Berlin patient, standing alone, continues to prompt questions, search for answers

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CIDWhat happened to Timothy Ray Brown was almost serendipitous, coming as it did from a combination of knowledge, opportunity and readiness. Although what he went through nearly killed him, he remains singularly fortunate. Today, after a year of disappointing news from some on the front lines of HIV cure research, the information gleaned from his case continues to inspire avenues of exploration.

It’s more than seven years now since Brown, the “Berlin patient”  took his last antiretroviral pill, and while some tests show remaining evidence of the HIV infection with which he was diagnosed in 1995, he shows no signs of replicable virus, and he is considered cured. There he still stands alone, a little more than a year after HIV rebounded in two Boston patients who also had undergone similar stem cell transplants, and about half a year since the virus rebounded in the Mississippi baby doctors had hoped was rid of the virus through early and aggressive treatment. While scientists knew that all of the steps that led to Brown’s cure could not be repeated on any significant scale, an article in the January 15 Clinical Infectious Diseases tells how researchers hope to use knowledge yielded by the components of his treatment for leukemia through collaboration between HIV and transplantation specialists. The article recounts some of the ideas discussed at an National Institute of Allergy and Infectious Diseases workshop last February.

When three courses of chemotherapy failed to put his leukemia into remission in 2007, Brown became a candidate for a transplant of stem cells collected from a donor’s bone marrow to replace his own. Selected from more than 200 potential donors, Brown’s donor was one of the only 1 percent of those of European descent with a cell mutation that creates immunity to HIV. Brown underwent the procedure twice, using the same donor when his leukemia returned after the first. While hidden reservoirs of HIV in patients whose virus has been controlled through medication mean the virus will emerge and rebound when treatment has stopped, Brown has been free of both leukemia and replicable HIV since the second procedure.

Researchers are continuing to explore the role of the total body irradiation used to wipe out his own immune system, the donated cells’ attack on his cells — known as graft-versus-host disease — as well as the mutation that kept the donor’s cells from receiving the virus. By discovering how to use those factors to deplete HIV reservoirs, they still hope to duplicate Brown’s cure in other patients requiring transplants, and, should that be possible, learn if the knowledge can be applied more generally.




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