Researchers are closer to unraveling the mystery of Timothy Ray Brown, the only human cured of HIV, the virus defeated , according to a new study. Although the work does not provide a definitive answer, it excludes a possible explanation.
Brown remains one of the most studied case in the history of the HIV epidemic. In 06, after living with the virus for 11 years and control its infection with antiretroviral drugs (ARVs), he learned he had developed acute myelogenous leukemia. (Leukemia has no known relation to infection or HIV treatment.) The chemotherapy has failed, and the following year Brown, an American who lived in Berlin, received the first of two grafts has the common bone marrow treatment for cancer and has abandoned its ARVs. When people with HIV stop taking ARVs, HIV levels go up arrow usually within weeks. Yet researchers scouring the Brown's blood over the last 7 years have found that traces of viral genetic material, none can replicate.
Today, the researchers point out three factors that might independently or in combination have rid the body of HIV Brown. The first is the conditioning process, in which doctors destroyed the Brown immune system with chemotherapy and whole body irradiation to prepare him for his bone marrow transplant. His oncologist, Gero Hütter, who was then at the Free University of Berlin, also took an additional step that he thought might not just cure leukemia, but also help rid the body of HIV Brown. He found a bone marrow donor that has a rare mutation in a gene which paralyzes a key receptor on white blood cells of the virus uses to establish an infection. (For years, conscripts researchers Brown as the "Berlin patient".) The third possibility is his new immune system attacks the remains of his former which held cells infected with HIV, a process known as the graft against the host.
in the new study, a team led by immunologist Guido Silvestri of Emory University in Atlanta, developed a rare monkey experiment to test these possibilities.
bone marrow transplants work because of stem cells. Modern techniques effectively avoid sucking the bone marrow, and instead can sift through blood and pull the stem cells needed for transplantation to "graft". Thus, the researchers first drew blood from three rhesus macaque monkeys, removed the stem cells, and put them in storage cells. They were then infected animals and these three control monkeys with a hybrid virus, known under the name SHIV, which contains part of the human and simian AIDS virus. The six animals soon started receiving ARVs (which better meet SHIVs that SIV itself), and SHIV levels in the blood quickly dropped below the level of detection on standard tests as planned.
A few months later, the three monkeys who had stored stem cells underwent whole body irradiation to condition their bodies and had their own reinfused stem cells. After the grafted cells, a process that took a few months longer, the researchers stopped the ARV in the three animals and three controls. SHIV quickly came screaming back in the three controls and two transplanted animals. (A transplanted monkeys did not have the virus rebound, but his kidneys have failed and the researchers euthanized.)
The team, who published their work online in PLoS Pathogens today, concludes that conditioned by itself is not likely to rid the body of the AIDS virus. Silvestri explained that the monkey study was a validation of experience principle strictly isolated the effects of single package. "There is no way to do this in humans," he said.
"This is an important study, and it is a very useful model," said Daniel Kuritzkes of Brigham & Women's Hospital in Cambridge, Massachusetts, who was not connected to the research.
Kuritzkes and his colleagues are particularly interested in the experience because two of their own patients infected with leukemia HIV received bone marrow transplants from donors who do not have cells resistant to HIV. for several months after discontinuation of ART, HIV has remained distance in men, raising hopes that resistant donor cells are not a factor. but the virus eventually returned in each patient. Kuritzkes suspect transplants have reduced the amount of HIV left in body-experienced patients under the name viral reservoir, but the virus has resurfaced because he continued to copy and finally overwhelmed the immune responses against him.
Although the study shows that the packaging itself probably can not eliminate HIV infection, the study leaves open the possibility that the disease of the graft against the host played a central role in Brown's healing. Unlike Kuritzkes Brown and two patients, the transplanted monkeys received their own stem cells, which do not trigger a response of the graft against the host. "At the end of the day, which could be an important element," says Silvestri. He also thought it could help reduce the size of the reservoir for treating monkeys with ARVs for more than a few months.
Silvestri hopes to make future monkey experiments that test the different variables, including the transplantation of the animals with the viral blood resistant cells that mimic those that Brown received. "the best scientific studies raise as many questions as answers to that," Steven said Deeks, researcher and clinician at the University of California, San Francisco, who has treated and studied Brown. "Unfortunately, the heroic efforts that went into this study failed to provide a definitive answer regarding the patient's enigmas of Berlin. The model will probably need to be optimized, and at the very least, macaques treated with antiretroviral therapy for longer periods of time. But I am convinced that the team will understand it "
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