▎WuXi AppTec Content Team Editor
“When I was HIV-infected in 1988, like everyone else at the time, I thought it was a death sentence. I never thought I’d be able to live to this day, finding my HIV free!”
Thanks to the progress of HIV drug development over the past three decades, HIV-infected people can now live a healthy lifespan similar to that of normal people as long as they take their medicines on time every day. The only option to accompany them. A man who has been living with HIV for more than 31 years has achieved long-term remission without the need to continue taking antiviral drugs after a stem cell transplant, researchers at the City of Hope Medical Center reported today. The 66-year-old patient is the fourth HIV patient in the world to be “cured” by this method, and the oldest HIV and blood cancer patient to be “cured” after a stem cell transplant,’ the press release noted.
Additionally, results of 15-year functional cure in a 74-year-old HIV female patient were reported today at the AIDS 2022 Annual Meeting Press Conference . These results offer hope for a “cure” of HIV infection.
Image source: 123RF
The man was treated with a stem cell transplant in 2019 when he was diagnosed with acute myeloid leukemia (AML), a more severe form of HIV in older HIV patients common leukemia. Stem cell transplantation is one of the common treatments for AML, and when treating this patient, the researchers specifically selected a donor with a rare genetic mutation. The mutation he carried in the gene encoding the CCR5 protein stopped the CCR5 protein from being expressed. CCR5 is a receptor on CD4-positive immune cells that the HIV virus uses to enter and multiply in immune cells. This CCR5 mutation blocks the way the HIV virus enters the cell, thereby preventing the HIV virus from replicating.
The potential of this strategy to “cure” HIV infection was first demonstrated more than a decade ago. At the 2008 International AIDS Congress, researchers reported the case of what was then called the “Berlin Patient,” an HIV-infected man named Timsy Ray Brown who developed AML at age 40, and who received CCR5 After a mutated stem cell transplant, no HIV was found in the blood, even after stopping antiviral drugs. He is the first HIV-infected person in the world to be “cured” using this strategy.
Image source: 123RF
Since then, two more people with HIV have been “cured” by receiving stem cell transplants with CCR5 mutations. Their case shows that the “cure” of AIDS is no longer an isolated case, and it also means that therapies developed based on CCR5 may have the potential to cure HIV infection. However, stem cell transplantation itself is a complex and high-risk treatment modality. It does not apply to ordinary HIV-infected patients, who are given the opportunity to receive stem cell transplants because of blood cancers.
The man reported today was 63 years old at the time of treatment and is therefore at higher risk for complications after a stem cell transplant. City of Hope researchers designed a reduced-intensity pre-transplant chemotherapy regimen that allowed him to achieve a complete remission of AML before transplant, while reducing the chance of post-transplant complications.
This patient received a stem cell transplant in 2019. The good news is that after receiving the treatment, not only did the AML get a complete remission, but the HIV virus did not come back. Now he’s been off antiviral drugs for over 17 months, and researchers haven’t found any signs of HIV replication in his body.
▲One of the study leaders, Dr. Jana K. Dickter, a clinical professor at City of Hope (Image source: Reference [2])
This patient’s outcome has profound implications for HIV treatment, said Dr. Jana K. Dickter, a clinical professor at City of Hope and one of the study leaders. “He was the eldest of (four) patients to receive stem cell transplantation, had the longest HIV history, and received the lowest intensity of immunosuppressive therapy. The evidence we obtained showed that if By being able to find suitable stem cell donors for HIV patients with blood cancers, we can use less intensive chemotherapy regimens to achieve the goal of dual remission. This provides new opportunities for older patients with both HIV and blood cancers opportunity.”
Because of the risks associated with stem cell transplantation, it is not a recommended treatment option for HIV patients who do not have blood cancers. However, industry experts say the results show that gene editing of cells in patients may become a cure in the future.Strategies to cure HIV infection. Earlier this year, a company called Excision BioTherapeutics had announced the launch of a Phase 1/2 clinical trial to test the potential of EBT-101, an in vivo gene-editing therapy developed based on CRISPR gene-editing technology, as a one-time treatment for HIV patients.
Another HIV patient reported at the AIDS 2022 Annual Meeting Press Conference was diagnosed with HIV at age 59. In 2006, she participated in a clinical trial where she received multiple immunomodulatory therapies alongside antiviral therapy to enhance the ability of immune cells to control the HIV virus. Trial results showed that her immune system had successfully controlled HIV levels for 15 years after stopping antiviral therapy. Although there was still a replicable HIV virus in her cells, her CD8-positive T cells and natural killer cells had a strong inhibitory effect on HIV. This case demonstrates the potential to effectively control HIV replication by enhancing the activity of immune cells in patients, and is expected to provide an innovative therapeutic development strategy.
“For HIV patients, it’s a signal of hope.” Professor Eileen Scully, Johns Hopkins University School of Medicine, told the Washington Post “This strategy works, and it has been validated again. It also shows that the scientific community is actively working to address this challenge,” the newspaper said in an interview.
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