The Berlin Patient

Anonymous
Born Germany
Occupation the Berlin patient: 1998
Timothy Ray Brown
Born United States
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/AIDS in Berlin, Germany. The first Berlin patient was described in 1998.[1] After receiving an experimental therapy, the patient, who has remained anonymous, has maintained low levels of HIV and has remained off antiretroviral therapy.[2][3] 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.[4] 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. Their stories were chronicled in the 2014 book, Cured: The People who Defeated HIV.[5] The Visconti Cohort, a group of fourteen patients who received early therapy for the virus, are considered functionally cured of HIV, meaning that they still harbor the virus within their bodies but do not need to take antiretroviral therapy.[6] A child known as the Mississippi baby was once considered part of this elite group but has since suffered a relapse.[5] Timothy Ray Brown is the only individual who is considered to have a sterilizing cure, meaning he no longer harbors the HIV virus within his body.

Anonymous: the 1998 Berlin patient

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 1995.[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 J.A. Food and Drug Administration (FDA) for HIV treatment.[7] 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 suggests that the patient's genetic background may have contributed to his control of the virus although this point is still under debate. The patient has an HLA-B57 allele which has been associated with HIV nonprogressors, however the majority of those with this genetic background are unable to control the virus.[8] Because of this, the cause of his control of the virus is still unknown.

Timothy Ray Brown: the 2008 cured Berlin patient

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 "delta 32" mutation on the CCR5 receptor.[10] This mutation, found at relatively high frequencies in Northern Europeans (16%), 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 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.[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

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][21] HIV eradication and early therapy.[22][23]

See also

References

  1. 1 2 3 4 Schoofs, Mark (June 21, 1998). "The Berlin Patient". New York Times Magazine.
  2. ↑ 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. 1 2 3 4 5 6 7 "Control of HIV despite the Discontinuation of Antiretroviral Therapy". New England Journal of Medicine 340: 1683. 1999. doi:10.1056/NEJM199905273402114.
  4. ↑ Schoofs, Mark. "A Doctor, a Mutation and a Potential Cure for AIDS". Wall Street Journal.
  5. 1 2 http://www.nature.com/news/hiv-rebound-dashes-hope-of-mississippi-baby-cure-1.15535. Missing or empty |title= (help); External link in |website= (help);
  6. ↑ "Making Sense of the Three Types of HIV Cure: The Berlin Patient, the Mississippi Child, and the VISCONTI Cohort". 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/. External link in |website= (help);
  7. ↑ "Hydroxyurea in the treatment of HIV-1". The Annals of Pharmacotherapy 34: 89–93. 2011. doi:10.1345/aph.19004.
  8. ↑ http://www.ncbi.nlm.nih.gov/pubmed/12768008. Missing or empty |title= (help); External link in |website= (help);
  9. ↑ Doughton, Sandi (July 17, 2013). "‘I don’t want to be only person cured of HIV’". Seattle Times.
  10. 1 2 3 "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 3: e339. 2005. doi:10.1371/journal.pbio.0030339.
  12. ↑ "The biology of CCR5 and CXCR4". Current Opinion in HIV and AIDS 4: 96–103. 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 117: 2791–2799. 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 10: 137–147. 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): 839–847. 2010. doi:10.1038/nbt.1663.
  20. ↑ "Novel Cell and Gene Therapies for HIV". Cold Spring Harbor Perspectives in Medicine 2: a007179. 2012. doi:10.1101/cshperspect.a007179.
  21. ↑ "Progress in Gene Therapy for HIV Cure". February 22–25, 2016.
  22. ↑ "Drug brings HIV out of hiding". Nature. 2012. doi:10.1038/nature.2012.10180.
  23. ↑ "2012 AIDS meeting: Early treatment is key, experts say". July 24, 2012.
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