A 53-year-old German man has been declared at least the third HIV-infected after surgery to replace bone marrow cells with HIV-resistant stem cells from a donor.
For many years, antiretroviral therapy (ART) has been given to HIV-infected people to reduce the virus to nearly undetectable levels and prevent it from infecting others. However, the immune system keeps the virus trapped in reservoirs in the body, and when an individual stops taking ART, the virus can begin replicating and spreading.
A real cure would eliminate this reservoir. This appears to have happened to the latest patient, whose name has not been released. I have not been infected with HIV since then.
Related stem cell technology was first used to treat Timothy Ray Brown, often referred to as the Berlin patient. In 2007, he underwent a bone marrow transplant that destroyed these cells and replaced them with stem cells from a healthy donor to treat acute myeloid leukemia. Brown’s treatment team selected a donor with a genetic mutation called CCR5Δ32/Δ32. This prevents the CCR5 cell surface protein from being expressed on the cell surface. Because HIV uses its proteins to enter immune cells, this mutation effectively makes the cells resistant to the virus. After the procedure, Brown was able to stop using his ART and he was HIV-free until his death in 2020.
In 2019, researchers revealed that London patient Adam Castillejo appeared to be cured with the same procedure. And in 2022, he announced that scientists thought a New York patient who had been HIV-free for 14 months could also be cured, but researchers said it would be impossible to confirm it. I warned you it was too early.
Ravindra Gupta, a microbiologist at the University of Cambridge, UK, who led the team that treated Castillejo, said the latest study “confirms the fact that CCR5 is currently the most tractable target to achieve therapy.” said.
low virus level
A patient in Düsseldorf had very low levels of HIV thanks to ART when he was diagnosed with acute myeloid leukemia. Cancerous myeloid cells were destroyed and replaced with stem cells from donors carrying the CCR5Δ32/Δ32 mutation.
Over the next five years, Jensen’s team took tissue and blood samples from patients. Years after the transplant, scientists continued to discover immune cells that specifically responded to HIV. It’s not clear whether these immune cells targeted active virus particles or the “graveyard” of viral debris, Jensen says. They also found her DNA and RNA of her HIV in the patient’s body, which never seemed to replicate.
To better understand how the transplant works, the team performed further tests, including transplanting the patient’s immune cells into mice engineered to have a human-like immune system. . The virus was unable to replicate in mice, suggesting it was non-functional. The final test was for the patient to discontinue her ART use. “This shows that it’s not impossible to clear her HIV from the body, it’s just very difficult,” says Jensen.
In a statement, the patient who underwent treatment said the bone marrow transplant had been a “very difficult road”, adding that he plans to dedicate part of his life to helping fund research.
Timothy Henrich, an infectious disease researcher at the University of California, San Francisco, says the study is very thorough. Several patients have been successfully treated with a combination of her ART and her HIV-resistant donor cells, making it very likely that these patients will achieve her HIV cure.
Gupta agrees, but adds that in some cases, viruses mutate in the body and enter cells in other ways. It’s also unclear whether the chemotherapy the patient received for cancer before the bone marrow transplant helped eliminate HIV by preventing infected cells from dividing, he says.
However, bone marrow replacement surgery is unlikely to be deployed in people who do not have leukemia. Because this procedure carries a high risk. In particular, an individual may reject the donor’s bone marrow. Several teams are testing the possibility of using stem cells taken from their own body and genetically engineered to carry the CCR5Δ32/Δ32 mutation. This eliminates the need for donor cells.
Jensen says his team used stem cells from donors with CCR5Δ32/Δ32 mutations to perform transplants for several other people affected by both HIV and cancer, but those individuals His team says that if HIV reservoirs are large at the time of transplantation, this will affect the recovery of the immune system and the body. We are planning to study whether it will eliminate the virus that remains in the body.
This article is reproduced with permission and was first published on February 21, 2023.
