Gero Hütter
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Gero Hütter (born 18 December 1968) is a German
hematologist Hematology (American and British English spelling differences#ae and oe, always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to ...
. Hütter and his medical team transplanted bone marrow deficient in a key HIV receptor to a
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
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 ...
, who was also infected with
human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the ...
(HIV). Subsequently, the patient's circulating HIV dropped to undetectable levels. The case was widely reported in the media, and Hütter was named one of the "Berliners of the year" for 2008 by the ''Berliner Morgenpost'', a Berlin newspaper.


HIV treatment

In 2009, Hütter, Eckhard Thiel and others from the Charité Hospital in
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 Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...
, published a report on the case in the ''New England Journal of Medicine''. Their patient Timothy Ray Brown, a
US citizen Citizenship of the United States is a legal status that entails Americans with specific rights, duties, protections, and benefits in the United States. It serves as a foundation of fundamental rights derived from and protected by the Constituti ...
born in Seattle, Washington, and living in Berlin, had both
acute myelogenous 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) and HIV. The physicians found a bone marrow donor with a
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 in both genomic copies of a gene encoding a cell-surface
chemokine receptor Chemokine receptors are cytokine receptors found on the surface of certain cells that interact with a type of cytokine called a chemokine. There have been 20 distinct chemokine receptors discovered in humans. Each has a rhodopsin-like 7-trans ...
called
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 p ...
. Because "most of HIV strains" use the CCR5 receptor to enter a host cell, the mutation confers resistance to HIV infection. The patient himself was heterozygous for CCR5-Δ32. Following the transplant procedure, the patient's CD4+ T-cells circulating in the blood were homozygous for CCR5-Δ32. The
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s in his bowel, which continued to express wildtype CCR5 (because they hadn't been replaced yet from bone marrow precursors), also had no detectable virus. After 600 days without antiretroviral drug treatment, the patient's blood, bone marrow and bowel HIV levels were below the limit of detection; the virus was thought to be present in other tissues. However, the patient actually had a brain biopsy, in addition to biopsies of his intestines, liver, lymph nodes, bone marrow—basically, every part of the body that can be biopsied. All were negative for virus. There is no virus in this person's body out to two and a half years off of all anti-HIV drugs. His antibody levels—called titers—are declining just the way expected if the patient was vaccinated against HIV and then the levels of antibodies were examined. They'd be very strong in the beginning, but would weaken if they are not re-exposed to the virus. It is believed this patient has no HIV in his body and therefore there is nothing to re-expose him, so the concentration of HIV antibodies in his blood is decreasing. It is predicted that, in a couple of years, his HIV antibody test will be negative. The mortality risk associated with bone marrow transplants is thought to contraindicate the use of this experimental treatment for HIV-positive individuals without leukemia or lymphoma. Some researchers such as Edward Berger believe that resistance to CCR5 inhibition may emerge if
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 ...
strains of HIV emerge (these use CXCR4 rather than CCR5 as a coreceptor, from which they become independent). Before the treatment though the patient had low levels of the CXCR4 virus but after the treatment this type of HIV could not be detected either which Hütter called "very surprising". People without CCR5 can be more sensitive to some infections such as
West Nile virus West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family ''Flaviviridae'', from the genus ''Flavivirus'', which also contains the Zika virus, dengue virus, and yellow fever virus. The virus ...
. Jay Levy, one of the first researchers to isolate and describe HIV in the early 1980s, wrote an editorial accompanying Hütter's publication in the ''New England Journal of Medicine''. Noting the reduction in detectable HIV in the patient's blood and the return of the patient's circulating CD4+ T-cell population to normal levels, with all of the cells expressing the resistant variant of CCR5, Levy cautions that calling this treatment a cure would be premature. This is because HIV is known to hide in latent form in a variety of organs not easily sampled, including the heart and brain. The high risks of a bone marrow transplant also make this treatment risky since many bone marrow patients die. And the CXCR4 virus that was detectable in the blood of the patient before the treatment "could eventually emerge". Levy does believe though that this case "could pave the way for innovative approaches that provide long-lasting viral control with limited toxicities for persons with HIV infection". As of June 4, 2010, Hütter's patient was in very good health and had been HIV- and cancer-free (combined) for two years. In the March 10, 2011, issue of the medical journal ''
Blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
'', Hütter wrote, "it is reasonable to conclude that cure of HIV infection has been achieved in this patient." Hütter concurred with this assessment. Hütter received an award on June 3, 2010, from the AIDS Policy Project, a national advocacy group focused on an AIDS cure, and San Francisco Supervisor
Ross Mirkarimi Rostam Mirkarimi (born August 4, 1961) is an American politician and the former sheriff of San Francisco. Prior to being sheriff, he served on the San Francisco Board of Supervisors, where he represented District 5. Mirkarimi is a co-founder ...
on behalf of the people of San Francisco. The text read:
"Dr. Gero Hütter: In recognition of your historic achievement of being the first doctor to functionally cure AIDS/HIV through an innovative procedure that entails a remarkable example of the use of stem cell transplants. We join you with hope that your achievement will globally inspire researchers to explore new techniques and technologies for an AIDS cure. On behalf of the people of San Francisco, the AIDS Policy Project, and all those engaged in the combat against the HIV disease, the City and County of San Francisco extends its highest commendation!" —Supervisor Ross Mirkarimi, Member, San Francisco Board of Supervisors, June 3, 2010


See also

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Gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...


References

{{DEFAULTSORT:Hutter, Gero German hematologists HIV/AIDS researchers German medical researchers 1968 births Living people Physicians of the Charité