See also
- Mississippi baby
- Lulu and Nana controversy
- Ravindra Gupta, doctor who treated the London Patient
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.
The phrase "Berlin patient" was later used to preserve the anonymity of a different individual claimed to have been functionally cured of HIV infection, when his case was presented at the 2008 Conference on Retroviruses and Opportunistic Infections, where his cure was first announced, and because he resided and was treated in Berlin. This second "Berlin patient" chose to come forward and make his name, Timothy Ray Brown, public in late 2010. [1] [2]
Eleven years later, nearly on the same date, at the same conference, it was announced that it appeared that a third man had been cured; he was called the "London Patient". The patient described made himself and his name, Adam Castillejo, public in March 2020. [3] 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. [4]
The first Berlin patient was described in 1998. [5] After receiving an experimental therapy, the patient, who has remained anonymous, has maintained low levels of HIV and has remained off antiretroviral therapy. [6] [7]
The world-renowned "second" Berlin patient, Timothy Ray Brown, had a bone marrow transplant on February 7, 2007, to cure his leukemia, and hopefully his HIV. The results of the procedure were presented by Dr. Gero Hütter at the CROI 2008 Conference in Boston. [8] He received a stem cell transplant from a donor naturally immune to HIV and has remained off antiretroviral therapy since the first day of his stem cell transplant. [9]
Their stories were chronicled in the 2014 book, Cured: The People who Defeated HIV (2015) by Nathalia Holt. [10] The Visconti Cohort, a group of fourteen patients who received early therapy for the virus (described in a scientific paper published in 2013 [11] ), were considered to be in "long-term virological remission," meaning that they still harbor the virus within their bodies but HIV viral loads are low or undetectable despite being off antiretroviral therapy. [12] At least two Visconti cohort members have since restarted antiretroviral therapy; in one case due to increasing viral load and CD4 T cell count decline, and in another case due to a cancer diagnosis. Another cohort member is displaying clear evidence of declining CD4 T cell counts over time. This information was revealed in the last two slides of a presentation given by Asier Sáez-Cirión at the International AIDS Society's Towards an HIV Cure Symposium in 2015. [13] Timothy Ray Brown is the only individual who is considered to have a sterilizing cure, meaning there is strong evidence that he no longer harbors infectious HIV virus within his body.[ citation needed ]
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The first Berlin patient was a German man in his mid-twenties. [7] He was a patient of Dr. Heiko Jessen in Berlin, Germany. [5] [7] He was diagnosed with acute HIV infection in 1995. [5] He was prescribed an unusual combination therapy: didanosine, indinavir and hydroxyurea. [7] Hydroxyurea was the most unusual of the three, as it is a cancer drug not approved by the U.S. Food and Drug Administration (FDA) for HIV treatment. [14] The combination was part of a small trial Dr. Jessen was testing in patients during acute HIV infection. [5] After several treatment interruptions, the patient went off the prescribed therapy completely. [7] The virus became almost undetectable. [7] The patient has remained off antiretroviral therapy. [7] In 2014 a follow-up report in NEJM concludes "a likely explanation for control of viral replication in this patient is genetic background, regardless of intervention," although this point is still under debate. [6] The NEJM update reports that the individual possesses the HLA-B*57 allele which has been associated with HIV control, and a large proportion of CD8 T cell responses targeting HIV are restricted by HLA-B*57.[ citation needed ]
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The most famous Berlin patient is Timothy Ray Brown. He is originally from Seattle, Washington. [15] He was diagnosed with HIV in 1995 and began antiretroviral therapy. In 2006, Brown was diagnosed with acute myeloid leukemia (AML). His physician, Dr. Gero Hütter, at Charité Hospital in Berlin, arranged for him to receive a hematopoietic stem cell transplant from a donor with the "delta32" mutation on the CCR5 receptor. [16] This mutation, found at relatively high frequencies in Northern Europeans (16%), results in a mutated CCR5 protein. [17] The majority of HIV cannot enter a human cell without a functional CCR5 gene. An exception to this is a small minority of viruses that use alternate receptors, such as CXCR4 or CCR2. [18] Those individuals who are homozygous for the CCR5 mutation are resistant to HIV and rarely progress to AIDS. Brown received two stem cell transplants from one donor homozygous for the delta32 mutation: one in 2007 and one in 2008. [16] Brown stopped taking his antiretroviral medication on the day of his first transplant. Three months after the first stem cell transplant, levels of HIV rapidly plummeted to undetectable levels while his CD4 T cell count increased. In addition, blood and tissue samples from areas of the body where HIV is known to hide were tested. The results were published in the New England Journal of Medicine . [16] As of 2011, Brown remained off antiretroviral therapy and was considered cured, [19] [20] [21] although some debate exists whether there was no trace of the virus in his body (a "sterilizing" cure) or whether he simply no longer needed treatment (a "functional" cure). [22]
Timothy Ray Brown died on September 30, 2020, after a five-month battle with leukaemia. [23]
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.
The spread of HIV/AIDS has affected millions of people worldwide; AIDS is considered a pandemic. The World Health Organization (WHO) estimated that in 2016 there were 36.7 million people worldwide living with HIV/AIDS, with 1.8 million new HIV infections per year and 1 million deaths due to AIDS. Misconceptions about HIV and AIDS arise from several different sources, from simple ignorance and misunderstandings about scientific knowledge regarding HIV infections and the cause of AIDS to misinformation propagated by individuals and groups with ideological stances that deny a causative relationship between HIV infection and the development of AIDS. Below is a list and explanations of some common misconceptions and their rebuttals.
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).
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.
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.
Infection with HIV, a retrovirus, can be managed with treatment but without treatment can lead to a spectrum of conditions including AIDS.
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.
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.
Françoise Barré-Sinoussi is a French virologist and Director of the Regulation of Retroviral Infections Division and Professor at the Institut Pasteur in Paris, France. Born in Paris, France, Barré-Sinoussi performed some of the fundamental work in the identification of the human immunodeficiency virus (HIV) as the cause of AIDS. In 2008, Barré-Sinoussi was awarded the Nobel Prize in Physiology or Medicine, together with her former mentor, Luc Montagnier, for their discovery of HIV. She mandatorily retired from active research on August 31, 2015, and fully retired by some time in 2017.
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.
CCR5 receptor antagonists are a class of small molecules that antagonize the CCR5 receptor. The C-C motif chemokine receptor CCR5 is involved in the process by which HIV, the virus that causes AIDS, enters cells. Hence antagonists of this receptor are entry inhibitors and have potential therapeutic applications in the treatment of HIV infections.
AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs) are an investigational class of antiretroviral drugs used to treat Human Immunodeficiency Virus (HIV) infection. Unlike other antiretroviral agents given to reduce viral replication, AV-HALTs are single or combination drugs designed to reduce the rate of viral replication while, at the same time, also directly reducing the state of immune system hyperactivation now believed to drive the loss of CD4+ T helper cells leading to disease progression and Acquired Immunodeficiency Syndrome (AIDS).
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."
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%.
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.
Sarah Fidler is an immunologist, researcher and professor in HIV Medicine at Imperial College London and consultant physician in HIV for St Mary's Hospital, London.
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.
