“London patient”: second cure for HIV?

Attempts to repeat the experience with the long-term remission of HIV infection 12 years ago seemed to be successful, a so-called “London patient” became the second person who recovered from HIV infection, whose name has not yet been disclosed.

According to researchers, this is another crucial milestone in the fight against the HIV / AIDS epidemic - a means by which, perhaps, the virus will be defeated, exists.

Reportedly, an article revealing the details of the study will be published in the journal Nature on Tuesday.

At the conference, the case of the “London patient” was reservedly characterized by specialists as a long-term remission. The means by which this was achieved is bone marrow transplantation to an HIV-positive patient from a donor with a mutation of the CCR5 delta 32 gene, most experts call the cure with a reservation, because it is still not clear why the technique worked on Berlin. and "London" patients and did not give an answer in other cases.

Bone marrow transplantation is unlikely to become a common treatment option in the foreseeable future, scientists say. Today, effective drugs for suppressing HIV are almost universally prevalent, while transplantation is a risky operation, with serious side effects that can last for years.

However, the process of changes in the body of immune cells to modified ones that can resist HIV may well become a successful direction of practical treatment.

“It will inspire people and make them understand that treatment is not an impossible dream. A cure is possible, ”commented on the discovery of Dr. Annemarie Vensing from the University of Utrecht Medical Center in the Netherlands.

Dr. Vensing is one of the specialists from IciStem, a consortium of European scientists involved in stem cell transplantation for the treatment of HIV. The consortium is supported by AMFAR, an American HIV / AIDS research organization.

As the expert explained, a person with a mutation of the CCR5 gene, a receptor located on the surface of a number of immune cells, which allows HIV, using a bunch with it, to penetrate the cell wall was chosen as a bone marrow donor for an HIV-positive patient with cancer. The CCR5 delta32 mutation has not been found to prevent most HIV strains from using the receptor to enter cells, thus making a person not susceptible to HIV.

The “Berlin patient” Timothy Ray Brown, who for the first time during his observation, achieved sustained long-term remission of HIV, after undergoing a similar procedure, took extremely severe immunosuppressants and had serious complications as a result of the transplant. According to the people who worked with him, at some point his condition was so severe that he had to be put into an artificial coma.

“He was really exhausted by this procedure,” said Dr. Stephen Dix, an expert on HIV / AIDS at the University of California who had treated Brown, “so we have since wondered if Timothy’s cure explains that he had to undergo system. "

The case of a patient from London answered this question: in order for the procedure to work, no full repetition of Brown’s experience is required.

In the newly discovered case of remission, the patient had Hodgkin's lymphoma, and he also received a bone marrow transplant from a donor with a mutation CCR5 delta 32 in May 2016. The patient, like Brown, received immunosuppressants, but his treatment was much less intensive, because it was built in accordance with modern standards of therapy for patients undergoing transplantation.

The London Patient achieved sustained remission of HIV and stopped taking ART, in September 2017. This made him the first person since Brown recovered, in whom the virus was not detected in the blood for more than a year after stopping ART.

“I think this will change the rules of the game a bit,” said Dr. Ravindra Gupta, a virologist at University College London, who presented the results at a conference in Seattle. “After the Berlin patient, everyone believed that it was almost necessary to die to cure HIV but now it turned out that this is not the case. ”

Despite the fact that the “London patient” did not experience those side effects after transplantation that Brown had experienced, the procedure in his case worked much the same: the bone marrow tissues destroyed the cancer without serious side effects. In addition, new HIV-resistant immune cells are likely to completely replace those vulnerable to the virus.

The vast majority of people with the CCR5 delta32 gene mutation are of North European origin. The IciStem consortium that deals with this issue has a database of about 22,000 such donors.

To date, its scientists have been tracking 38 people with HIV infection who received bone marrow transplantation, six of them from donors without mutation. In addition to the “London patient,” experts also distinguish among them a person called “Düsseldorf 

patient, who has achieved remission and has not taken ART for 4 months. Details of this case will also be presented in Seattle this week.

According to experts working with the "London patient," his body was repeatedly tested for signs of a virus. However, even the most sensitive test found no signs of HIV. The study of blood tests recorded the presence of antibodies to the virus, but their levels gradually decreased, resembling the trajectories previously observed in Brown.

Despite this, Gupta said on Monday, none of the above guarantees that the “London patient” is permanently cured. However, at the same time, he added, the similarity with the recovery of Mr. Brown gives grounds for optimism.

Most experts who are familiar with the details of the discovery agree that the new case confirms the effectiveness of the HIV treatment mechanism, but some still do not fully believe that it will prove to be really significant for the final victory over the virus.

“I’m not sure that this tells us something,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases of the United States. so what now? Where are we going with this now? ”

According to Dr. Dix and a number of other specialists, one of the possibilities is the development of gene therapy approaches to destroy CCR5 on immune cells or their precursors. Modified cells that are resistant to HIV strains, they are confident, should eventually cleanse the body of the virus.

Currently, several companies are conducting gene therapy at once, but so far they have not achieved significant success. Gene modification should be targeted, having as a goal a certain number of cells in a particular tissue segment - for example, only in the bone marrow - and only tune the genes that are involved in managing the production of CCR5.

“There are a number of levels of accuracy that need to be achieved,” said Dr. Mike McQueen, senior global health advisor to the Bill and Melinda Gates Foundation.

According to him, several groups of scientists are already working on this. In the end, the specialist is confident that they will be able to develop an agent delivery system that, when introduced into the body, will search for all CCR5 receptors and remove them.

Dr. Timothy J. Heinrich from the University of California disagrees with this assessment. “It only works if someone has a virus that uses the CCR5 receptor to enter — and this is probably about 50% of people living with HIV, if not less. "

According to the expert, the patient will still be vulnerable to HIV with an X4 tropism, which another CXCR4 protein uses to enter the cells.