Text/Wang Yuge, Ph.D. in Immunology, United States, Special Expert of CC Intelligence Bureau, Phoenix.com
Key Takeaways:
1. A study in the latest issue of the journal Nature revealed that a 60-year-old man with AIDS in Germany was cured of HIV through hematopoietic stem cell transplantation (HSCT). He was the seventh person in the world to be cured of AIDS and was called "the next Berlin patient". In 2009, the patient was diagnosed with AIDS. In 2015, he was diagnosed with acute myeloid leukemia as a cancer of the blood and bone marrow, which gave him a chance to be cured.
2. The first AIDS patient in the world to be cured was Timothy, the "Berlin Patient". After he was diagnosed with AIDS, he developed leukemia. The doctor recommended a stem cell transplant, and after 3 months of surgery, he was no longer able to detect HIV. At the end of 2007, his leukemia relapsed, he underwent a second stem cell transplant, and AIDS was completely cured. But he eventually died of leukemia in 2020.
3. In 2019, the "London patient" was cured after receiving a hematopoietic stem cell transplant; In 2022, the 66-year-old AIDS patient "City of Hope" was cured; In March 2023, Nature · Medicine reported on the cured "Düsseldorf patient". Many AIDS patients have been cured, but the treatment is difficult to promote, on the one hand, the cured patients are both AIDS and cancer patients, and on the other hand, bone marrow transplantation is a high-risk clinical operation. Hematopoietic stem cell transplantation is not the best cure for HIV, and more research is needed to obtain a more widespread treatment.
The world's 7th AIDS patient was cured! The seven cured patients were all AIDS and cancer patients
AIDS overcome?
A study in the latest issue of the journal Nature revealed that a 60-year-old man with AIDS in Germany, after receiving a stem cell transplant, began to stop taking antiretroviral drugs that suppress HIV in September 2018, and as of nearly 6 years since the study was submitted, the patient's viral load has not rebounded, and more importantly, the patient's HIV-1 antibody titer has gradually declined, and the HIV-specific T cell response has gradually disappeared, indicating that the patient has been "eradicated" (eradication).
At the 25th World AIDS Conference in Munich, Germany, at the end of July, he was called the seventh person in history to be cured of AIDS.
The patient, known as "the next Berlin patient", was also cured of HIV through hematopoietic stem cell transplantation (HSCT). It was done by a team of doctors and immunologist Professor Christian Gaebler from the Charité University Faculty of Medicine in Berlin (Universitätsmedizin Berlin). Coincidentally, 16 years ago, the world's first AIDS patient was cured: "Berlin Patient" Timothy Ray Brown ·· also treated by another treatment team at the hospital. The "Berlin patient" passed away in 2020 due to a recurrence of cancer.
In 2009, the "next Berlin patient" was diagnosed with AIDS. Unfortunately, in 2015, he was diagnosed with acute myeloid leukemia, a cancer of the blood and bone marrow. But it became a key to giving him a chance to be healed.
Before him, there were six AIDS patients, all of whom were later diagnosed with leukemia and cured by receiving stem cell transplants. Crucially, with the exception of the sixth Geneva patient, the stem cells transplanted by the remaining five people, including the "next Berlin patient" disclosed this time, all contain a rare genetic mutation - CCR5-delta32.
▎免疫学家Christian Gaebler
But unlike the above patients, Christian Gaebler, an immunologist and physician of the "next Berlin patient", said in the report: "I found a female donor with only one mutated copy similar to the 'next Berlin patient' while I could not find a stem cell matching donor with mutations in both copies of the CCR5 gene." ”
In 2015, the "next Berlin patient" underwent a stem cell transplant. In less than a month, the patient's bone marrow stem cells were replaced by donor stem cells.
As of Aug. 1, nearly six years later, researchers still couldn't find any evidence of HIV replication in patients.
