The Berlin Patient

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Anonymous
Born Germany
Occupation the Berlin patient: 1998
Timothy Ray Brown
Born USA
Occupation the Berlin patient: 2008

The Berlin patient is a phrase that has been used on two distinct and unrelated occasions to describe a person who has received a functional cure for HIV in Berlin, Germany. The first Berlin patient, who we now know is not cured, was described in 1998.[1] After receiving an experimental therapy, the patient, who has remained anonymous, has maintained at low levels of HIV and has remained off antiretroviral therapy.[2][3] The first patient is no longer considered to be cured of HIV and the lower levels of HIV detectable in his blood are likely because he has the HLA B*57 allele associated HIV replication control.[4] The world renowned "second" Berlin patient, Timothy Ray Brown, was first described in 2008 following a poster presented at the CROI 2008 Conference in Boston by Dr. Gero Hütter.[5] He received a stem cell transplant from a donor naturally resistant to HIV and has remained off antiretroviral therapy since the first day of his stem cell transplant. Timothy Ray Brown is thought to be the first and only person in the world cured of HIV.[6]

[7]

Anonymous: the 1998 Berlin patient[edit]

The first Berlin patient was a German in his mid-twenties.[3] He was a patient of Dr. Heiko Jessen in Berlin, Germany.[1][3] He was diagnosed with acute HIV infection in 1996.[1] He was prescribed an unusual combination therapy: didanosine, indinavir and hydroxyurea.[3] 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.[8] The combination was part of a small trial Dr. Jessen was testing in patients during acute HIV infection.[1] After several treatment interruptions, the patient went off the prescribed therapy completely.[3] The virus became almost undetectable.[3] The patient has remained off antiretroviral therapy.[3] In 2014 a follow-up report in NEJM suggest that the patient most likely controlled HIV because of the genetic background and not because of the particular treatment he received during acute HIV infection.[2] He is no longer considered to be cured of HIV because he has a detectable viral load likely controlled by the genetic mutation he has.[4]

Timothy Ray Brown: the 2008 cured Berlin patient[edit]

The most famous Berlin patient is Timothy Ray Brown. He is originally from Seattle, Washington.[9] He was diagnosed with HIV in 1995 and began antiretroviral therapy. In 2006, Timothy 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 CCR5 delta32 mutation.[10] This mutation, found at relatively high frequencies in Northern Europeans, results in a mutated CCR5 protein.[11] 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.[12] Those individuals who are homozygous for the CCR5 mutation are resistant to HIV and rarely progress to AIDS. Timothy received two stem cell transplants from one donor homozygous for the delta32 mutation: one in 2007 and one in 2008.[10] Timothy stopped taking his antretroviral therapy 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.[10] Today, Timothy still remains off antiretroviral therapy and is considered cured.[13][14][15] Today leading HIV cure scientists agree that Timothy has what is called a sterilizing cure as opposed to a functional cure. In 2012, Timothy Ray Brown announced the formation of an organization whose sole purpose is to find a cure for AIDS called the Cure for AIDS Coalition. The first project of the Cure for AIDS Coalition is the Cure Report launched on October 16, 2014 during the NIH Strategies for an HIV Cure meeting held in the Washington, DC area.[16]

Cure Research studies inspired by Timothy Ray Brown, the Berlin Patient[edit]

Scientists around the world agree that all cure for HIV related research studies today was inspired by the remarkable case of Timothy Ray Brown, the Berlin Patient. In fact, on December 2, 2013, President Obama announced during a speech commemorating World AIDS Day; "Today I’m pleased to announce a new initiative at the National Institutes of Health to advance research into an HIV cure. We’re going to redirect $100 million into this project to develop a new generation of therapies. Because the United States should be at the forefront of new discoveries into how to put HIV into long-term remission without requiring lifelong therapies -- or, better yet, eliminate it completely."[17] Some of the HIV cure research today inspired by the case of Timothy Ray Brown focus on gene therapy and early treatment.[18][19][20] and HIV eradication and early therapy[21][22]

See also[edit]

References[edit]

  1. ^ a b c d Schoofs, Mark (June 21, 1998). "The Berlin Patient". New York Times Magazine. 
  2. ^ a b Jessen, Heiko; Allen, Todd M.; Hendrik, Streeck (13 February 2014). "How a Single Patient Influenced HIV Research — 15-Year Follow-up". The New England Journal of Medicine 370: 682–683. doi:10.1056/NEJMc1308413. Retrieved 15 July 2014. 
  3. ^ a b c d e f g "Control of HIV despite the Discontinuation of Antiretroviral Therapy". New England Journal of Medicine. 1999. doi:10.1056/NEJM199905273402114. 
  4. ^ a b Jefferys, Richard (13 February 2014). "Update Published on the First Berlin Patient". Treatment Action Group. Archived from the original on 15 July 2014. Retrieved 15 July 2014. 
  5. ^ Schoofs, Mark. "A Doctor, a Mutation and a Potential Cure for AIDS". Wall Street Journal. 
  6. ^ "How Many People Have Been Cured of HIV, One". 
  7. ^ Mejia, Paula (13 July 2014). "Supposedly Cured H.I.V. Patient Still Has the Virus". Newsweek. Archived from the original on 15 July 2014. Retrieved 15 July 2014. 
  8. ^ "Hydroxyurea in the treatment of HIV-1". The Annals of Pharmacotherapy. 2011. 
  9. ^ Doughton, Sandi (July 17, 2013). "‘I don’t want to be only person cured of HIV’". Seattle Times. 
  10. ^ a b c "Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation". New England Journal of Medicine 360 (7): 692–8. 2009. doi:10.1056/NEJMoa0802905. PMID 19213682. 
  11. ^ "The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele". PLoS Biology. 2005. doi:10.1371/journal.pbio.0030339. 
  12. ^ "The biology of CCR5 and CXCR4". Current Opinion in HIV and AIDS. 2009. doi:10.1097/COH.0b013e328324bbec. 
  13. ^ Rosenberg, Tina (May 29, 2011). "The Man Who Had HIV and Now Does Not". New York Magazine. 
  14. ^ Pollack, Andrew (November 28, 2011). "New Hope of a Cure for H.I.V.". 
  15. ^ "Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation". Blood. 2011. doi:10.1182/blood-2010-09-309591. PMID 21148083. 
  16. ^ "Cure Report". 
  17. ^ "President Obama directs $100 million toward Cure for HIV". 
  18. ^ "Hematopoietic-Stem-Cell-Based Gene Therapy for HIV Disease". Cell Stem Cell. 2011. doi:10.1016/j.stem.2011.12.015. 
  19. ^ "Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo". Nature Biotechnology 28 (8). 2010. doi:10.1038/nbt.1663. 
  20. ^ "Novel Cell and Gene Therapies for HIV". Cold Spring Harbor Perspectives in Medicine. 2012. doi:10.1101/cshperspect.a007179. 
  21. ^ "Drug brings HIV out of hiding". Nature. 2012. doi:10.1038/nature.2012.10180. 
  22. ^ "2012 AIDS meeting: Early treatment is key, experts say". July 24, 2012.