The fourth person who has been “cured” of AIDS may have appeared. How far is humanity from conquering AIDS? (Part 2)

Produced by: Science Popularization China

Author: Lu Xiuyuan (Researcher at Osaka University's Immunology Research Center)

Producer: China Science Expo

Recently, according to a research report, a 66-year-old leukemia patient has achieved long-term remission of AIDS after receiving a stem cell transplant, or has been "cured", becoming the fourth AIDS patient in the world to be declared "cured". This is the fourth case of AIDS being cured through stem cell transplantation after the "Berlin Patient", "London Patient" and "New York Patient", and is also the oldest patient at present.

In the previous article, we have discussed in detail why AIDS is difficult to cure and the situation of the "Berlin patient", the first case to be declared "cured". Today, let’s take a look at the latest "City of Hope" case!

"City of Hope", success after a long wait

With the first case of cure of the "Berlin patient", doctors were confident that they would repeat this miracle, but for various reasons, no miracle happened again for a long time.

Afterwards, whether it was the second "London patient" who was cured or the current "City of Hope" patient, their cure methods were actually in line with the cure method of the "Berlin patient".

The City of Hope patient was diagnosed with AIDS in 1988. He has been taking antiviral therapy for more than 30 years to control his disease. In 2018, the patient was diagnosed with acute myeloid leukemia (AML), a cancer of the blood and bone marrow.

He was scheduled to undergo a stem cell transplant to treat his leukemia, and his doctors first gave him less intensive chemotherapy, followed by a hematopoietic stem cell transplant using cells from a donor carrying a rare genetic mutation. This mutation, called "homozygous CCR5 delta 32," can make its carriers resistant to HIV by changing the entry point the virus normally uses to invade the body's white blood cells.

Hematopoietic stem cell transplantation is an improved treatment that is easier for older people with AML to accept and reduces the likelihood of transplant-related complications. It is also the method that cured the "Berlin patient."

In March 2021, doctors stopped the antiviral treatment of this "City of Hope" patient. Before the 24th International AIDS Conference (AIDS 2022) held on July 29, 2022, the treatment team said that there had been no signs of HIV replication in his body for more than a year. It can be said that this case provides the possibility of treatment for elderly patients with AIDS and blood cancer.

As Sharon Lewin, president-elect of the International AIDS Society, said, the case provides "continued hope and inspiration" for people living with HIV and the wider scientific community. However, due to the risks involved in the surgery, it is unlikely to be an option for most people living with HIV.

Scientists believe the process works because the donor's stem cells have a specific, rare genetic mutation that means they lack the receptor that HIV uses to infect cells.

However, it should be noted that after being cured, not all traces of HIV are erased. Generally, some cells in the patient's body still contain HIV gene fragments hidden in the cell nucleus, but these dormant genes are like fossils and can no longer cause trouble.

CCR5 receptor protein on the cell membrane, author: Thomas Splettstoesser

There are already cases of cure, can this therapy be applied on a large scale?

Although there have been successful cases, treating AIDS through bone marrow transplantation is still an experimental therapy that has not been tested on a large scale.

Bone marrow transplantation itself is a very dangerous operation. The test subjects may not survive due to cancer, infection and other reasons. Nowadays, taking drugs can suppress HIV virus and maintain normal life of infected people, taking risks in bone marrow transplantation is not in line with the principle of maximizing the interests of patients. Therefore, the test subjects can only be those patients who are infected with HIV and suffer from terminal blood system cancer like the Berlin patient, London patient and "City of Hope" patients.

In addition, since natural CCR5 mutations are extremely rare in the population, it is very difficult for the test subjects mentioned above to find a suitable CCR5 mutant bone marrow donation, which greatly limits the application of this experimental therapy.

So why can't hematopoietic stem cells be genetically edited to acquire the CCR5 mutation?

Although gene editing technology is now quite mature and has also appeared in some blood cancer treatment programs such as CAR-T, hematopoietic stem cells can hardly be cultured and proliferated in vitro, and they can easily lose their stem cell characteristics and differentiate into other types of cells, thus losing their value for transplantation. Therefore, gene editing of hematopoietic stem cells is still very difficult, and using gene editing to create CCR5 mutations to treat AIDS is currently difficult to achieve.

Gene editing art illustration, source: Freepik.com

However, science and technology are advancing at a rapid pace, and some of the latest research has given us hope of overcoming difficulties. Although there is still a long way to go from theoretical discovery to clinical application, I believe that in the near future, the nightmare of AIDS will become history.

References:

https://mp.weixin.qq.com/s/KngdehInM8WzGVKVG7ZXxg

https://www.nytimes.com/2020/03/09/health/london-patient-hiv-castillejo-takeaways.html

"Long-termcontrolofHIVbyCCR5Delta32/Delta32stem-celltransplantation".TheNewEnglandJournalofMedicine.360(7):692–98.