AIDS "cured" after stem cell transplantation, the third case in the world may appear!

▎WuXi AppTec Content Team Editor In 2013, a middle-aged woman from New York was diagnosed with HIV infection when she was still in the early stages of infection
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She began treatment immediately, and her viral load was quickly brought under control to undetectable levels
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But fate presented her with another problem
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In 2017, she was diagnosed with acute myeloid leukemia (AML)
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As a last resort for a cure for the blood tumor, she received a stem cell transplant -- which carries a key mutation in the CCR5 gene that makes the body immune to HIV
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After 27 months, she stopped all anti-HIV therapy
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So far, HIV has not been detected in her body for 14 consecutive months
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Image source: 123RF local time on February 15th, at the CROI (Conference on Retroviruses and Opportunistic Infections) 2022 annual meeting, Dr.
Yvonne Bryson, director of pediatric infectious diseases at the University of California, Los Angeles (UCLA) School of Medicine, reported this heavy case.

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This means that, after the "Berlin patient" and the "London patient", the "New York patient" will be the third lucky person to achieve AIDS "cure" through stem cell transplantation if he can continue to stop taking the drug and has no signs of HIV infection.

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The research team pointed out in the report of the CROI meeting that it is worth noting that, unlike the first two cures, the "New York patient" was the first female transplant cure, and was also a minority (CCR5 mutation carriers were mostly white), and adopted cord blood transplant
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Her case also suggests that strategies based on this mutation have the potential to offer hope to a wider range of patients
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The same key CCR5 gene HIV specifically attacks CD4-positive lymphocytes in the human body, proliferates in the lymphocytes, and then destroys the lymphocytes, resulting in cell lysis, thereby continuing to infect and destroy other lymphocytes
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In addition to CD4, chemokine receptor 5 (CCR5, a protein receptor on the surface of leukocytes) is one of two co-receptors for HIV entry into cells, and some HIV strains enter lymphocytes Requires binding to CCR5 on the cell surface
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The gene mutation CCR5Δ32/Δ32 causes CC5 to not be expressed, which is equivalent to locking the door and preventing HIV from invading lymphocytes
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Some people are born with the CCR5Δ32/Δ32 mutation (homozygous carriers), which makes them almost immune to HIV
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Such groups are unusually rare, accounting for only 1% of people of Nordic descent
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In addition, 10%-18% of people of European descent carry a Δ32 mutation, which does not prevent infection, but reduces the risk of infection and delays AIDS progression
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In 2007, HIV-infected "Berlin patient" Timothy Ray Brown received a bone marrow transplant for AML from a CCR5Δ32/Δ32 mutation
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After the transplant recovered, even without medication, the HIV level in Timsey's blood remained extremely low and could not replicate
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At the 2008 International AIDS Conference, researchers reported on the case of Timsey, who became the world's first cured AIDS patient
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Image source: 123RF Nearly ten years later, the "London patient" with a similar fate has entered people's sight
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"London Patient" Adam Castillejo has both AIDS and refractory Hodgkin lymphoma
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He underwent a stem cell transplant in 2016, and the bone marrow transplant donor he received also carried the CCR5Δ32/Δ32 gene mutation
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Adam stopped antiretroviral therapy 16 months after the transplant
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Long-term follow-up results published in The Lancet HIV in 2020 showed that 30 months after stopping the drug, the "London patient" still had no active viral infection detected in the blood
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Adam is believed to be the second AIDS patient in the world to be cured
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His case shows that AIDS cure is no longer an isolated case, and it also means that therapies based on CCR5 may have the potential to cure HIV infection
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The emergence of the "New York patient" provides further insights into curing HIV infection
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"New York Patient" Difference: Bone Marrow Transplant + Umbilical Cord Blood Transplant "New York Patient" received stem cell transplants as a "combination gift" - stem cells from her relative's bone marrow and umbilical cord from a blood bank blood
