There are 5 cases of people cured of AIDS in the world. Can the method of conquering AIDS be replicated?

AIDS, the full name of which is "Acquired Immune Deficiency Syndrome" (AIDS), is an infectious disease caused by the human immunodeficiency virus (HIV) that seriously threatens human health. After HIV infects the human body, it does not immediately cause AIDS. It takes a process for the virus to replicate in the human body and cause the disease, so they are divided into two groups: "HIV-infected people" and "AIDS patients."

In recent years, there have been more and more cases of AIDS being cured. Does this mean that humans have broken the curse of AIDS? Can the cure be replicated and used by more people?

A list of five AIDS patients who were declared "cured"

At present, there are a total of five AIDS patients in the world who have been declared "cured", namely the "Berlin Patient", the "London Patient", the "Düsseldorf Patient", the "New York Patient" and the "City of Hope Patient".

Berlin patient : received bone marrow stem cell transplant and died of cancer recurrence in 2020.

HIV mainly invades the human immune system, focusing on CD4+T lymphocytes. Similar to the new coronavirus, HIV also needs an auxiliary receptor to invade human cells - CCR5 (which can be understood as the key to open the door of the cell). If the human body does not have this "key", HIV will not be like a scumbag, draining this cell and looking for the next new love in a glamorous way.

Coincidentally, the world's first case of AIDS cure was related to CCR5.

His name is Timothy Ray Brown, who suffers from both leukemia and AIDS. In 2007, Brown received a bone marrow transplant in Berlin, Germany, and his HIV was eliminated. When treating leukemia, Brown first received radiation therapy to kill cancer cells and stem cells that produce cancer cells in the bone marrow, and then received a bone marrow transplant from a healthy donor to produce new blood cells.

The bone marrow donor carried the CCR5-Δ32 gene mutation, which resulted in the loss of CCR5. Scientists analyzed that it was probably because Brown also had this valuable gene mutation after receiving the bone marrow transplant that the newly born immune cells lacked the protein receptors that could bind to the virus. The virus lost the "key" to invade cells to proliferate itself, and was eventually completely eliminated by the human body.

On September 30, 2020, the International AIDS Society issued a statement that Brown had died of a recurrence of cancer at the age of 54.

London patient : received bone marrow stem cell transplant, confirmed by The Lancet in March 2020.

In 2019, a study was published in the famous academic journal Nature. An HIV-infected person known as the "London patient" entered sustained remission of HIV infection after receiving hematopoietic stem cell transplantation therapy for lymphoma. Even after stopping taking antiviral drugs, no signs of HIV recurrence were found in the following 18 months. Subsequently, the authors changed the evaluation of the "London patient" after CCR5-Δ32 hematopoietic stem cell transplantation published in Nature from "long-term remission" to "cure".

Düsseldorf patient : bone marrow stem cell transplantation was used, confirmed by Nature in February 2023.

On February 20, 2023, researchers from the University Hospital of Düsseldorf and other institutions in Germany published a paper in the top international medical journal Nature Medicine, reporting that a 53-year-old German male AIDS patient was diagnosed with acute myeloid leukemia in January 2011. He received a CCR5-Δ32 stem cell transplant from a female donor in February 2013. Nine years after the transplant and four years after stopping antiretroviral treatment, he showed sustained suppression of HIV-1. Since then, the research team has not detected the presence of HIV-1 in his body even with the most accurate detection methods, and most experts believe that this situation can be called "cured."

New York patient : Through umbilical cord blood stem cell transplantation, she is the only female AIDS patient who has been "cured" so far.

On February 15, 2022, a research team from UCLA and Johns Hopkins University reported a case of AIDS treatment: a female AIDS patient who received umbilical cord blood stem cell transplantation to treat acute myeloid leukemia had no detectable HIV virus for up to 14 months after stopping antiretroviral drug treatment.

On March 16, 2023, researchers from Weill Cornell Medical College and other institutions published a paper in the journal Cell, stating that the "New York patient" is the only female among the five AIDS patients who have been declared "cured" and is of mixed race.

City of Hope patient : The oldest person to be cured of AIDS through bone marrow stem cell transplantation.

