The Berlin Patient
Anonymous | |
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Born | Germany |
Occupation | the Berlin patient: 1998 |
Timothy Ray Brown | |
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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] though some debate exists whether there is no trace of the virus in his body (a "sterilizing" cure) or whether he simply no longer needs treatment (a "functional" cure).[16]
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.[17]
See also
References
- 1 2 3 4 Schoofs, Mark (June 21, 1998). "The Berlin Patient". New York Times Magazine.
- ↑ 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.
- 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.
- ↑ Schoofs, Mark. "A Doctor, a Mutation and a Potential Cure for AIDS". Wall Street Journal.
- 1 2 Ledford, Heidi (10 July 2014). "HIV rebound dashes hope of 'Mississippi baby' cure". Nature.
- ↑ "Making Sense of the Three Types of HIV Cure: The Berlin Patient, the Mississippi Child, and the VISCONTI Cohort". Retrieved 23 May 2015.
- ↑ "Hydroxyurea in the treatment of HIV-1". The Annals of Pharmacotherapy. 34: 89–93. 2011. doi:10.1345/aph.19004.
- ↑ Migueles, SA; Laborico, AC; Imamichi, H; Shupert, WL; Royce, C; McLaughlin, M; Ehler, L; Metcalf, J; Liu, S; Hallahan, CW; Connors, M (2003). "The differential ability of HLA B*5701+ long-term nonprogressors and progressors to restrict human immunodeficiency virus replication is not caused by loss of recognition of autologous viral gag sequences". J. Virol. 77: 6889–98. doi:10.1128/jvi.77.12.6889-6898.2003. PMC 156173. PMID 12768008.
- ↑ Doughton, Sandi (July 17, 2013). "'I don't want to be only person cured of HIV'". Seattle Times.
- 1 2 3 Hütter, G; Nowak, D; Mossner, M; et al. (2009). "Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation". New England Journal of Medicine. 360 (7): 692–8. doi:10.1056/NEJMoa0802905. PMID 19213682.
- ↑ Novembre, J; Galvani, AP; Slatkin, M (2005). "The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele". PLoS Biology. 3: e339. doi:10.1371/journal.pbio.0030339. PMC 1255740. PMID 16216086.
- ↑ Alkhatib, G (2009). "The biology of CCR5 and CXCR4". Current Opinion in HIV and AIDS. 4: 96–103. doi:10.1097/COH.0b013e328324bbec. PMC 2718543. PMID 19339947.
- ↑ Rosenberg, Tina (May 29, 2011). "The Man Who Had HIV and Now Does Not". New York Magazine.
- ↑ Pollack, Andrew (November 28, 2011). "New Hope of a Cure for H.I.V.".
- ↑ Allers, K; Hütter, G; Hofmann, J; et al. (2011). "Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation". Blood. 117: 2791–2799. doi:10.1182/blood-2010-09-309591. PMID 21148083.
- ↑ Knox, Richard (June 13, 2012). "Traces Of Virus In Man Cured Of HIV Trigger Scientific Debate". NPR News. Retrieved December 1, 2016.
- ↑ "Cure Report".