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Among them, this cord blood sample carried the CCR5Δ32/Δ32 mutation that confers HIV immunity
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In other words, doctors performed both a bone marrow transplant and an umbilical cord blood transplant for her
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"This allows for accelerated growth of stem cells until the umbilical cord blood 'takes over'," Dr.
Yvonne Bryson said in a presentation at the CROI meeting
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"Berlin patient" and "London patient" had stem cells from bone marrow transplants
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Bone marrow transplants are usually more difficult than umbilical cord blood transplants, which are often used to treat childhood cancers
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After the transplant, the patient's immune system began to use The stem cells derived from the bone marrow transplant were reconstituted, and she did not develop "graft-versus-host disease" (GVH), a common side effect of stem cell transplants
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The
surgery went well and the patient was even discharged early
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Over time, the umbilical cord The proportion of cells in the blood transplant gradually increased
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After 100 days, stem cells from the umbilical cord blood had "taken over" her immune system
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More than a year after the transplant, her CD4 immune cells returned to normal levels
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At 27 months, she decided to stop All HIV treatments to see if transplant is effective against HIV immunity
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Time for the real test
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Image credit: 123RF Over time, except for a brief detection of HIV DNA at 12 weeks, researchers have never tested it in patients since then to HIV viral load, including CD4+ T cells and bone marrow
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"It has been 14 months now and she has not rebounded
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Dr.
Yvonne Bryson pointed out
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In addition, her antibody test was negative
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The research team even cultivated another 75 million cells in the laboratory based on her cells, and also found no trace of HIV infection
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More exploration Of course, the researchers are equally cautious look at this case
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For example, after receiving a stem cell transplant, this woman not only carried a CCR5 mutation, but also accidentally carried a CXCR4 mutation, and the CXCR4 receptor is also one of the "side doors" that HIV can walk when it infects cells
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For example, except that HIV was not detected in the blood, what was the test result in the tissue? There is a lack of information on this issue
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For another example, why did this patient not develop common GVH after transplantation? "There has long been a hypothesis that at some point the body may need GVH to help clear CD4+ T cells, whether or not those cells carry replication-competent viruses
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" The National Allergy and Dr.
Carl Dieffenbach, director of the AIDS Division at the National Institute of Infectious Diseases (NIAID), pointed out, "But she doesn't have GVH, which is incredible
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" .
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In addition, how to move from a single case to a cure for more AIDS patients is also a follow-up face.
challenge
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Luis Montaner, director of the Laboratory of Immunopathology at the Wistar Institute in Philadelphia, said the case "supports a therapeutic strategy for editing CCR5 through CRISPR Cas9 technology
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Looking forward to the enlightenment from the cases of these lucky people, which can bring hope for more HIV-infected people to be cured
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Related reading "The Lancet" sub-issue: 30 months of drug withdrawal, what does the world's second AIDS cure mean? The second case in the world: no need for drug treatment, self-healing of AIDS is not a special case! Research is expected to bring new therapy NEJM: 40% lower risk of treatment failure! AIDS "Children's Drugs" Ushered in an Important Breakthrough "Nature-Medicine": A single drug can suppress HIV for up to half a year, and the Phase 1 trial of "Elite Neutralizing Antibodies" is published to eliminate HIV transmission one step closer, and preventive drugs reduce the infection rate 92%! "The Lancet" sub-journal published real-world data reference materials of 10,000 people (you can slide up and down to view) [1] Bryson Y et al.
HIV-1 remission with CCR5∆32/∆32 haplo-cord transplant in a US woman.
CROI 2022, Oral abstract 65.
https://ww2.
aievolution.
com/cro2201/index.
cfm?do=abs.
viewAbs&abs=3310[2] A Third Person Living With HIV Has Been Cured by Transplant.
Retrieved February 16, 2022 from https:// CROI 2022: Potential HIV cure case in a US woman using donor cord stem cells.
Retrieved February 16, 2022 from https://i-base.
info/htb /42182[4] Gupta RK, et al.
, (2020).
Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report.

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