Timothy Ray Brown

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Timothy Ray Brown
Timothy Ray Brown.jpg
Brown in 2012
Born(1966-03-11)March 11, 1966
DiedSeptember 29, 2020(2020-09-29) (aged 54)
NationalityAmerican
Known forFirst person cured of HIV/AIDS

Timothy Ray Brown (March 11, 1966 [1]  September 29, 2020) was an American considered to be the first person cured of HIV/AIDS. [2] [3] 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." [4] [2] [5]

Contents

Procedure

Timothy Ray Brown was born in Seattle, Washington, on March 11, 1966, and raised in the area by his single mother, Sharon, who worked for the King County sheriff's department. [6] [1] He journeyed across Europe as a young adult and was diagnosed with HIV in 1995 while studying in Berlin. [7] [4] In 2006, he was diagnosed with acute myeloid leukemia. On February 7, 2007, he underwent a procedure known as hematopoietic stem cell transplantation to treat leukemia [8] (performed by a team of doctors in Berlin, Germany, including Gero Hütter). From 60  matching donors, they selected a [CCR5]-Δ32 homozygous donor, an individual with two genetic copies of a rare variant of a cell surface receptor. This genetic trait confers resistance to HIV infection by blocking attachment of HIV to the cell. Roughly 10% of people of European or Western Asian ancestry have this inherited mutation, but it is rarer in other populations. [9] The transplant was repeated a year later after a leukemia relapse. Over the three years after the initial transplant, and despite discontinuing antiretroviral therapy, researchers could not detect HIV in Brown's blood or in various biopsies. [10] Levels of HIV-specific antibodies in Timothy Brown's blood also declined, suggesting that functional HIV may have been eliminated from his body. However, scientists studying his case warn that this remission of HIV infection is unusual. [11]

Brown, the "Berlin patient", suffered from serious transplant complications, graft-versus-host disease and leukoencephalopathy, which led researchers to conclude that the procedure should not be performed on others with HIV, even if sufficient numbers of suitable donors could be found. [12] [13]

Eleven years later, at the same conference, it was announced that it appeared that a second man had been cured. He was called "The London Patient", who later identified himself as Adam Castillejo. [14] He also received a bone marrow transplant to treat a cancer (Hodgkin's lymphoma) but was given weaker immunosuppressive drugs. The selected donor also carried the CCR5-Δ32 mutation. [15] [5]

As of 2017, six more people also appear to have been cleared of HIV after getting graft-versus-host disease; only one of them had received CCR5 mutant stem cells, leading researchers to conclude that when a transplant recipient has graft-versus-host disease, the transplanted cells may kill off the host's HIV-infected immune cells. [16]

Later life

In July 2012, Brown announced the formation of the Timothy Ray Brown Foundation in Washington, D.C., a foundation dedicated to fighting HIV/AIDS. [17] [18]

In September 2020, Brown revealed the leukemia that prompted his historic treatment had returned in 2019 and that he was terminally ill. Brown entered hospice care in Palm Springs, California, where he later died on September 29, 2020. [19] He was 54 years old.

See also

Related Research Articles

The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.

HIV-positive people, seropositive people or people who live with HIV are people infected with the human immunodeficiency virus (HIV), a retrovirus which if untreated may progress to acquired immunodeficiency syndrome (AIDS).

<span class="mw-page-title-main">Hematopoietic stem cell transplantation</span> Medical procedure to replace blood or immune stem cells

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 of a patient and to produce additional normal blood cells. It may be autologous, allogeneic or syngeneic.

<span class="mw-page-title-main">CCR5</span> Immune system protein

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.

This is a timeline of HIV/AIDS, including cases before 1980.

<span class="mw-page-title-main">2007 in science</span> Overview of the events of 2007 in science

The year 2007 involved many significant scientific events and discoveries, some of which are listed below.

<span class="mw-page-title-main">Maraviroc</span> Antiretroviral drug

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.

<span class="mw-page-title-main">Vicriviroc</span> Chemical compound

Vicriviroc, previously named SCH 417690 and SCH-D, is a pyrimidine CCR5 entry inhibitor of HIV-1. It was developed by the pharmaceutical company Schering-Plough. Merck decided to not pursue regulatory approval for use in treatment-experienced patients because the drug did not meet primary efficacy endpoints in late stage trials. Clinical trials continue in patients previously untreated for HIV.

Donor lymphocyte infusion (DLI) or buffy coat infusion is a form of adoptive immunotherapy used after hematopoietic stem cell transplantation.

Long-term nonprogressors (LTNPs), are individuals infected with HIV, who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load. Many of these patients have been HIV positive for 30 years without progressing to the point of needing to take medication in order not to develop AIDS. They have been the subject of a great deal of research, since an understanding of their ability to control HIV infection may lead to the development of immune therapies or a therapeutic vaccine. The classification "Long-term non-progressor" is not permanent, because some patients in this category have gone on to develop AIDS.

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.

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.

<span class="mw-page-title-main">HIV/AIDS research</span> Field of immunology research

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.

