Berlin Patient
{{Short description|German patients cured of HIV}}
{{about|the original 1998 Berlin Patient|the case of the 2008 Berlin patient|Timothy Ray Brown|the Australian podcast|The Berlin Patient (podcast)}}
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.{{Cite journal |author=Timothy Ray Brown |title=I am the Berlin patient: a personal reflection |journal=AIDS Research and Human Retroviruses |volume=31 |issue=1 |pages=2–3 |date=January 12, 2015 |pmid=25328084 |doi=10.1089/aid.2014.0224|pmc=4287108 }}{{Cite web |title=Timothy Ray Brown: The accidental AIDS icon |author=Mary Engel |work=Fred Hutch |date=February 20, 2019 |access-date=March 4, 2015 |url= https://www.fredhutch.org/en/news/center-news/2015/02/aids-icon-timothy-ray-brown.html }}
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.{{cite journal |last1=Cohen |first1=Jon |title=Second 'cured' HIV patient goes public |journal=Science |date=9 March 2020 |url=https://www.science.org/content/article/second-cured-hiv-patient-goes-public |accessdate=2 April 2020 |language=en}} 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.{{cite news |url=https://www.nytimes.com/2019/03/04/health/aids-cure-london-patient.html |title=H.I.V. Is Reported Cured in a Second Patient, a Milestone in the Global AIDS Epidemic |newspaper=The New York Times |date=March 4, 2019 |author=Apoorva Mandavilli |author-link=Apoorva Mandavilli |accessdate=March 4, 2019}}
Cases
The first Berlin patient was described in 1998.{{cite news|last=Schoofs|first=Mark | name-list-style = vanc |title=The Berlin Patient|url=https://www.nytimes.com/1998/06/21/magazine/the-berlin-patient.html|newspaper=New York Times Magazine|date=June 21, 1998}} After receiving an experimental therapy, the patient, who has remained anonymous, has maintained low levels of HIV and has remained off antiretroviral therapy.{{cite journal | vauthors = Jessen H, Allen TM, Streeck H | title = How a single patient influenced HIV research – 15-year follow-up | journal = The New England Journal of Medicine | volume = 370 | issue = 7 | pages = 682–83 | date = February 2014 | pmid = 24521131 | pmc = 4264571 | doi = 10.1056/NEJMc1308413 }}{{cite journal | vauthors = Lisziewicz J, Rosenberg E, Lieberman J, Jessen H, Lopalco L, Siliciano R, Walker B, Lori F | title = Control of HIV despite the discontinuation of antiretroviral therapy | journal = The New England Journal of Medicine | volume = 340 | issue = 21 | pages = 1683–84 | date = May 1999 | pmid = 10348681 | doi = 10.1056/NEJM199905273402114 | doi-access = free }}
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.{{cite news|last=Schoofs|first=Mark | name-list-style = vanc |title=A Doctor, a Mutation and a Potential Cure for AIDS|url=https://www.wsj.com/articles/SB122602394113507555|newspaper=Wall Street Journal}} 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.{{cite book| title=Cured: The People Who Defeated HIV|url=https://books.google.com/books?id=qjaNDQAAQBAJ|year= 2015|publisher=Penguin Publishing Group|isbn=978-0-14-218184-3}} {{OCLC|937872774}}
Their stories were chronicled in the 2014 book, Cured: The People who Defeated HIV (2015) by Nathalia Holt.{{cite news|last1=Johnson|first1=George | name-list-style = vanc |title=Patients and Fortitude 'Cured,' by Nathalia Holt|url=https://www.nytimes.com/2014/05/11/books/review/cured-by-nathalia-holt.html|access-date=7 May 2018|work=The New York Times|date=May 9, 2014}} The Visconti Cohort, a group of fourteen patients who received early therapy for the virus (described in a scientific paper published in 2013{{cite journal | vauthors = Sáez-Cirión A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, Potard V, Versmisse P, Melard A, Prazuck T, Descours B, Guergnon J, Viard JP, Boufassa F, Lambotte O, Goujard C, Meyer L, Costagliola D, Venet A, Pancino G, Autran B, Rouzioux C | display-authors = 6 | title = Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study | journal = PLOS Pathogens | volume = 9 | issue = 3 | pages = e1003211 | date = March 2013 | pmid = 23516360 | pmc = 3597518 | doi = 10.1371/journal.ppat.1003211 | doi-access = free }}), 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.{{cite web|url=http://www.amfar.org/articles/around-the-world/treatasia/2013/making-sense-of-the-three-types-of-hiv-cure--the-berlin-patient,-the-mississippi-child,-and-the-visconti-cohort/|title=Making Sense of the Three Types of HIV Cure: The Berlin Patient, the Mississippi Child, and the VISCONTI Cohort|access-date=23 May 2015|archive-date=18 May 2015|archive-url=https://web.archive.org/web/20150518065315/http://www.amfar.org/articles/around-the-world/treatasia/2013/making-sense-of-the-three-types-of-hiv-cure--the-berlin-patient,-the-mississippi-child,-and-the-visconti-cohort/|url-status=dead}} 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.{{Cite web|url=http://www.iasociety.org/Web/WebContent/File/HIV_Cure_Symposium_2015/Day2/Presentations/OA4-4-Saez-Cirion.pdf|title=HIV-1 virological remission for more than 12 years after interruption of early initiated antiretroviral therapy in a perinatally-infected child|last=Sáez-Cirión|first=Asier|name-list-style=vanc|date=July 19, 2015|website=International AIDS Society's Towards an HIV Cure Symposium|access-date=June 1, 2018|archive-date=November 12, 2018|archive-url=https://web.archive.org/web/20181112064441/https://www.iasociety.org/Web/WebContent/File/HIV_Cure_Symposium_2015/Day2/Presentations/OA4-4-Saez-Cirion.pdf|url-status=dead}} 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.{{cn|date=September 2022}}
