Paul Edmonds |
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Paul Edmonds, is an American recognized as the oldest individual to achieve remission from both HIV and leukemia. He is known as the "City of Hope Patient" from the hospital where he underwent treatment in Duarte, California. Diagnosed with HIV in 1988 at the age of 33, Edmonds spent over three decades living with the virus until 2018, when he faced a new challenge—a diagnosis of myelodysplastic syndrome, evolving into acute myelogenous leukemia. His journey to recovery, culminating in a stem cell transplant in 2019, at age 63, involved a donor with a rare genetic mutation (homozygous CCR5 Delta 32) resistant to most HIV strains. Edmonds ceased his HIV treatment in March 2021, with subsequent tests revealing no evidence of HIV in his body. [1] [2] [3] [4] [5] Edmonds is among the five known individuals cured of HIV through stem cell transplantation for their blood cancer, alongside the Berlin Patient, [6] [7] London Patient, [8] Düsseldorf Patient, [9] and New York Patient. [10]
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce additional normal blood cells. HSCT may be autologous, syngeneic, or allogeneic.
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.
Cord blood is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders such as cancer.
Maraviroc, sold under the brand names Selzentry (US) and Celsentri (EU), is an antiretroviral medication used to treat HIV infection. It is taken by mouth. It is in the CCR5 receptor antagonist class.
Juvenile myelomonocytic leukemia (JMML) is a rare form of chronic leukemia that affects children, commonly those aged four and younger. The name JMML now encompasses all diagnoses formerly referred to as juvenile chronic myeloid leukemia (JCML), chronic myelomonocytic leukemia of infancy, and infantile monosomy 7 syndrome. The average age of patients at diagnosis is two (2) years old. The World Health Organization has included JMML as a subcategory of myelodysplastic and myeloproliferative disorders.
Donor lymphocyte infusion (DLI) or buffy coat infusion is a form of adoptive immunotherapy used after hematopoietic stem cell transplantation.
Gero Hütter is a German hematologist. Hütter and his medical team transplanted bone marrow deficient in a key HIV receptor to a leukemia patient, Timothy Ray Brown, who was also infected with human immunodeficiency virus (HIV). Subsequently, the patient's circulating HIV dropped to undetectable levels. The case was widely reported in the media, and Hütter was named one of the "Berliners of the year" for 2008 by the Berliner Morgenpost, a Berlin newspaper.
Timothy Ray Brown was an American considered to be the first person cured of HIV/AIDS. Brown was called "The Berlin Patient" at the 2008 Conference on Retroviruses and Opportunistic Infections, where his cure was first announced, in order to preserve his anonymity. He chose to come forward in 2010. "I didn't want to be the only person cured," he said. "I wanted to do what I could to make [a cure] possible. My first step was releasing my name and image to the public."
The Berlin patient is an anonymous person from Berlin, Germany, who was described in 1998 as exhibiting prolonged "post-treatment control" of HIV viral load after HIV treatments were interrupted.
HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.
Graft-versus-tumor effect (GvT) appears after allogeneic hematopoietic stem cell transplantation (HSCT). The graft contains donor T cells that can be beneficial for the recipient by eliminating residual malignant cells. GvT might develop after recognizing tumor-specific or recipient-specific alloantigens. It could lead to remission or immune control of hematologic malignancies. This effect applies in myeloma and lymphoid leukemias, lymphoma, multiple myeloma and possibly breast cancer. It is closely linked with graft-versus-host disease (GvHD), as the underlying principle of alloimmunity is the same. CD4+CD25+ regulatory T cells (Treg) can be used to suppress GvHD without loss of beneficial GvT effect. The biology of GvT response is still not fully understood but it is probable that the reaction with polymorphic minor histocompatibility antigens expressed either specifically on hematopoietic cells or more widely on a number of tissue cells or tumor-associated antigens is involved. This response is mediated largely by cytotoxic T lymphocytes (CTL) but it can be employed by natural killers as separate effectors, particularly in T-cell-depleted HLA-haploidentical HSCT.
Letermovir is an antiviral drug for the treatment of cytomegalovirus (CMV) infections. It has been tested in CMV infected patients with allogeneic stem cell transplants and may also be useful for other patients with a compromised immune system such as those with organ transplants or HIV infections. The drug was initially developed by the anti-infective division at Bayer, which became AiCuris Anti-infective Cures AG through a spin-out and progressed the development to end of Phase 2 before the project was sold to Merck & Co for Phase 3 development and approval.
A small proportion of humans show partial or apparently complete innate resistance to HIV, the virus that causes AIDS. The main mechanism is a mutation of the gene encoding CCR5, which acts as a co-receptor for HIV. It is estimated that the proportion of people with some form of resistance to HIV is under 10%.
David G. Maloney is an oncologist and researcher at Fred Hutchinson Cancer Research Center and the University of Washington who specializes in developing targeted immunotherapies for the treatment of blood cancers.
T-cell depletion (TCD) is the process of T cell removal or reduction, which alters the immune system and its responses. Depletion can occur naturally or be induced for treatment purposes. TCD can reduce the risk of graft-versus-host disease (GVHD), which is a common issue in transplants. The idea that TCD of the allograft can eliminate GVHD was first introduced in 1958. In humans the first TCD was performed in severe combined immunodeficiency patients.
Since antiretroviral therapy requires a lifelong treatment regimen, research to find more permanent cures for HIV infection is currently underway. It is possible to synthesize zinc finger nucleotides with zinc finger components that selectively bind to specific portions of DNA. Conceptually, targeting and editing could focus on host cellular co-receptors for HIV or on proviral HIV DNA.
Shimon Slavin is an Israeli professor of medicine. He pioneered immunotherapy mediated by allogeneic donor lymphocytes and innovative methods for stem cell transplantation to cure hematological malignancies and solid tumors. He also used hematopoietic stem cells to induce transplantation tolerance to bone marrow and organ allografts.
Chen Hu was a Chinese military physician and stem cell researcher. He served as Director of the PLA Institute of Hematopoietic Stem Cell Research and the Beijing Hematopoietic Stem Cell Therapy Laboratory. Known for his research on hematopoietic stem cell therapy for leukemia, he was awarded the State Science and Technology Progress Award in 2015 and the Ho Leung Ho Lee Prize in 2016. In 2017, he and Deng Hongkui engineered resistance to HIV in mice using CRISPR gene editing, and for the first time used the technique on an AIDS patient. He died of a sudden heart attack before their findings were published.
Deng Hongkui is a Chinese immunologist and stem cell researcher. He is a Changjiang Professor, the Boya Chair Professor, and Director of the Institute of Stem Cell Research at Peking University. He was awarded US$1.9 million by the Bill & Melinda Gates Foundation for his research on vaccines for HIV and hepatitis C. In 2017, he and Chen Hu engineered resistance to HIV in mice using CRISPR gene editing, and for the first time used the technique on an AIDS patient.
Adam Castillejo, also known as "The London Patient", is the second person known to have been cured of HIV infection. Castillejo, who is British-Venezuelan and has mixed European ancestry, lives in London. He has previously worked as a chef and is now a motivational speaker.