This AIDS patient is the patient who has not rebounded for the longest time among the current HIV cured cases, and the mechanism of this patient's cure is actually the four mechanisms that I have repeatedly said: 1. CCR5Δ32 gene; 2. Myeloablative chemotherapy (chemotherapy before hematopoietic stem cell transplantation); 3. HSCT (hematopoietic stem cell transplantation); 4. GvHD (graft-versus-host disease).
This may provide a new treatment option for people with AIDS in the future.
"Berlin Patient": The world's first person cured of AIDS, who died of a recurrence of cancer ten years later
United States Timothy Ray Brown was the first person in the world to be cured of AIDS. This is a miracle 26 years after the first discovery of AIDS in June 1981.
In 1995, Timothy contracted AIDS while in Berlin, and after receiving antiretroviral therapy (ART), his AIDS was successfully controlled for 10 years. Unfortunately, in 2006, he was diagnosed with a fatal form of acute myeloid leukemia (AML). This is a type of blood cancer.
Timothy's doctor, Gero Hütter, specializes in leukemia and has no experience in treating HIV. The goal of his treatment was to treat leukemia rather than HIV, so Timothy immediately underwent chemotherapy. He spent four rounds of chemotherapy in recurrent infections and recovery, and his leukemia was indeed in remission.
It wasn't until late 2006 that his leukemia relapsed. Dr. Gero Hütter recommended a stem cell transplant with a low survival rate and high surgical costs. The bone marrow cells with HIV and cancer were completely eliminated from the body, and after 61 experiments, a bone marrow match carrying the CCR5 gene mutation was successfully found. CCR5 is the receptor for HIV virus to invade and infect human cells, and after the CCR5 Δ32/Δ32 gene mutation, cells lack CCR5 receptor, and HIV virus cannot be infected.
For leukemia patients infected with HIV, cancer cells are first killed by chemotherapy, and transplantation of hematopoietic stem cells with CCR5 gene mutations may cure leukemia while making the HIV virus in the patient's body infectable, so as to gradually clear the HIV virus and achieve long-term remission or even cure of AIDS.
On February 6, 2007, the day Timothy received his bone marrow transplant in Berlin, Germany, stopped his HIV medication. He also received radiation therapy before the bone marrow transplant to destroy his own bone marrow, which produces cancer cells. Three months after the bone marrow transplant, the doctor was no longer able to detect HIV in his blood! Timothy has since become the world's first person to be cured of HIV, but he has been referred to as the "Berlin Patient" for reasons of privacy. But when he returned to the United States for Christmas in late 2007, leukemia made a comeback after contracting pneumonia again.
In February 2008, Timothy had to receive a second stem cell transplant from the same donor. However, recovering from the second transplant was so difficult that Timothy almost lost her sight and speech, as well as the ability to walk. However, he stopped taking medication after receiving a bone marrow transplant, and after 3 months, he was undetectable in his body. That is, Timothy was once again completely cured. "The Berlin Patient", Timothy's legendary codename, has been around for many years. Subsequently, Timothy founded an organization called the AIDS Healing Coalition. He made his name public in 2010. However, it was his leukemia that ultimately led to his death.
On October 1, 2020, Timothy Ray Brown, the world's first HIV cured person, passed away at ·· age 54. This is a miracle in the history of AIDS, and it will not be repeated until nine years later.
▎Timothy was interviewed by the media at the International AIDS Conference.
"The London Patient", "City of Hope", "The Düsseldorf Patient", "The New York Patient", "The Geneva Patient", ...... There have been seven people who have been cured of AIDS
In 2019, a study published in the journal Nature showed that an HIV-infected patient known as the "London Patient" went into sustained remission of HIV infection after receiving hematopoietic stem cell transplant therapy for lymphoma, and even after stopping taking antiviral drugs, no signs of HIV recurrence were found in the subsequent 18 months.
Subsequently, the authors changed the assessment of the condition of "London patients" published in Nature after CCR5-Δ32 hematopoietic stem cell transplantation from "remission" to "cure".