Anonymous: the 1998 Berlin patient
{{Infobox person
|name=Anonymous
|birth_place=Germany
|death_date=
|death_place=
}}
The first Berlin patient was a German man in his mid-twenties. He was a patient of Dr. Heiko Jessen in Berlin, Germany. He was diagnosed with acute HIV infection in 1995. He was prescribed an unusual combination therapy: didanosine, indinavir and hydroxyurea. 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.{{cite journal | vauthors = Gibbs MA, Sorensen SJ | title = Hydroxyurea in the treatment of HIV-1 | journal = The Annals of Pharmacotherapy | volume = 34 | issue = 1 | pages = 89–93 | date = January 2000 | pmid = 10669190 | doi = 10.1345/aph.19004 | s2cid = 8198851 | url = http://www.theannals.com/content/34/1/89.long | archive-url = https://archive.today/20130816023657/http://www.theannals.com/content/34/1/89.long | url-status = dead | archive-date = 2013-08-16 | url-access = subscription }} The combination was part of a small trial Dr. Jessen was testing in patients during acute HIV infection. After several treatment interruptions, the patient went off the prescribed therapy completely. The virus became almost undetectable. The patient has remained off antiretroviral therapy. 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. 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.{{cn|date=September 2022}}
Timothy Ray Brown: the 2008 cured Berlin patient
{{Infobox person
|name=Timothy Ray Brown
| birth_date = 1966
|birth_place=United States
|death_date=
|death_place=
}}
The most famous Berlin patient is Timothy Ray Brown. He is originally from Seattle, Washington.{{cite news|last=Doughton|first=Sandi | name-list-style = vanc |title='I don't want to be only person cured of HIV'|url=http://seattletimes.com/html/localnews/2021212371_aidscurexml.html|newspaper=Seattle Times|date=July 17, 2013}} 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.{{cite journal | vauthors = Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K, Schneider T, Hofmann J, Kücherer C, Blau O, Blau IW, Hofmann WK, Thiel E | title = Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation | journal = The New England Journal of Medicine | volume = 360 | issue = 7 | pages = 692–98 | date = February 2009 | pmid = 19213682 | doi = 10.1056/NEJMoa0802905 | s2cid = 14905671 | url = http://pdfs.semanticscholar.org/1926/c7c57edd48d6a3714280e2c57d7e9039285e.pdf | archive-url = https://web.archive.org/web/20190219183009/http://pdfs.semanticscholar.org/1926/c7c57edd48d6a3714280e2c57d7e9039285e.pdf | url-status = dead | archive-date = 2019-02-19 }} This mutation, found at relatively high frequencies in Northern Europeans (16%), results in a mutated CCR5 protein.{{cite journal | vauthors = Novembre J, Galvani AP, Slatkin M | title = The geographic spread of the CCR5 Delta32 HIV-resistance allele | journal = PLOS Biology | volume = 3 | issue = 11 | pages = e339 | date = November 2005 | pmid = 16216086 | pmc = 1255740 | doi = 10.1371/journal.pbio.0030339 | doi-access = free }} {{open access}} 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.{{cite journal | vauthors = Alkhatib G | title = The biology of CCR5 and CXCR4 | journal = Current Opinion in HIV and AIDS | volume = 4 | issue = 2 | pages = 96–103 | date = March 2009 | pmid = 19339947 | pmc = 2718543 | doi = 10.1097/COH.0b013e328324bbec }} 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. 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. As of 2011, Brown remained off antiretroviral therapy and was considered cured,{{cite news|last=Rosenberg|first=Tina | name-list-style = vanc |title=The Man Who Had HIV and Now Does Not|url=http://nymag.com/health/features/aids-cure-2011-6/|newspaper=New York Magazine|date=May 29, 2011}}{{cite news|last=Pollack|first=Andrew | name-list-style = vanc |title=New Hope of a Cure for H.I.V.|work=The New York Times |url=https://www.nytimes.com/2011/11/29/health/new-hope-of-a-cure-for-hiv.html|date=November 28, 2011}}{{cite journal | vauthors = Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T | title = Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation | journal = Blood | volume = 117 | issue = 10 | pages = 2791–99 | date = March 2011 | pmid = 21148083 | doi = 10.1182/blood-2010-09-309591 | url = http://bloodjournal.hematologylibrary.org/content/117/10/2791.long | doi-access = free | url-access = subscription }} 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).{{cite news |title=Traces Of Virus In Man Cured Of HIV Trigger Scientific Debate |date=June 13, 2012 |first=Richard |last=Knox | name-list-style = vanc |publisher=NPR News |access-date=December 1, 2016 |url=https://www.npr.org/sections/health-shots/2012/06/13/154869103/traces-of-virus-in-man-cured-of-hiv-trigger-scientific-debate}}
Timothy Ray Brown died on September 30, 2020, after a five-month battle with leukaemia.{{Cite news|url=https://www.bbc.co.uk/news/health-54355673|title=Berlin patient: First person cured of HIV, Timothy Ray Brown, dies|work=BBC News|date=30 September 2020}}
See also
{{Portal|Viruses}}
- Mississippi baby
- Lulu and Nana controversy
- Ravindra Gupta, doctor who treated the London Patient
References
{{Reflist|30em}}
{{Authority control}}
{{HIV/AIDS}}
{{DEFAULTSORT:Berlin Patient}}