The "City of Hope patient" is a 68-year-old male patient. He was diagnosed with HIV-1 in 1988 and later developed leukemia. After receiving a CCR5-Δ32 bone marrow stem cell transplant in 2019, he stopped taking antiretroviral drugs for more than 17 months, and doctors did not find any signs of HIV-1 replication. On July 27, 2022, the City of Hope National Cancer Center in the United States announced that he was "cured."

On February 15, 2024, researchers at City of Hope published a paper in the New England Journal of Medicine (NEJM) reporting on the treatment of the "City of Hope patient." The patient is believed to have been cured of leukemia, and it has been 5 years since the transplant treatment. The patient has no HIV-1 infection and stopped taking antiretroviral drugs for AIDS treatment 3 years ago.

Can the treatment model of HIV survivors be replicated on a large scale?

The five AIDS survivors mentioned above have many similarities. First, they were all suffering from AIDS and cancer; second, they all underwent hematopoietic stem cell transplantation; and third, those who are willing to donate bone marrow must carry the CCR5-Δ32 gene mutation, which means they are resistant to HIV.

So, what proportion do the above three conditions each account for in the healing process? Let's analyze them one by one:

① People with HIV are more likely to develop cancer

The reason why AIDS can kill people is because the HIV virus can cause an imbalance in human immune function.

Healthy people have a balanced immune system, so tumors and cancerous cells in the body can be detected and removed in a timely manner, keeping us healthy. But for HIV-infected people, due to their reduced immune function, cells are prone to mutation, especially cancer, which cannot be controlled by the immune system, so HIV-infected people are more likely to develop tumors than healthy people.

According to a survey, more than 40% of HIV-infected people are prone to malignant tumors, and cancer has gradually become the main cause of death among AIDS patients. So, can these patients with AIDS and cancer undergo stem cell transplantation?

② Stem cell transplant surgery is not as simple as imagined

For these five cured cases, we can say that we have found the target for treating AIDS, but there are still many difficulties in popularizing it to more people.

The first is the safety of stem cell transplantation. Before undergoing hematopoietic stem cell transplantation, patients must undergo intensive chemotherapy to clear out their original bone marrow hematopoietic system. This means that the patient's immune function is almost zero at this time, making it easy for various infections to occur. Even if the hematopoietic stem cell transplantation can be completed, there may be strong rejection, infection, and even death.

Second, the application of stem cell transplantation is limited. Allogeneic stem cell transplantation requires matching and is limited to patients with combined blood system tumors (various leukemias, multiple myeloma, and malignant lymphoma). As we mentioned earlier, two cured AIDS patients both suffered from blood system tumors. Their original intention of undergoing hematopoietic stem cell transplantation was to treat blood diseases. Fortunately, they found a suitable match. However, this is really difficult.

③ There are too few lucky people who have the CCR5-Δ32 gene mutation

There are more than 20,000 genes in the human body, and genes are composed of bases. The human body has 3 billion base pairs (half from the father and half from the mother), and each gene is composed of four bases arranged in ATCG. Due to the complexity of the organism itself, the length of the gene is not uniform and varies.

In the CCR5 gene, if 32 bases in the gene coding region are missing, the CCR5 gene cannot encode proteins normally, which becomes the so-called CCR5-Δ32 mutation. However, only the homozygous CCR5-Δ32 mutation from parents can fight HIV. However, there are too few people who carry the CCR5-Δ32 gene mutation. According to relevant research statistics, currently only about 1% of Caucasians (mainly Europeans) have this homozygous CCR5-Δ32 gene mutation. It is conceivable how difficult it is to find such a "lucky person" who is willing to donate bone marrow.

A report released by UNAIDS in 2023 shows that in 2022, there were 39 million people infected with HIV worldwide, of which 37.5 million were adults and 1.5 million were children under the age of 15. There is still a long way to go for mankind to completely conquer AIDS.

References:
[1] Zhang Z,Fu J,Xu X,etal.Safety and immunological responses to human
Mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients[J]. Aids, 2013, 27(8):1283-1293.

[2] Jiao Yanmei, Yang Hongge, Wang Fusheng. Progress and challenges in research on functional cure of AIDS[J]. Chinese Journal of AIDS and STDs, 2017, 23(1):92-93.

[3] Feilin. Double CCR5 gene mutation can prevent sexual transmission of HIV[J]. Foreign Medical Information, 1997, (22): 16.