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. After
receiving an experimental therapy, the patient, who has remained anonymous, has
maintained low levels of HIV and has remained off antiretroviral therapy. 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. 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. 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. A child known
as the Mississippi baby was once considered part of this elite group but
has since suffered a relapse. 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. He was a patient of
Dr. Heiko Jessen in Berlin, Germany. He was diagnosed with acute HIV infection
in 1995. He was prescribed an unusual combination therapy: didanosine,
indinavir and hydroxyurea. Hydroxyurea was the most unusual of the three, as it
is a cancer drug not approved by the U.S. Food and Drug Administration 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 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 am 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. 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. He was diagnosed
with HIV in 1995 and began antiretroviral therapy. In 2006, Timothy
was diagnosed with acute myeloid leukemia. 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. This mutation, found at relatively high frequencies in
Northern Europeans, results in a mutated CCR5 protein. 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. 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. 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. Today, Timothy still remains off antiretroviral
therapy and is considered cured. 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. 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." Some of the
HIV cure research today inspired by the case of Timothy Ray Brown focus on gene
therapy and early treatment, HIV eradication and early therapy.
See also Mississippi baby
References