prevents the expression of the HIV receptor CCR5.
- Both patients experienced mild graft-versus-host disease, which may also have played a role in the loss of HIV-infected cells. It’s believed that the transplanted stem cells might help to eliminate host cells that are still infected with HIV, preventing the virus from returning.
- Notable differences were that the Berlin Patient was given two transplants and underwent total body irradiation, while the UK patient received just one transplant and less intensive chemotherapy.
In Conclusion
As promising as it is to have confirmation that a functional HIV cure is possible, the researchers do caution that the approach is not appropriate as a standard HIV treatment due to the toxicity of chemotherapy. The method overall is too complicated and risky but it offers hope for new treatment strategies that might eliminate HIV altogether.
Professor Anthony Kelleher, Director of the Kirby Institute at UNSW Sydney, said:
“The cost benefit of the prognosis following a bone marrow transplant versus that on HIV antiretroviral therapy needs serious consideration. Secondly, naturally resistant and compatible bone marrow donors are rare because of the need for donor recipient matching. Further, this type of procedure is not widely available in many countries. Finally, there is significant morbidity and mortality associated with this type of transplantation, even when conducted in the best centers, and under the best circumstances.”
Although, having shown that blocking the CCR5 gene works to fight HIV, the researchers are hopeful that gene therapy could be a less invasive treatment in the future. “We need to understand if we could knock out this receptor in people with HIV, which may be possible with gene therapy,” said Professor Gupta.
