The Berlin Patient

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, 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.^[4] 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. 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 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.^[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]

There is now doubt however that Timothy Brown's apparent cure was due to the unusual nature of the stem cells he received. As a result of the transplant he suffered graft-versus-host disease. Six more people seem (as of 2017) to have been freed of HIV after getting graft-versus-host disease, and only one of them had received CCR5 mutant stem cells. So it appears that when someone gets graft-versus-host disease the transplanted cells may kill off all the host's HIV-infected immune cells.^[17]

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.^[18]

See also

• Mississippi baby
• Nathalia Holt

References