The Berlin patient is an anonymous person from
Berlin
Berlin ( , ) is the capital and largest city of Germany by both area and population. Its 3.7 million inhabitants make it the European Union's most populous city, according to population within city limits. One of Germany's sixteen constitue ...
, Germany, who was described in 1998 as exhibiting prolonged "post-treatment control" of
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
viral load
Viral load, also known as viral burden, is a numerical expression of the quantity of virus in a given volume of fluid, including biological and environmental specimens. It is not to be confused with viral titre or viral titer, which depends on the ...
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
The Conference on Retroviruses and Opportunistic Infections (CROI) is an annual scientific meeting devoted to the understanding, prevention and treatment of HIV/AIDS and the opportunistic infection
An opportunistic infection is an infection cau ...
, where his cure was first announced, and because he lived in, and was treated in Berlin. This second "Berlin patient" chose to come forward and make his name,
Timothy Ray Brown
Timothy Ray Brown (March 11, 1966September 29, 2020) was an American considered to be the first person cured of HIV/AIDS. Brown was called "The Berlin Patient" at the 2008 Conference on Retroviruses and Opportunistic Infections, where his cure ...
, public in late 2010.
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
Adam Castillejo, also known as "The London Patient", is the second person known to have been cured of HIV infection.
His body became resistant to HIV infection after receiving a bone marrow transplant to treat Hodgkin's lymphoma. The donor carri ...
". The patient described made himself and his name,
Adam Castillejo
Adam Castillejo, also known as "The London Patient", is the second person known to have been cured of HIV infection.
His body became resistant to HIV infection after receiving a bone marrow transplant to treat Hodgkin's lymphoma. The donor carri ...
, public in March 2020. He also received a
bone marrow transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...
to treat a cancer (
Hodgkin's lymphoma
Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition wa ...
) but was given weaker immunosuppressive drugs. The selected donor also carried the
CCR5-Δ32
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.
In humans, the ''CCR5'' gene that encodes the CCR5 pr ...
mutation.
Cases
The first Berlin patient was described in 1998.
After receiving an experimental
therapy
A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis.
As a rule, each therapy has indications and contraindications. There are many different ...
, the patient, who has remained
anonymous
Anonymous may refer to:
* Anonymity, the state of an individual's identity, or personally identifiable information, being publicly unknown
** Anonymous work, a work of art or literature that has an unnamed or unknown creator or author
* Anonym ...
, has maintained low levels of
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
and has remained off
antiretroviral therapy
The management of HIV/AIDS normally includes the use of multiple Antiviral drug, antiretroviral drugs as a strategy to control HIV/AIDS, HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life- ...
.
The world-renowned "second" Berlin patient,
Timothy Ray Brown
Timothy Ray Brown (March 11, 1966September 29, 2020) was an American considered to be the first person cured of HIV/AIDS. Brown was called "The Berlin Patient" at the 2008 Conference on Retroviruses and Opportunistic Infections, where his cure ...
, 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. He received a
stem cell transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produc ...
from a donor naturally immune to HIV and has remained off
antiretroviral therapy
The management of HIV/AIDS normally includes the use of multiple Antiviral drug, antiretroviral drugs as a strategy to control HIV/AIDS, HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life- ...
since the first day of his stem cell transplant.
[ ]
Their stories were chronicled in the 2014 book, ''Cured: The People who Defeated HIV'' (2015) by
Nathalia Holt.
The Visconti Cohort, a group of fourteen patients who received early therapy for the virus (described in a scientific paper published in 2013
), 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. 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. 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.
Anonymous: the 1998 Berlin patient
The first Berlin patient was a German man in his mid-twenties.
He was a patient of Dr. Heiko Jessen in
Berlin, Germany
Berlin ( , ) is the capital and largest city of Germany by both area and population. Its 3.7 million inhabitants make it the European Union's most populous city, according to population within city limits. One of Germany's sixteen constituent ...
.
He was diagnosed with
acute
Acute may refer to:
Science and technology
* Acute angle
** Acute triangle
** Acute, a leaf shape in the glossary of leaf morphology
* Acute (medicine), a disease that it is of short duration and of recent onset.
** Acute toxicity, the adverse eff ...
HIV infection in 1995.
He was prescribed an unusual
combination therapy
Combination therapy or polytherapy is therapy that uses more than one medication or modality. Typically, the term refers to using multiple therapies to treat a ''single'' disease, and often all the therapies are pharmaceutical (although it can also ...
:
didanosine
Didanosine (ddI, DDI), sold under the brand name Videx, is a medication used to treat HIV/AIDS. It is used in combination with other medications as part of highly active antiretroviral therapy (HAART). It is of the reverse-transcriptase inhibitor ...
