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A Modern Day Medical Miracle

Who hasn’t heard of the biggest demon in modern medicine-HIV? The first cases of AIDS were reported in the United States 37 years ago. Since then, >77 million people have been infected worldwide, resulting in over 35 million deaths. Currently, there are 36.9 million people living with human immunodeficiency virus (HIV), 1.8 million new infections, and nearly 1 million AIDS-related deaths annually.


HIV is one of the most extensively studied viruses in history, and numerous extraordinary scientific advances, including an in-depth understanding of viral biology, pathogenesis, and life-saving antiretroviral therapies, have resulted from investments in HIV/AIDS research. Through constant undying efforts of doctors and scientists worldwide the lives of people living with HIV have been transformed by the current availability of >30 antiretroviral drugs and major strides are being made in the quest for a safe and effective HIV vaccine. The positive impact has ranged from innovations in basic immunology to treatments for immune-mediated diseases and cancer.



Congenital immunodeficiencies have been described as “experiments of nature,” whereby a specific defect in a single component of the complex immune system sheds light on the entire system. Such is the case with AIDS, this acquired syndrome wreaked havoc and exposed how a subcellular creature can bring earth’s supreme being to its knees.


Timothy Ray Brown, a Seattle native gained world renown in 2010 when he revealed his identity as the first person ever to be cured of HIV/AIDS. “He was such a symbol of hope for so many people living with HIV and an inspiration for those of us working toward a cure,” said Fred Hutchinson Cancer Research Centre virologist Dr. Keith Jerome, who got to know Brown in the course of his ongoing research to replicate that cure for others through genetic engineering of immune cells.


Ironically, it was a bid to stop Brown’s cancer that led to a transplant of blood-forming stem cells in 2007 that also cured him of HIV. In the two successive transplants needed to halt his acute myeloid leukemia, Brown received stem cells from a donor who carried a mutation known to confer natural resistance to HIV.


Brown often referred to the time of his transplant as his “new birthdate,”.In November, Kiem, co-founder of “defeatHIV” and Fred Hutch transplant physician, delivered a TEDx talk in Seattle describing how Timothy Ray Brown has inspired his work to find a cure for HIV through the eventual delivery of “gene therapy in a syringe.”




Despite numerous efforts to duplicate Brown’s cure, for a dozen years he remained the only person on Earth known to have beaten the virus. It was his fervent wish to not be the only one…. And his efforts paid off, joining Brown in this elite circle of those thought cured of is Adam Castillejo, a 40-year-old immigrant from Venezuela who worked as a sous chef in London and Loreen Willenberg, a 66-year-old California woman believed to be the first to clear the virus without a transplant or drugs.


It was Timothy’s German oncologist, Dr. Gero Hütter who had proposed to Brown the radical option: If he could find matching blood stem cells from a donor who carried a rare mutation that conferred resistance against HIV, he might be cured of HIV as well as of his leukemia.


German hematologist Dr. Gero Hütter (left) with Timothy Ray Brown (right)


Surprisingly, Brown’s tissue type matched with 267 possible donors, and when Hütter screened the 61st, he found one who also carried two copies of the so-called CCR5 delta 32 mutation. That missing strip of DNA code essentially disables a normal protein on the surface of immune cells that HIV uses like a trap door to break in. Once inside, it hijacks the genetic machinery of these cells to make copies of itself.


Brown was 40 years old when he underwent the first of two transplants of blood-forming stem cells that carried the mutation, and he tested free of HIV ever since. It took a second, grueling transplant a year later to arrest his leukemia.


“Timothy used these years since his diagnosis not only for his own purposes, but as hope and inspiration for all people living with HIV. He did this in his own style: excited, friendly, warm-hearted and well-informed,” Hütter wrote.


Brown moved back to the U.S. shortly after . He continued to participate in HIV cure research, working with scientists still trying to puzzle out why the transplants worked for him. Unfortunately on 29th September 2020 brown succumbed to his recurring cancer and passed away.




 

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GCMER Team

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