There are currently two types of HIV cures, radical cures and functional cures. The traditional "cure" has only happened to one patient before, the "Berlin Patient" Timothy · Ray · Brown. However, the current academic community believes that the reason for the radical cure is that he has undergone two CCR5delta32 bone marrow transplants, so he has received two myeloablative chemotherapy, and has two graft-versus-host reactions (GvHD) at the same time.
The second cured case, reported in the journal Nature, was published by Gupta, School of Medicine, University of London, United Kingdom.
The HIV patient who underwent CCR5delta32 bone marrow transplantation for Hodgkin lymphoma quickly became homozygous for donor and developed mild GvHD, stopped his antiviral drugs 16 months after receiving the bone marrow transplant and did not rebound the virus for the 18th month. The gold standard assay (VOA method), which reflects the size of the viral repository, did not detect any complete viral reservoir components in the patient.
More importantly, the patient's HIV antibody titers gradually decreased, and eventually seronegative turned negative, a phenomenon that occurred for the second time after the Berlin patient. The patient's HIV-specific T cell response also faded. So far, the London patient has not relapsed, and is the second patient in history to be cured. Subsequently, gene editing therapy using CCR5 receptors to treat both "patients with cancer and AIDS" became almost a replica of the miracle cure.
In 2022, a 66-year-old AIDS patient, the City of Hope, was cured. He was diagnosed with HIV-1 in 1988, then developed leukemia and was off antiretroviral drugs for more than 17 months after a bone marrow transplant in 2019, with doctors finding no signs of HIV-1 replication. The patient is also the oldest patient to be cured of AIDS to date.
On March 16, 2023, the world's first HIV woman + minority patient treated with stem cell transplant was cured. She was called the "New York Patient".
In February last year, United Kingdom monthly journal Nature · Medicine reported on the fifth AIDS patient who had been cured. The 53-year-old man was diagnosed with acute myeloid leukemia in January 2011 and received a bone marrow transplant at the University Hospital in Düsseldorf, Germany, in 2013 using hematopoietic stem cells from a female donor. The AIDS patient, known as the "Düsseldorf patient", received a stem cell transplant about 10 years ago, and no active HIV virus was detected in his body four years after he stopped taking anti-HIV drugs.
▎ The London patient's name is Adam Castillejo. The New York Times reported that after more than a decade of grueling treatment and moments of despair, he chose to make his story public in March 2020, hoping to become an "ambassador of hope" for other AIDS patients.
The "Geneva patient" was the sixth patient to be reported, also undergoing a bone marrow stem cell transplant without the CCR5-delta32 mutation, which was first disclosed in 2023. It is still under observation.
CCR5 is a major entry point for HIV to attack the human body. Researchers believe that the replacement of immune cells with cells without CCR5 receptors through stem cell transplantation may be the reason why HIV does not rebound in patients after drug treatment is stopped.
Can this treatment be scaled up to more people living with HIV?
One important thing that these cured AIDS patients have in common is that when they are infected with AIDS, they also develop cancer, and most of them have leukemia. This means that if these treatments are to be scaled up, it may be necessary for people with AIDS to also be cancer patients. It is also necessary to find a match for the CCR5 gene mutation.
Over the years, researchers around the world have tried similar things with many other patients, but none of them have been successful. Bone marrow transplantation is also a high-risk clinical procedure, with hematopoietic stem cell transplantation itself carrying a 15% risk of death, even in the modern already highly optimized bone marrow transplant process.
At the same time, not all CCR5Δ32/Δ32 hematopoietic stem cell transplants are curable. In February this year, the University of Illinois at Chicago (UIC) reported a case of rapid rebound of the virus and treatment failure after 2 months of discontinuation of CCR5Δ32/Δ32 stem cell transplantation.
Therefore, the very high-risk CCR5Δ32/Δ32 HSCT (hematopoietic stem cell) transplant is not the best cure for HIV. It is believed that there will continue to be cases of HIV cures in the future. However, more research is needed to apply to a wider range of people living with HIV/AIDS.