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%.

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.

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.

<span class="mw-page-title-main">Adam Castillejo</span> Second person known to have been cured of HIV infection

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.

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 resistant to most HIV strains. Edmonds ceased his HIV treatment in March 2021, with subsequent tests revealing no evidence of HIV in his body. Edmonds is among the five known individuals cured of HIV through stem cell transplantation for their blood cancer, alongside the Berlin Patient, London Patient, Düsseldorf Patient, and New York Patient.

References

  1. 1 2 "Timothy Ray Brown, 'Berlin patient' cured of HIV infection, dies at 54". Washington Post. Retrieved September 30, 2020.
  2. 1 2 Mary Engel (February 20, 2019). "Timothy Ray Brown: The accidental AIDS icon". Fred Hutch . Archived from the original on October 16, 2018. Retrieved March 4, 2015.
  3. Trudy Ring (September 7, 2012). "Is Anyone Immune to HIV?". HIVPlusMag. Archived from the original on March 9, 2016. Retrieved January 20, 2015.
  4. 1 2 Timothy Ray Brown (January 12, 2015). "I am the Berlin patient: a personal reflection". AIDS Research and Human Retroviruses. 31 (1): 2–3. doi:10.1089/aid.2014.0224. PMC   4287108 . PMID   25328084.
  5. 1 2 "berlin patient.pdf" (PDF). Dropbox. Archived (PDF) from the original on September 30, 2020. Retrieved May 8, 2020.
  6. Roberts, Sam (September 30, 2020). "Timothy Ray Brown, First Patient Cured of H.I.V., Dies at 54". The New York Times.
  7. "HIV patient Timothy Brown is the boy who lived". L.A. Times. June 5, 2011. Archived from the original on April 22, 2020. Retrieved September 30, 2020.
  8. "German HIV patient cured after stem cell transplant". Belfast Telegraph . December 15, 2010. Archived from the original on December 22, 2010. Retrieved December 15, 2010.
  9. "Bone marrow 'cures HIV patient'". BBC News. November 13, 2008. Archived from the original on January 7, 2009. Retrieved January 2, 2009.; Novembre, J; Galvani, AP; Slatkin, M (2005). "The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele". PLOS Biology. 3 (11): e339. doi: 10.1371/journal.pbio.0030339 . PMC   1255740 . PMID   16216086. Open Access logo PLoS transparent.svg
  10. Allers, K.; Hutter, G.; Hofmann, J.; Loddenkemper, C.; Rieger, K.; Thiel, E.; Schneider, T. (2010). "Evidence for the cure of HIV infection by CCR5 32/ 32 stem cell transplantation". Blood. 117 (10): 2791–2799. doi: 10.1182/blood-2010-09-309591 . PMID   21148083.
  11. "Web Exclusives : Transplanting Hope: Stem Cell Experiment Raises Eyebrows at CROI - by David Evans". Archived from the original on January 26, 2016. Retrieved January 21, 2015.
  12. Levy JA (2009). "Not an HIV Cure, but Encouraging New Directions". N Engl J Med. 360 (7): 724–725. doi:10.1056/NEJMe0810248. PMID   19213687. Archived from the original on February 15, 2009. Retrieved March 31, 2009.
  13. Lunzen, J.; Fehse, B.; Hauber, J. (2011). "Gene Therapy Strategies: Can We Eradicate HIV?". Current HIV/AIDS Reports. 8 (2): 78–84. doi:10.1007/s11904-011-0073-9. PMID   21331536. S2CID   43463970.
  14. Davis, Nicola (March 9, 2020). "Second person ever to be cleared of HIV reveals identity". The Guardian. Archived from the original on March 9, 2020. Retrieved March 10, 2020.
  15. Apoorva Mandavilli (March 4, 2019). "H.I.V. Is Reported Cured in a Second Patient, a Milestone in the Global AIDS Epidemic". The New York Times . Archived from the original on May 24, 2019. Retrieved March 4, 2019.
  16. Clare Wilson (May 6, 2017). "Immune war with donor cells after transplant may wipe out HIV". New Scientist. Archived from the original on December 8, 2018. Retrieved May 8, 2017.
  17. "Man "cured" of AIDS: Timothy Ray Brown". CBSNews. Archived from the original on June 12, 2018. Retrieved January 20, 2015.
  18. "Miraculous Activist". The Scientist Magazine®. Archived from the original on August 9, 2020. Retrieved May 8, 2020.
  19. Marilynn Marchione (September 25, 2020). "1st man cured of HIV infection now has terminal cancer". ABC News. Archived from the original on September 30, 2020. Retrieved September 25, 2020.; Mark S. King (September 25, 2020). "As Timothy Ray Brown faces death, a great love endures". Los Angeles Blade. Retrieved September 25, 2020.; "'The Berlin Patient': First person ever cured from HIV infection dies of cancer". www.abc.net.au. September 30, 2020. Archived from the original on September 30, 2020. Retrieved September 30, 2020.