,
indinavir
Indinavir (IDV; trade name Crixivan, made by Merck) is a protease inhibitor used as a component of highly active antiretroviral therapy to treat HIV/AIDS. It is soluble white powder administered orally in combination with other antiviral drugs. Th ...
and
hydroxyurea
Hydroxycarbamide, also known as hydroxyurea, is a medication used in sickle-cell disease, essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, and cervical cancer. In sickle-cell disease it increases fetal hemoglobin and ...
.
Hydroxyurea was the most unusual of the three, as it is a
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
drug not approved by the U.S.
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) for HIV treatment. 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
HLA-B57 (B57) is an HLA- B serotype. B57 is a split antigen from the B17 broad antigen, the sister serotype B58. The serotype identifies the more common HLA-B*58 gene products. (For terminology help see: HLA-serotype tutorial.) Like B58, B57 i ...
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.
Timothy Ray Brown: the 2008 cured Berlin patient
The most famous Berlin patient is
Timothy Ray Brown
Timothy Ray Brown (March 11, 1966September 29, 2020) was an American considered to be the first person cured of HIV/AIDS. Brown was called "The Berlin Patient" at the 2008 Conference on Retroviruses and Opportunistic Infections, where his cure ...
. He is originally from
Seattle, Washington
Seattle ( ) is a port, seaport city on the West Coast of the United States. It is the county seat, seat of King County, Washington, King County, Washington (state), Washington. With a 2020 population of 737,015, it is the largest city in bo ...
. He was diagnosed with HIV in 1995 and began
antiretroviral therapy
The management of HIV/AIDS normally includes the use of multiple Antiviral drug, antiretroviral drugs as a strategy to control HIV/AIDS, HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life- ...
. In 2006, Brown was diagnosed with
acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may includ ...
(AML). His physician, Dr.
Gero Hütter
Gero Hütter (born 18 December 1968) is a German hematologist. Hütter and his medical team transplanted bone marrow deficient in a key HIV receptor to a leukemia patient, Timothy Ray Brown, who was also infected with human immunodeficiency virus ...
, at
Charité
The Charité – Universitätsmedizin Berlin (Charité – Berlin University of Medicine) is one of Europe's largest university hospitals, affiliated with Humboldt University and Free University Berlin. With numerous Collaborative Research Cen ...
Hospital in Berlin, arranged for him to receive a
hematopoietic stem cell transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...
from a donor with the "delta32"
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
on the
CCR5
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.
In humans, the ''CCR5'' gene that encodes the CCR5 pro ...
receptor.
This
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
, found at relatively high frequencies in Northern Europeans (16%), results in a mutated CCR5
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
. The majority of HIV cannot enter a human
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
without a functional CCR5
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. An exception to this is a small minority of
viruses
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
that use alternate
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
s, such as
CXCR4
C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the ''CXCR4'' gene. The protein is a CXC chemokine receptor.
Function
CXCR-4 is an alpha-chemokin ...
or
CCR2
C-C chemokine receptor type 2 (CCR2 or CD192 (cluster of differentiation 192) is a protein that in humans is encoded by the ''CCR2'' gene. CCR2 is a CC chemokine receptor.
Gene
This CCR2 gene is located in the chemokine receptor gene cluster ...
. Those individuals who are
homozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
for the CCR5 mutation are resistant to HIV and rarely progress to
AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual m ...
. Brown received two stem cell transplants from one donor
homozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
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
In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic ...
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
''The New England Journal of Medicine'' (''NEJM'') is a weekly medical journal published by the Massachusetts Medical Society. It is among the most prestigious peer-reviewed medical journals as well as the oldest continuously published one.
Hist ...
''.
As of 2011, Brown remains off antiretroviral therapy and is considered cured, although 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).
Timothy Ray Brown died on September 30, 2020, after a five-month battle with leukaemia.
See also
*
Mississippi baby
The Mississippi baby (born 2010) is a Mississippi girl who in 2013 was thought to have been cured of HIV. She had contracted HIV at birth from her HIV-positive mother. Thirty hours after the baby was born, she was treated with intense antiretro ...
*
Lulu and Nana controversy
The He Jiankui affair is a scientific and bioethical controversy concerning the use of genome editing following its first use on humans by Chinese scientist He Jiankui, who edited the genomes of human embryos in 2018. He became widely known on ...
*
Ravindra Gupta
Professor Ravindra "Ravi" Kumar Gupta is a professor of clinical microbiology at the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge. He is also a member of the faculty of the Africa Health Res ...
, doctor who treated the ''London Patient''.
References
{{DEFAULTSORT:Berlin Patient
1990s in science
2000s in science
1990s in Berlin
2000s in Berlin
HIV/AIDS in Germany
People with HIV/AIDS
Set index articles