Researchers are closer to unraveling the mystery of how Timothy Ray Brown, the only human cured of HIV,
defeated the virus, according to a new study.
Although the work doesn’t provide a definitive answer, it rules out one possible explanation.
Brown remains one of the most studied cases in the HIV epidemic’s history. In 2006, after living with the virus for 11 years and controlling his infection with antiretroviral drugs (ARVs), he learned that he had developed acute myeloid leukemia.
(The leukemia has no known relationship to HIV infection or treatment.) Chemotherapy failed, and the next year Brown, an American then living in Berlin, received the first of two bone marrow transplants a common treatment for this cancer and ditched his ARVs.
When HIV-infected people stop taking ARVs, levels of HIV typically skyrocket within weeks.
Yet researchers scouring Brown’s blood over the past 7 years have found only traces of the viral genetic material, none of which can replicate.
Today, researchers point to three different factors that could independently or in combination have rid Brown’s body of HIV.
The first is the process of conditioning, in which doctors destroyed Brown’s own immune system with chemotherapy and whole body irradiation to prepare him for his bone marrow transplant.
His oncologist, Gero Hütter, who was then with the Free University of Berlin, also took an extra step that he thought might not only cure the leukemia but also help rid Brown’s body of HIV.
He found a bone marrow donor who had a rare mutation in a gene that cripples a key receptor on white blood cells the virus uses to establish an infection.
(For years, researchers referred to Brown as “the Berlin patient.”) The third possibility is his new immune system attacked remnants of his old one that held HIV-infected cells, a process known as graft versus host disease.
In the new study, a team led by immunologist Guido Silvestri of Emory University in Atlanta, designed an unusual monkey experiment to test these possibilities.
Bone marrow transplants work because of stem cells. Modern techniques avoid actually aspirating bone marrow, and instead can sift through blood and pluck out the stem cells needed for a transplant to “engraft.”
So the researchers first drew blood from three rhesus macaque monkeys, removed stem cells, and put the cells in storage.
They then infected these animals and three control monkeys with a hybrid virus, known as SHIV, that contains parts of the simian and human AIDS viruses.
All six animals soon began receiving ARVs (which respond better to SHIVs than SIV itself), and SHIV levels in the blood quickly dropped below the level of detection on standard tests, as expected.
A few months later, the three monkeys that had stored stem cells underwent whole body irradiation to condition their bodies and then had their own stem cells reinfused.
After the cells engrafted, a process that took a few more months, the researchers stopped ARVs in the three animals and in the three controls.
SHIV quickly came screaming back in the three controls and two of the transplanted animals. (One of the transplanted monkeys did not have the virus rebound but its kidneys failed and the researchers euthanized it.)
Although the work doesn’t provide a definitive answer, it rules out one possible explanation.
Brown remains one of the most studied cases in the HIV epidemic’s history. In 2006, after living with the virus for 11 years and controlling his infection with antiretroviral drugs (ARVs), he learned that he had developed acute myeloid leukemia.
(The leukemia has no known relationship to HIV infection or treatment.) Chemotherapy failed, and the next year Brown, an American then living in Berlin, received the first of two bone marrow transplants a common treatment for this cancer and ditched his ARVs.
When HIV-infected people stop taking ARVs, levels of HIV typically skyrocket within weeks.
Yet researchers scouring Brown’s blood over the past 7 years have found only traces of the viral genetic material, none of which can replicate.
Today, researchers point to three different factors that could independently or in combination have rid Brown’s body of HIV.
The first is the process of conditioning, in which doctors destroyed Brown’s own immune system with chemotherapy and whole body irradiation to prepare him for his bone marrow transplant.
His oncologist, Gero Hütter, who was then with the Free University of Berlin, also took an extra step that he thought might not only cure the leukemia but also help rid Brown’s body of HIV.
He found a bone marrow donor who had a rare mutation in a gene that cripples a key receptor on white blood cells the virus uses to establish an infection.
(For years, researchers referred to Brown as “the Berlin patient.”) The third possibility is his new immune system attacked remnants of his old one that held HIV-infected cells, a process known as graft versus host disease.
In the new study, a team led by immunologist Guido Silvestri of Emory University in Atlanta, designed an unusual monkey experiment to test these possibilities.
Bone marrow transplants work because of stem cells. Modern techniques avoid actually aspirating bone marrow, and instead can sift through blood and pluck out the stem cells needed for a transplant to “engraft.”
So the researchers first drew blood from three rhesus macaque monkeys, removed stem cells, and put the cells in storage.
They then infected these animals and three control monkeys with a hybrid virus, known as SHIV, that contains parts of the simian and human AIDS viruses.
All six animals soon began receiving ARVs (which respond better to SHIVs than SIV itself), and SHIV levels in the blood quickly dropped below the level of detection on standard tests, as expected.
A few months later, the three monkeys that had stored stem cells underwent whole body irradiation to condition their bodies and then had their own stem cells reinfused.
After the cells engrafted, a process that took a few more months, the researchers stopped ARVs in the three animals and in the three controls.
SHIV quickly came screaming back in the three controls and two of the transplanted animals. (One of the transplanted monkeys did not have the virus rebound but its kidneys failed and the researchers euthanized it.)
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